Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery

Stress-induced mental health disorders are affecting many people around the world. However, effective drug therapy for curing psychiatric diseases does not occur sufficiently. Many neurotransmitters, hormones, and mechanisms are essential in regulating the body's stress response. One of the most critical components of the stress response system is the hypothalamus-pituitary-adrenal (HPA) axis. The FKBP prolyl isomerase 51 (FKBP51) protein is one of the main negative regulators of the HPA axis. FKBP51 negatively regulates the cortisol effects (the end product of the HPA axis) by inhibiting the interaction between glucocorticoid receptors (GRs) and cortisol, causing reduced transcription of downstream cortisol molecules. By regulating cortisol effects, the FKBP51 protein can indirectly regulate the sensitivity of the HPA axis to stressors. Previous studies have indicated the influence of FKBP5 gene mutations and epigenetic changes in different psychiatric diseases and drug responses and recommended the FKBP51 protein as a drug target and a biomarker for psychological disorders. In this review, we attempted to discuss the effects of the FKBP5 gene, its mutations on different psychiatric diseases, and drugs affecting the FKBP5 gene

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection

<p>Abstract</p> <p>Background</p> <p>The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.</p> <p>Methods</p> <p>In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.</p> <p>Results</p> <p>Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.</p> <p>Conclusion</p> <p>These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.</p

The Current State of Proteomics in GI Oncology

Proteomics refers to the study of the entire set of proteins in a given cell or tissue. With the extensive development of protein separation, mass spectrometry, and bioinformatics technologies, clinical proteomics has shown its potential as a powerful approach for biomarker discovery, particularly in the area of oncology. More than 130 exploratory studies have defined candidate markers in serum, gastrointestinal (GI) fluids, or cancer tissue. In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years. We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy

The effects of transcranial direct-current stimulation (tDCS) on pain intensity of patients with fibromyalgia: a systematic review and meta-analysis

Abstract Introduction Fibromyalgia (FM) is a chronic pain condition that affects millions of people worldwide. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that has shown promise as a potential treatment for FM by modulating pain perception and reducing symptoms, such as fatigue and depression. We aimed to systematically review studies that assess the effect of tDCS on pain reduction in FM patients. Methods Seven electronic databases (PubMed, Scopus, Embase, PsycINFO, Web of Science, Cochrane, and CINAHL Complete) were searched for records in English. Studies that measured the effect of tDCS on pain intensity in FM patients were included. The Cochrane Collaboration’s tool was used to assess the quality of the included studies. A random-effect model was preferred, and statistical analysis was performed by Stata software version 17. Results Twenty studies were included for qualitative, and eleven for quantitative analysis. Out of 664 patients included in the study, 443 were in the stimulation group. The left M1 area was the most common stimulation target (n = 12), and 2 mA was the most common stimulation amplitude (n = 19). The analysis showed that active tDCS significantly reduced pain intensity in FM patients in comparison to the sham group (SMD= -1.55; 95% CI -2.10, -0.99); also, no publication bias was noted. Conclusion Our systematic review highlights the potential effect of tDCS on the reduction of pain intensity in FM patients. Additionally, this current evidence could suggest that tDCS applied at an intensity of 2mA to the left M1 is the most effective strategy

COVID‐19 as a trigger of Guillain‐Barré syndrome: A review of the molecular mechanism

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) caused a pandemic with serious complications. After coronavirus disease 2019 (COVID‐19), several post‐acute COVID‐19 syndromes (PACSs) and long‐COVID sequels were reported. PACSs involve many organs, including the nervous, gustatory, and immune systems. One of the PACSs after SARS‐CoV‐2 infection and vaccination is Guillain‐Barré syndrome (GBS). The incidence rate of GBS after SARS‐CoV‐2 infection or vaccination is low. However, the high prevalence of COVID‐19 and severe complications of GBS, for example, autonomic dysfunction and respiratory failure, highlight the importance of post‐COVID‐19 GBS. It is while patients with simultaneous COVID‐19 and GBS seem to have higher admission rates to the intensive care unit, and demyelination is more aggressive in post‐COVID‐19 GBS patients. SARS‐CoV‐2 can trigger GBS via several pathways like direct neurotropism and neurovirulence, microvascular dysfunction and oxidative stress, immune system disruption, molecular mimicry, and autoantibody production. Although there are few molecular studies on the molecular and cellular mechanisms of GBS occurrence after SARS‐CoV‐2 infection and vaccination, we aimed to discuss the possible pathomechanism of post‐COVID‐19 GBS by gathering the most recent molecular evidence

Lung Transplantation as a way to Escape Pneumonia in Patients with COVID-19: Lessons from ARDS and Influenza

In this era, the novel Coronavirus, referred to as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a life-threatening virus with a high mortality rate (4.2%) and with no absolute treatment as of yet, may ultimately result in acute respiratory distress syndrome (ARDS). ARDS is one of the fatal complications, highlighted by pulmonary infiltration and severe hypoxemia. This condition can be developed from primary lung inflammation caused by various viruses, particularly influenza viruses, some of the most common human pathogens. Due to this issue, many studies explored several approaches for ARDS treatment. Lung transplantation has been claimed as an efficient cure for severe ARDS and Influenza, which can also be offered for treating critical lung complications of SARS-CoV-2. Thereupon, to the best of our knowledge for the first time, we aimed to review all available data about capability of lung transplantation for the treatment of critically ill patients with ARDS, Influenza, and SARS-CoV-2