scholarly journals The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

2020 ◽  
Vol 22 (1) ◽  
pp. 373
Author(s):  
Wu Jeong Hwang ◽  
Tae Young Lee ◽  
Nahrie Suk Kim ◽  
Jun Soo Kwon
Keyword(s):  
Estrogen Receptors ◽  
Psychiatric Disorders ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Estrogen Signaling ◽  
Brain Functions ◽  
Wide Range ◽  
Novel Treatment Strategies ◽  
Future Direction ◽  
Preclinical And Clinical Studies

Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.

scholarly journals Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms

2020 ◽  
pp. 972-987
Author(s):  
Ramez N. Eskander ◽  
Julia Elvin ◽  
Laurie Gay ◽  
Jeffrey S. Ross ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Current Treatment ◽  
High Grade ◽  
Novel Treatment ◽  
Sample Average ◽  
Genomic Landscape ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Sample Range ◽  
Novel Treatment Strategies

PURPOSE High-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape. PATIENTS AND METHODS Ninety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs. RESULTS The median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors ( P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found. CONCLUSION This large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.

scholarly journals Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

Metabolites ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 72 ◽  
Author(s):  
Elke Humer ◽  
Thomas Probst ◽  
Christoph Pieh
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Treatment Strategies ◽  
Mood Stabilizers ◽  
Psychiatric Medication ◽  
Mitochondrial Regulation ◽  
Novel Treatment Strategies ◽  
Insight Into ◽  
Test Treatment

Biomarkers are a recent research target within biological factors of psychiatric disorders. There is growing evidence for deriving biomarkers within psychiatric disorders in serum or urine samples in humans, however, few studies have investigated this differentiation in brain or cerebral fluid samples in psychiatric disorders. As brain samples from humans are only available at autopsy, animal models are commonly applied to determine the pathogenesis of psychiatric diseases and to test treatment strategies. The aim of this review is to summarize studies on biomarkers in animal models for psychiatric disorders. For depression, anxiety and addiction disorders studies, biomarkers in animal brains are available. Furthermore, several studies have investigated psychiatric medication, e.g., antipsychotics, antidepressants, or mood stabilizers, in animals. The most notable changes in biomarkers in depressed animal models were related to the glutamate-γ-aminobutyric acid-glutamine-cycle. In anxiety models, alterations in amino acid and energy metabolism (i.e., mitochondrial regulation) were observed. Addicted animals showed several biomarkers according to the induced drugs. In summary, animal models provide some direct insights into the cellular metabolites that are produced during psychiatric processes. In addition, the influence on biomarkers due to short- or long-term medication is a noticeable finding. Further studies should combine representative animal models and human studies on cerebral fluid to improve insight into mental disorders and advance the development of novel treatment strategies.

scholarly journals Novel Therapies for Relapsed and Refractory Neuroblastoma

Children ◽  
2018 ◽  
Vol 5 (11) ◽  
pp. 148 ◽  
Author(s):  
Peter Zage
Keyword(s):  
Clinical Trials ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Disease Relapse ◽  
Therapeutic Modalities ◽  
Treatment Regimens ◽  
Novel Treatment ◽  
Improved Outcomes ◽  
Outcomes For Children ◽  
Novel Treatment Strategies

While recent increases in our understanding of the biology of neuroblastoma have allowed for more precise risk stratification and improved outcomes for many patients, children with high-risk neuroblastoma continue to suffer from frequent disease relapse, and despite recent advances in our understanding of neuroblastoma pathogenesis, the outcomes for children with relapsed neuroblastoma remain poor. These children with relapsed neuroblastoma, therefore, continue to need novel treatment strategies based on a better understanding of neuroblastoma biology to improve outcomes. The discovery of new tumor targets and the development of novel antibody- and cell-mediated immunotherapy agents have led to a large number of clinical trials for children with relapsed neuroblastoma, and additional clinical trials using molecular and genetic tumor profiling to target tumor-specific aberrations are ongoing. Combinations of these new therapeutic modalities with current treatment regimens will likely be needed to improve the outcomes of children with relapsed and refractory neuroblastoma.

scholarly journals SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Henk Scheper ◽  
Julia M. Wubbolts ◽  
Joanne A. M. Verhagen ◽  
Adriëtte W. de Visser ◽  
Robert J. P. van der Wal ◽  
...  
Keyword(s):  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Treatment Strategies ◽  
Antibacterial Activities ◽  
Current Treatment ◽  
Log Reduction ◽  
Prosthetic Joint ◽  
Novel Treatment Strategies ◽  
Titanium Aluminium

Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.

Metabolic Syndrome is a Risk Factor for Post-Operative Adhesions: Need for Novel Treatment Strategies

2018 ◽  
Vol 51 (01) ◽  
pp. 35-41 ◽  
Author(s):  
Yair Pilpel ◽  
Guy Pines ◽  
Andreas Birkenfeld ◽  
Stefan Bornstein ◽  
Rafael Miller
Keyword(s):  
Metabolic Syndrome ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Postoperative Adhesions ◽  
Invasive Procedures ◽  
Novel Treatment ◽  
Number Of Patients ◽  
Wide Range ◽  
Novel Treatment Strategies

AbstractMetabolic syndrome is a group of disorders which include obesity, diabetes, dyslipidemias, and hypertension. This condition is rapidly increasing in an aging population. The rates of surgery in older patients is also growing and a wide range of operations including minimally invasive procedures is now available for this segment of the population. The number of patients suffering from postoperative adhesions is therefore correspondingly increasing. In addition to preventing and treating the metabolic disease itself, improved therapeutic strategies for the prevention of surgical adhesions have to be developed. Here we review the existing and novel treatment options.

scholarly journals Modulating Neuroinflammation to Treat Neuropsychiatric Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-21 ◽  
Author(s):  
Franziska A. Radtke ◽  
Gareth Chapman ◽  
Jeremy Hall ◽  
Yasir A. Syed
Keyword(s):  
Psychiatric Disorders ◽  
Cognitive Deficits ◽  
Inflammatory Responses ◽  
Copy Number Variants ◽  
Treatment Strategies ◽  
Behavioral Responses ◽  
Neuropsychiatric Disorders ◽  
Current Therapies ◽  
Preclinical And Clinical Studies

Neuroinflammation is recognised as one of the potential mechanisms mediating the onset of a broad range of psychiatric disorders and may contribute to nonresponsiveness to current therapies. Both preclinical and clinical studies have indicated that aberrant inflammatory responses can result in altered behavioral responses and cognitive deficits. In this review, we discuss the role of inflammation in the pathogenesis of neuropsychiatric disorders and ask the question if certain genetic copy-number variants (CNVs) associated with psychiatric disorders might play a role in modulating inflammation. Furthermore, we detail some of the potential treatment strategies for psychiatric disorders that may operate by altering inflammatory responses.

scholarly journals Retinal organoids as models for development and diseases

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiao Zhang ◽  
Wen Wang ◽  
Zi-Bing Jin
Keyword(s):  
Disease Model ◽  
Three Dimensional ◽  
Treatment Strategies ◽  
Disease Process ◽  
Retinal Disease ◽  
Current Treatment ◽  
Clear Understanding ◽  
Retinal Diseases ◽  
Developmental Studies ◽  
Novel Treatment Strategies

AbstractThe evolution of pluripotent stem cell-derived retinal organoids (ROs) has brought remarkable opportunities for developmental studies while also presenting new therapeutic avenues for retinal diseases. With a clear understanding of how well these models mimic native retinas, such preclinical models may be crucial tools that are widely used for the more efficient translation of studies into novel treatment strategies for retinal diseases. Genetic modifications or patient-derived ROs can allow these models to simulate the physical microenvironments of the actual disease process. However, we are currently at the beginning of the three-dimensional (3D) RO era, and a general quantitative technology for analyzing ROs derived from numerous differentiation protocols is still missing. Continued efforts to improve the efficiency and stability of differentiation, as well as understanding the disparity between the artificial retina and the native retina and advancing the current treatment strategies, will be essential in ensuring that these scientific advances can benefit patients with retinal disease. Herein, we briefly discuss RO differentiation protocols, the current applications of RO as a disease model and the treatments for retinal diseases by using RO modeling, to have a clear view of the role of current ROs in retinal development and diseases.

scholarly journals Immunomodulation Eliminates Inflammation in the Hippocampus in Experimental Autoimmune Encephalomyelitis, but Does Not Ameliorate Anxiety-Like Behavior

2021 ◽  
Vol 12 ◽  
Author(s):  
Pece Kocovski ◽  
Nuzhat Tabassum-Sheikh ◽  
Stephanie Marinis ◽  
Phuc T. Dang ◽  
Matthew W. Hale ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Treatment Strategies ◽  
The Other ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Other Hand ◽  
Wide Range ◽  
Sphingosine 1 Phosphate ◽  
Novel Treatment Strategies ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system, characterized by an unpredictable disease course and a wide range of symptoms. Emotional and cognitive deficits are now recognized as primary disease manifestations and not simply the consequence of living with a chronic condition, raising questions regarding the efficacy of current therapeutics for these specific symptoms. Mechanisms underlying psychiatric sequelae in MS are believed to be similar to those underlying pathogenesis, that is mediated by cytokines and other inflammatory mediators. To gain insight into the pathogenesis of MS depression, we performed behavioral assays in the murine experimental autoimmune encephalomyelitis (EAE) MS model, in the presence or absence of immunomodulation using the drug FTY720, an analogue of the lipid signaling molecule sphingosine-1-phosphate (S1P). Specifically, mice were challenged with the elevated plus maze (EPM) test, a validated experimental paradigm for rodent-specific anxiety-like behavior. FTY720 treatment failed to ameliorate anxiety-like symptoms, irrespective of dosage. On the other hand, it was effective in reducing inflammatory infiltration, microglial reactivity and levels of pro-inflammatory molecules in the hippocampus, confirming the anti-inflammatory capacity of treatment. To explore the absence of FTY720 effect on behavior, we confirmed expression of S1P receptors (S1PR) S1PR1, S1PR3 and S1PR5 in the hippocampus and mapped the dynamics of these receptors in response to drug treatment alone, or in combination with EAE induction. We identified a complex pattern of responses, differing between (1) receptors, (2) dosage and (3) hippocampal sub-field. FTY720 treatment in the absence of EAE resulted in overall downregulation of S1PR1 and S1PR3, while S1PR5 exhibited a dose-dependent upregulation. EAE induction alone resulted in overall downregulation of all three receptors. On the other hand, combined FTY720 and EAE showed generally no effect on S1PR1 and S1PR3 expression except for the fimbrium region, but strong upregulation of S1PR5 over the range of doses examined. These data illustrate a hitherto undescribed complexity of S1PR response to FTY720 in the hippocampus, independent of drug effect on effector immune cells, but simultaneously emphasize the need to explore novel treatment strategies to specifically address mood disorders in MS.

scholarly journals Targeting Aging Pathways in Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6924
Author(s):  
Molly Easter ◽  
Seth Bollenbecker ◽  
Jarrod W. Barnes ◽  
Stefanie Krick
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Nutrient Sensing ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Telomere Attrition ◽  
Global Epidemic ◽  
Novel Treatment Strategies

Chronic obstructive pulmonary disease (COPD) has become a global epidemic and is the third leading cause of death worldwide. COPD is characterized by chronic airway inflammation, loss of alveolar-capillary units, and progressive decline in lung function. Major risk factors for COPD are cigarette smoking and aging. COPD-associated pathomechanisms include multiple aging pathways such as telomere attrition, epigenetic alterations, altered nutrient sensing, mitochondrial dysfunction, cell senescence, stem cell exhaustion and chronic inflammation. In this review, we will highlight the current literature that focuses on the role of age and aging-associated signaling pathways as well as their impact on current treatment strategies in the pathogenesis of COPD. Furthermore, we will discuss established and experimental COPD treatments including senolytic and anti-aging therapies and their potential use as novel treatment strategies in COPD.

Quantum, Brain, and Immunity Triangle in Mental Health and Neurosciences

2021 ◽  
Vol 19 (8) ◽  
pp. 131-140
Author(s):  
James Paul Pandarakalam
Keyword(s):  
Psychiatric Disorders ◽  
Psychotic Disorders ◽  
Treatment Strategies ◽  
Research Field ◽  
Psychotic Symptoms ◽  
Autoimmune Reaction ◽  
Neurotoxic Effects ◽  
Novel Treatment Strategies ◽  
The Brain ◽  
Immune Disturbance

Immunopsychiatry is a fledgling research field with great potential in the etiological research of psychotic disorders and can turn out to be helpful in finding novel treatment strategies and repurposing existing therapeutic agents. The clinical applications of Neuroquantology complement some of the etiological views of psychotic disorders that are evolving in immunopsychiatry. The pathogenesis of psychotic process may involve an underlying immune disturbance leading to neuro-quantological disorders. The cytokine storm that occurs due to COVID-19 and the resulting neurotoxic effects illustrate how an autoimmune reaction can potentially form psychotic symptoms through the mediation of the brain. Studying the interconnection between neurotransmission and immunity has significant relevance in the etiopathogenesis of psychiatric disorders. Immunopsychiatry alone may not be adequate to explain the development of psychotic symptoms, but Neuroquantology and immunopsychiatry complement each other in this endeavor. An expanded model of the brain–mind consciousness complex is required to understand the intricacies of psychotic symptomatology and contributions from Neuroquantology are highly enrichening. The claims of the practitioners of quantum immunotherapies need further exploration. Quantum-brain and immunity triangle can result in a huge paradigmatic shift in our understanding of psychiatric disorders and the evolving landscape of immunopsychiatry and clinical Neuroquantology warrant further promotion.

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