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Journal of Neurochemistry Nov 2023Psilocybin is the main psychoactive compound found in hallucinogenic/magic mushrooms and can bind to both serotonergic and tropomyosin receptor kinase b (TrkB)... (Review)
Review
Psilocybin is the main psychoactive compound found in hallucinogenic/magic mushrooms and can bind to both serotonergic and tropomyosin receptor kinase b (TrkB) receptors. Psilocybin has begun to show efficacy for a range of neuropsychiatric conditions, including treatment-resistant depression and anxiety disorders; however, neurobiological mechanisms are still being elucidated. Clinical research has found that psilocybin can alter functional connectivity patterns in human brains, which is often associated with therapeutic outcomes. However, preclinical research affords the opportunity to assess the potential cellular mechanisms by which psilocybin may exert its therapeutic effects. Preclinical rodent models can also facilitate a more tightly controlled experimental context and minimise placebo effects. Furthermore, where there is a rationale, preclinical researchers can investigate psilocybin administration in neuropsychiatric conditions that have not yet been researched clinically. As a result, we have systematically reviewed the knowledge base, identifying 82 preclinical studies which were screened based on specific criteria. This resulted in the exclusion of 44 articles, with 34 articles being included in the main review and another 2 articles included as Supporting Information materials. We found that psilocybin shows promise as a lead candidate molecule for treating a variety of neuropsychiatric conditions, albeit showing the most efficacy for depression. We discuss the experimental findings, and identify possible mechanisms whereby psilocybin could invoke therapeutic changes. Furthermore, we critically evaluate the between-study heterogeneity and possible future research avenues. Our review suggests that preclinical rodent models can provide valid and translatable tools for researching novel psilocybin-induced molecular and cellular mechanisms, and therapeutic outcomes.
PubMed: 38019032
DOI: 10.1111/jnc.16017 -
Brain Sciences Jun 2023Around the world, more the 700,000 individuals die by suicide every year. It is necessary to understand the mechanisms associated with suicidal behavior. Recently, an... (Review)
Review
Around the world, more the 700,000 individuals die by suicide every year. It is necessary to understand the mechanisms associated with suicidal behavior. Recently, an increase in gene expression studies has been in development. Through a systematic review, we aimed to find a candidate gene in gene expression studies on postmortem brains of suicide completers. Databases were systematically searched for published studies. We performed an online search using PubMed, Scopus and Web of Science databases to search studies up until May 2023. The terms included were "gene expression", "expressed genes", "microarray", "qRT-PCR", "brain samples" and "suicide". Our systematic review included 59 studies covering the analysis of 1450 brain tissues from individuals who died by suicide. The majority of gene expression profiles were obtained of the prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, ventral prefrontal cortex and orbital frontal cortex area. The most studied mRNAs came of genes in glutamate, γ-amino-butyric acid and polyamine systems. mRNAs of genes in the brain-derived neurotrophic factor, tropomyosin-related kinase B (TrkB), HPA axis and chemokine family were also studied. On the other hand, psychiatric comorbidities indicate that suicide by violent death can alter the profile of mRNA expression.
PubMed: 37371384
DOI: 10.3390/brainsci13060906 -
Brain and Behavior Feb 2023Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment... (Review)
Review
BACKGROUND
Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment is relatively scarce. Hyperalgesia mediated by pro-inflammatory factors and chemokines plays an important role in the occurrence and maintenance of NP.
DATA TREATMENT
Therefore, we conducted a systematic literature review of experimental NP (PubMed Medline), in order to find the mechanism of inducing central sensitization and explore the intervention methods of hyperalgesia caused by real or simulated injury.
RESULT
In this review, we sorted out the activation pathways of microglia, astrocytes and neurons, and the process of crosstalk among them. It was found that in NP, the microglia P2X4 receptor is the key target, which can activate the mitogen-activated protein kinase pathway inward and then activate astrocytes and outwardly activate neuronal tropomyosin receptor kinase B receptor to activate neurons. At the same time, activated neurons continue to maintain the activation of astrocytes and microglia through chemokines on CXCL13/CXCR5 and CX3CL1/CX3CR1. This crosstalk process is the key to maintaining NP.
CONCLUSION
We summarize the further research on crosstalk among neurons, microglia, and astrocytes in the central nervous system, elaborate the ways and connections of relevant crosstalk, and find potential crosstalk targets, which provides a reference for drug development and preclinical research.
Topics: Humans; Hyperalgesia; Neuroglia; Neuralgia; Neurons; Spinal Cord; Microglia; Astrocytes
PubMed: 36602945
DOI: 10.1002/brb3.2868 -
Current Oncology (Toronto, Ont.) Oct 2022Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast... (Review)
Review
Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast cancer is of primary urgency, as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor involved in the regulation of neuronal functions through the binding of the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). In addition, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin, or by binding to TrkA receptors with low affinity. Several examples of in vitro and in vivo evidence show that NGF is both synthesized and released by breast cancer cells, and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. In this paper, we comprehensively summarize and systematically review the current experimental evidence on this topic. INPLASY ID: INPLASY2022100017.
Topics: Female; Humans; Nerve Growth Factor; Receptor, trkA; Breast Neoplasms; Receptor, Nerve Growth Factor; Signal Transduction
PubMed: 36354700
DOI: 10.3390/curroncol29110640 -
Frontiers in Physiology 2022Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca to troponin C relieves this...
Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca to troponin C relieves this inhibition by changing contacts among the regulatory components and ultimately repositioning tropomyosin on the actin filament creating a state that is permissive for contraction. Several lines of evidence suggest that there are three possible positions of tropomyosin on actin commonly called Blocked, Closed/Calcium and Open or Myosin states. These states are thought to correlate with different functional states of the contractile system: inactive-Ca-free, inactive-Ca-bound and active. The inactive-Ca-free state is highly occupied at low free Ca levels. However, saturating Ca produces a mixture of inactive and active states making study of the individual states difficult. Disease causing mutations of troponin, as well as phosphomimetic mutations change the stabilities of the states of the regulatory complex thus providing tools for studying individual states. Mutants of troponin are available to stabilize each of three structural states. Particular attention is given to the hypertrophic cardiomyopathy causing mutation, Δ14 of TnT, that is missing the last 14 C-terminal residues of cardiac troponin T. Removal of the basic residues in this region eliminates the inactive-Ca-free state. The major state occupied with Δ14 TnT at inactivating Ca levels resembles the inactive-Ca-bound state in function and in displacement of TnI from actin-tropomyosin. Addition of Ca, with Δ14TnT, shifts the equilibrium between the inactive-Ca-bound and the active state to favor that latter state. These mutants suggest a unique role for the C-terminal region of Troponin T as a brake to limit Ca activation.
PubMed: 35694406
DOI: 10.3389/fphys.2022.902079 -
European Psychiatry : the Journal of... Nov 2021Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression,...
BACKGROUND
Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share.
METHODS
We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms.
RESULTS
Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms.
CONCLUSIONS
Further studies should investigate mental disorders and chronic skin diseases concurrently across patients' life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.
Topics: Animals; Anxiety; Catechol O-Methyltransferase; Comorbidity; Depression; Dermatitis, Atopic; Hidradenitis Suppurativa; Humans; Psoriasis; Quality of Life
PubMed: 34819201
DOI: 10.1192/j.eurpsy.2021.2249 -
[Primary small cell neuroendocrine carcinoma of the larynx: a review of literature and case series].Laryngo- Rhino- Otologie Dec 2021Small cell neuroendocrine carcinoma (SCNC) of the larynx is a rare tumor entity with a 5-year overall survival (OS) of only 5 % after treatment with chemoradiotherapy.
INTRODUCTION
Small cell neuroendocrine carcinoma (SCNC) of the larynx is a rare tumor entity with a 5-year overall survival (OS) of only 5 % after treatment with chemoradiotherapy.
METHODS
A systematic review of the literature was performed for "SCNC" and "SCNC in head and neck". Our hospital's own electronic patient file database was investigated for patients diagnosed with a SCNC over the last 12 years.
RESULTS
The effectiveness of chemoradiotherapy in SCNC is still unclear since randomized clinical trials are missing for the evaluation of standard of care treatment. Common therapy approaches are based on experiences with small cell lung cancer. 0.5 % of all SCNC occur in the head and neck region. In the last 12 years, we diagnosed 9 patients with SCNC, two of which were located in the larynx. Exemplarily, we report the case of a 29-year-old male with the initial diagnosis of a SCNC of the larynx with concurrent lymph node metastasis. This case is particularly interesting due to the young age at disease onset and the lack of major risk factors. Treatment was modified to nivolumab due to progressive disease after treatment with chemoradiotherapy. After an OS of 22 months, the patient deceased due to a tumor-associated major bleeding with airway obstruction.
CONCLUSION
So far there are no clinical reports evaluating the use of nivolumab in third-line-therapy of SCNC. NTRK fusion (neurotrophic tyrosine receptor kinase gene fusion) or the folate receptor expression analysis should be considered to evaluate the potential use of a tropomyosin receptor kinase inhibitor or a folate receptor targeting therapy.
Topics: Adult; Antineoplastic Agents; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Humans; Larynx; Male
PubMed: 33395712
DOI: 10.1055/a-1334-4444 -
Journal of the American Heart... Dec 2020Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are... (Meta-Analysis)
Meta-Analysis
Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are subdivided by classic umbrella terms, such as "fibroblasts," "myofibroblasts," "smooth muscle cells," "fibrocytes," "mesangial cells," and "pericytes." However, a discriminative marker-based subclassification has to date not been established. Methods and Results As a first effort toward a classification scheme, a systematic literature search was performed to identify the most commonly used phenotypical and functional protein markers for characterizing and classifying vascular mesenchymal cell subpopulation(s). We next applied immunohistochemistry and immunofluorescence to inventory the expression pattern of identified markers on human aorta specimens representing early, intermediate, and end stages of human atherosclerotic disease. Included markers comprise markers for mesenchymal lineage (vimentin, FSP-1 [fibroblast-specific protein-1]/S100A4, cluster of differentiation (CD) 90/thymocyte differentiation antigen 1, and FAP [fibroblast activation protein]), contractile/non-contractile phenotype (α-smooth muscle actin, smooth muscle myosin heavy chain, and nonmuscle myosin heavy chain), and auxiliary contractile markers (h1-Calponin, h-Caldesmon, Desmin, SM22α [smooth muscle protein 22α], non-muscle myosin heavy chain, smooth muscle myosin heavy chain, Smoothelin-B, α-Tropomyosin, and Telokin) or adhesion proteins (Paxillin and Vinculin). Vimentin classified as the most inclusive lineage marker. Subset markers did not separate along classic lines of smooth muscle cell, myofibroblast, or fibroblast, but showed clear temporal and spatial diversity. Strong indications were found for presence of stem cells/Endothelial-to-Mesenchymal cell Transition and fibrocytes in specific aspects of the human atherosclerotic process. Conclusions This systematic evaluation shows a highly diverse and dynamic landscape for the human vascular mesenchymal cell population that is not captured by the classic nomenclature. Our observations stress the need for a consensus multiparameter subclass designation along the lines of the cluster of differentiation classification for leucocytes.
Topics: Atherosclerosis; Humans; Mesenchymal Stem Cells; Muscle, Smooth, Vascular
PubMed: 33190596
DOI: 10.1161/JAHA.120.017094 -
Oral Surgery, Oral Medicine, Oral... Oct 2021The aim of this systematic review was to describe the epidemiology, diagnostic criteria, differential diagnosis, treatment, prognostic factors, and treatment outcomes of... (Review)
Review
OBJECTIVE
The aim of this systematic review was to describe the epidemiology, diagnostic criteria, differential diagnosis, treatment, prognostic factors, and treatment outcomes of secretory carcinoma.
STUDY DESIGN
A comprehensive search of Lilacs, PubMed, Science Direct, and Web of Science databases was conducted to identify all case reports, letter to the editor, and histopathologic reclassifications regarding salivary gland secretory carcinoma published in English, Spanish, French, and Portuguese.
RESULTS
The final analysis included 119 studies, which totaled 642 secretory carcinoma diagnoses, with 239 case reports and 403 diagnostic reclassifications, mostly in the United States. The age range was 5 to 87 years, and cases were predominantly in males (58.7%) and mostly affecting the parotid glands (73.7%). The disease usually presents as a slow-growing, painless mass. The main differential diagnosis is acinic cell carcinoma, and the tumor is usually treated with surgery. The prognosis is considered favorable, although there have been reports of local recurrences, distant metastases, and deaths.
CONCLUSIONS
It is important that clinicians become aware of this salivary gland neoplasm and report clinical data, clinical course, management and long-term follow-up. There is an urgent need to conduct more clinical trials, especially on tropomyosin receptor kinase (TRK) inhibitors and other potential target therapy modalities.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Acinar Cell; Child; Child, Preschool; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Salivary Gland Neoplasms; Salivary Glands; Young Adult
PubMed: 32493686
DOI: 10.1016/j.oooo.2020.04.007 -
Future Oncology (London, England) Feb 2020To conduct a systematic review and meta-analysis feasibility of clinical, quality of life and economic evidence for neurotrophic tropomyosin-related receptor tyrosine... (Meta-Analysis)
Meta-Analysis
To conduct a systematic review and meta-analysis feasibility of clinical, quality of life and economic evidence for neurotrophic tropomyosin-related receptor tyrosine kinases () inhibitors in patients with gene fusion-positive tumors. Databases were searched for studies on inhibitors in adult and pediatric patients. 27 publications reported clinical data for seven interventions. Efficacy/safety data were available for two interventions only. Four trials each reported data for larotrectinib and entrectinib with pooled analyses reporting objective response rates of 75% (95% CI: 61-85) and 57.4% (43.2-70.8), respectively. No publications reported economic or quality of life evidence. Preliminary data demonstrate that inhibitors are well tolerated and show impressive clinical benefit; corroboration of existing studies and real-world data are required.
Topics: Antineoplastic Agents; Disease Management; Humans; Neoplasms; Oncogene Proteins, Fusion; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Quality of Life; Treatment Outcome; Tropomyosin
PubMed: 31942815
DOI: 10.2217/fon-2019-0534