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Analytical Cellular Pathology... 2023Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous... (Review)
Review
Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous system (CNS). The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS-CoV-2 infection and neurological manifestations. This study aimed to present an updated review of the role of brain RAS components, especially ACE2, in neurological complications induced by SARS-CoV-2 infection. Several routes of SARS-CoV-2 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID-19 patients, the olfactory nerve route was suggested as an early pathway for SARS-CoV-2 entry into the brain. In addition, a hematogenous route via disintegrations in the blood-brain barrier following an increase in systemic cytokine and chemokine levels and retrograde axonal transport, especially via the vagus nerve innervating lungs, have been described. Common nonspecific neurological symptoms in COVID-19 patients are myalgia, headache, anosmia, and dysgeusia. However, more severe outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, and stroke. Alterations in brain RAS components such as angiotensin II (Ang II) and ACE2 mediate neurological manifestations of SARS-CoV-2 infection, at least in part. Downregulation of ACE2 due to SARS-CoV-2 infection, followed by an increase in Ang II levels, leads to hyperinflammation and oxidative stress, which in turn accelerates neurodegeneration in the brain. Furthermore, ACE2 downregulation in the hypothalamus induces stress and anxiety responses by increasing corticotropin-releasing hormone. SARS-CoV-2 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID-19. It can be concluded that the neurological manifestations of COVID-19 may be partially associated with changes in brain RAS components.
Topics: Humans; SARS-CoV-2; COVID-19; Renin-Angiotensin System; Angiotensin-Converting Enzyme 2; Peptidyl-Dipeptidase A; Anosmia; Brain
PubMed: 37575318
DOI: 10.1155/2023/8883492 -
Alternative Therapies in Health and... Oct 2023The rapid global emergence of distortions of the senses of smell and taste consequential to COVID-19 has provoked an unprecedented demand for investigation into...
The rapid global emergence of distortions of the senses of smell and taste consequential to COVID-19 has provoked an unprecedented demand for investigation into treatments capable of addressing such medical phenomena. While the pandemic's principal focus rests on interventions intended to prevent the infection and its spread, much attention must be devoted to amelioration of these common symptomatic sequelae of it. The medical historical record reveals a shocking paucity of serious consideration of olfactory and gustatory dysfunction (OGD), hardly exclusive to SARS-CoV-2 infection (as discussed in Part 1 of this article series). To date, no treatment approach has ever delivered noteworthy clinical results for chronic cases. Numerous studies and reviews have addressed the epidemiology and hypotheses of OGD pathophysiology. Past and recent studies have produced vague findings and conclusions devoid of practical clinical applications for patients who continue to experience chronic sensory distortions and deficits. It is urgent that focused exploration be aggressively pursued for therapeutic and restorative modalities to ameliorate OGD across all medical disciplines, with no bias towards any one approach. It is imperative that approaches outside the pharmacological realm are studied; no effective medication of any merit exists. Thus, innovative and new approaches potentially capable of supporting natural self-regulation and restoration of healthy neurophysiology must be investigated, post-haste. Specifically, stimulation of cranial nerves via their auricular branches, by means of various modalities, may hold promise. A vast body of evidence exists to support its investigation. Its inclusion as an extremely safe and inexpensive approach to endeavor to resolve chronic OGD (not merely for post-COVID19 infection) is warranted. The 3-phase auricular acupuncture microsystem may be the most precise form of targeting and positively influencing specific neurological structures affected by COVID-19.
PubMed: 37573588
DOI: No ID Found -
Sensors (Basel, Switzerland) May 2023In order to advance the development of sensors fabricated with monofunctional sensation systems capable of a versatile response to tactile, thermal, gustatory,...
In order to advance the development of sensors fabricated with monofunctional sensation systems capable of a versatile response to tactile, thermal, gustatory, olfactory, and auditory sensations, mechanoreceptors fabricated as a single platform with an electric circuit require investigation. In addition, it is essential to resolve the complicated structure of the sensor. In order to realize the single platform, our proposed hybrid fluid (HF) rubber mechanoreceptors of free nerve endings, Merkel cells, Krause end bulbs, Meissner corpuscles, Ruffini endings, and Pacinian corpuscles mimicking the bio-inspired five senses are useful enough to facilitate the fabrication process for the resolution of the complicated structure. This study used electrochemical impedance spectroscopy (EIS) to elucidate the intrinsic structure of the single platform and the physical mechanisms of the firing rate such as slow adaption (SA) and fast adaption (FA), which were induced from the structure and involved the capacitance, inductance, reactance, etc. of the HF rubber mechanoreceptors. In addition, the relations among the firing rates of the various sensations were clarified. The adaption of the firing rate in the thermal sensation is the opposite of that in the tactile sensation. The firing rates in the gustation, olfaction, and auditory sensations at frequencies of less than 1 kHz have the same adaption as in the tactile sensation. The present findings are useful not only in the field of neurophysiology, to research the biochemical reactions of neurons and brain perceptions of stimuli, but also in the field of sensors, to advance salient developments in sensors mimicking bio-inspired sensations.
Topics: Smell; Rubber; Touch; Mechanoreceptors; Thermosensing
PubMed: 37430506
DOI: 10.3390/s23104593 -
Acta Gastro-enterologica Belgica 2023A 69-year-old male with a past medical history of an Olfactory nerve meningioma and left-sided Bell's palsy presented with 6 weeks of lower abdominal pain and weight...
A 69-year-old male with a past medical history of an Olfactory nerve meningioma and left-sided Bell's palsy presented with 6 weeks of lower abdominal pain and weight loss of 4 kg in 6 months. His current medications included acetylsalicylic acid 80 mg once daily, Amlodipine 5 mg once daily and Allopurinol 300 mg once daily. Physical examination was benign without signs of acute abdomen. The abdomen was nondistended and soft but tender to palpation over the left lower quadrant. Laboratory studies showed no acute outliers. The patient was followed up by his pulmonologist because of thoracic lesions which required a PET-CT for further evaluation. This PET-CT revealed a focal zone of oedematous rectosigmoid colon with a strong suspicion of a semi-circular sigmoid neoplasia with continuation to the bladder (Figure 1a). A presumptive diagnosis of a primary colonic malignancy was made. Colonoscopy was performed and visualised a foreign linear object lodged in both walls of the diverticular sigmoid with surrounding inflammation, but otherwise normal mucosa (Figure 1b). No arguments could be made endoscopically to support the diagnosis of an underlying primary colonic malignancy.
Topics: Male; Humans; Aged; Positron Emission Tomography Computed Tomography; Colon, Sigmoid; Colonoscopy; Colonic Neoplasms
PubMed: 37428178
DOI: 10.51821/86.2.11927 -
Biological Psychology Sep 2023Each organism must regulate its internal state in a metabolically efficient way as it interacts in space and time with an ever-changing and only partly predictable... (Review)
Review
Each organism must regulate its internal state in a metabolically efficient way as it interacts in space and time with an ever-changing and only partly predictable world. Success in this endeavor is largely determined by the ongoing communication between brain and body, and the vagus nerve is a crucial structure in that dialogue. In this review, we introduce the novel hypothesis that the afferent vagus nerve is engaged in signal processing rather than just signal relay. New genetic and structural evidence of vagal afferent fiber anatomy motivates two hypotheses: (1) that sensory signals informing on the physiological state of the body compute both spatial and temporal viscerosensory features as they ascend the vagus nerve, following patterns found in other sensory architectures, such as the visual and olfactory systems; and (2) that ascending and descending signals modulate one another, calling into question the strict segregation of sensory and motor signals, respectively. Finally, we discuss several implications of our two hypotheses for understanding the role of viscerosensory signal processing in predictive energy regulation (i.e., allostasis) as well as the role of metabolic signals in memory and in disorders of prediction (e.g., mood disorders).
Topics: Humans; Vagus Nerve; Afferent Pathways; Allostasis
PubMed: 37419401
DOI: 10.1016/j.biopsycho.2023.108626 -
Science Advances Jul 2023Oxygen (O) sensing by the carotid body is critical for maintaining cardiorespiratory homeostasis during hypoxia. Hydrogen sulfide (HS) signaling is implicated in carotid...
Oxygen (O) sensing by the carotid body is critical for maintaining cardiorespiratory homeostasis during hypoxia. Hydrogen sulfide (HS) signaling is implicated in carotid body activation by low O. Here, we show that persulfidation of olfactory receptor 78 (Olfr78) by HS is an integral component of carotid body activation by hypoxia. Hypoxia and HS increased persulfidation in carotid body glomus cells and persulfidated cysteine in Olfr78 protein in heterologous system. mutants manifest impaired carotid body sensory nerve, glomus cell, and breathing responses to HS and hypoxia. Glomus cells are positive for G adenylate cyclase 3 (Adcy3) and cyclic nucleotide-gated channel alpha 2 (Cnga2), key molecules of odorant receptor signaling. or mutants exhibited impaired carotid body and glomus cell responses to HS and breathing responses to hypoxia. These results suggest that HS through redox modification of Olfr78 participates in carotid body activation by hypoxia to regulate breathing.
Topics: Humans; Receptors, Odorant; Hypoxia; Hydrogen Sulfide; Carotid Body; Oxygen
PubMed: 37406126
DOI: 10.1126/sciadv.adf3026 -
Journal of Neurological Surgery. Part... Aug 2023The endoscopic-assisted supraorbital approach (eSOA) constitutes a minimally invasive strategy for removing anterior skull base meningiomas (ASBM). We present the...
The endoscopic-assisted supraorbital approach (eSOA) constitutes a minimally invasive strategy for removing anterior skull base meningiomas (ASBM). We present the largest retrospective single-institution and long-term follow-up study of eSOA for ASBM resection, providing further insight regarding indication, surgical considerations, complications, and outcome. We evaluated data of 176 patients operated on ASBM via the eSOA over 22 years. Sixty-five tuberculum sellae (TS), 36 anterior clinoid (AC), 28 olfactory groove (OG), 27 planum sphenoidale, 11 lesser sphenoid wing, seven optic sheath, and two lateral orbitary roof meningiomas were assessed. Median surgery duration was 3.35 ± 1.42 hours, being significantly longer for OG and AC meningiomas ( <0.05). Complete resection was achieved in 91%. Complications included hyposmia (7.4%), supraorbital hypoesthesia (5.1%), cerebrospinal fluid fistula (5%), orbicularis oculi paresis (2.8%), visual disturbances (2.2%), meningitis (1.7%) and hematoma and wound infection (1.1%). One patient died due to intraoperative carotid injury, other due to pulmonary embolism. Median follow-up was 4.8 years with a tumor recurrence rate of 10.8%. Second surgery was chosen in 12 cases (10 via the previous SOA and two via pterional approach), whereas two patients received radiotherapy and in five patients a wait-and-see strategy was adopted. The eSOA represents an effective option for ASBM resection, enabling high complete resection rates and long-term disease control. Neuroendoscopy is fundamental for improving tumor resection while reducing brain and optic nerve retraction. Potential limitations and prolonged surgical duration may arise from the small craniotomy and reduced maneuverability, especially for large or strongly adherent lesions.
PubMed: 37405235
DOI: 10.1055/s-0042-1751000 -
Biomedicine & Pharmacotherapy =... Sep 2023Cell transplantation using olfactory ensheathing cells (OECs) is a promising approach for nerve repair but there are numerous limitations with their delivery method....
Cell transplantation using olfactory ensheathing cells (OECs) is a promising approach for nerve repair but there are numerous limitations with their delivery method. Three-dimensional (3D) cell culture systems potentially offer a powerful approach for cell production and delivery options. To further optimise the use of OECs, strategies to promote cell viability and maintain cell behaviours in 3D cultures become important. We previously demonstrated an anti-diabetic drug, liraglutide, could modulate OEC migration and re-model extracellular matrix in two-dimensional (2D) cultures. In the present study, we further investigated its beneficial effects in our 3D culture system using primary OECs. OECs treated with liraglutide at 100 nM showed improved cell viability and had modulated expression of N-cadherin and β1-integrin (two important cell adhesion molecules). When formed into 3D spheroids, the pre-treated OECs generated spheroids with an increased volume and a decreased cell density compared to control spheroids. OECs that subsequently migrated out of the liraglutide pre-treated spheroids had higher capacity for migration with increased duration and length, which was attributed to a reduction in the pauses during the migration. Moreover, OECs that migrated out from liraglutide spheroids had a more bipolar morphology consistent with higher migratory capacity. In summary, liraglutide improved the viability of OECs, modulated cell adhesion molecules, and resulted in stable 3D cell constructs which conferred enhanced migratory capacity on the OECs. Overall, liraglutide may potentially improve the therapeutic use of OECs for neural repair by enhancing the generation of stable 3D constructs and increasing the migratory behaviour of OECs.
Topics: Cells, Cultured; Liraglutide; Olfactory Bulb; Cell Adhesion Molecules; Neuroglia
PubMed: 37399717
DOI: 10.1016/j.biopha.2023.115084