Frontiers in Pharmacology

The serotonin hypothesis of depression is still influential, but the relationship between peripheral 5-HT levels and depression is still unknown. This review aimed to verify whether peripheral 5-HT levels could be used as a biomarker for depression diagnosis and treatment. PubMed and EMBASE were searched using terms appropriate to the area of research. Articles from 1957 to 2022 in the following terms were identified: depression, 5-HT, serotonin and peripheral (serum, plasma, blood platelets). 33 studies were included: seven clinical trials about periphery 5-HT levels in depressive patients compared to normal subjects, 15 clinical trials about changes of peripheral 5-HT levels in patients with depression after drug treatment and 11 animal experiments about peripheral 5-HT levels in animal models of depression...

Ovarian cancer (OC) remains the most fatal disease of gynecologic malignant tumors. Angiogenesis refers to the development of new vessels from pre-existing ones, which is responsible for supplying nutrients and removing metabolic waste. Although not yet completely understood, tumor vascularization is orchestrated by multiple secreted factors and signaling pathways. The most central proangiogenic signal, vascular endothelial growth factor (VEGF)/VEGFR signaling, is also the primary target of initial clinical anti-angiogenic effort...

Background: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) therapy may experience further damage to the vascular endothelium, leading to increased inflammatory response and in-stent thrombosis. In many clinical studies, sodium tanshinone IIA sulfonate injection (STS) has been found to reduce inflammatory factors and enhance vascular endothelial function in patients with ACS while improving the prognosis of PCI. However, to date, there has been no systematic review assessing the effectiveness and safety of STS on inflammatory factors and vascular endothelial function...

Renal fibrosis is a common pathological outcome of various chronic kidney diseases, and as yet, there is no specific treatment. Dapagliflozin has shown renal protection in some clinical trials as a glucose-lowering drug, but its role and mechanism on renal fibrosis remain unclear. In this study, we used a 0.2% adenine diet-induced renal fibrosis mouse model to investigate whether dapagliflozin could protect renal function and alleviate renal fibrosis in this animal model. In vivo , we found that dapagliflozin's protective effect on renal fibrosis was associated with 1) sustaining mitochondrial integrity and respiratory chain complex expression, maintained the amount of mitochondria; 2) improving fatty acid oxidation level with increased expression of CPT1-α, PPAR-α, ACOX1, and ACOX2; 3) reducing inflammation and oxidative stress, likely via regulation of IL-1β, IL-6, TNF-α, MCP-1, cxcl-1 expression, and glutathione (GSH) activity, superoxide dismutase (SOD) and malondialdehyde (MDA) levels; and 4) inhibiting the activation of the TGF-β1/MAPK pathway...

Obesity is one of the most prevalent chronic metabolic diseases, and induction of apoptosis in preadipocytes and adipocytes is a potential strategy to treat obesity. Celastrol represents one of the most robust anti-obesity phytochemicals so far, yet its direct binding target remains elusive. Here, we determined that celastrol could induce apoptosis in preadipocytes via mitochondrial mediated pathway. Further study clarified that celastrol inhibited the fusion of autophagosome and lysosome to prohibit autophagy, leading to cell apoptosis...

Glioblastoma multiforme (GBM) is a brain tumor with high mortality and recurrence rate. Radiotherapy and chemotherapy after surgery are the main treatment options available for GBM. However, patients with glioblastoma have a grave prognosis. The major reason is that most GBM patients are resistant to radiotherapy. UBA1 is considered an attractive potential anti-tumor therapeutic target and a key regulator of DNA double-strand break repair and genome replication in human cells. Therefore, we hypothesized that TAK-243, the first-in-class UBA1 inhibitor, might increase GBM sensitivity to radiation...

A series of novel ferulic acid derivatives were designed and synthesized, and the twenty-one compounds were evaluated for their antiviral activities against Respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), and enterovirus type 71 (EV71). These derivatives with the core structure of diphenyl acrylic acids had cis-trans isomers, which were confirmed by 1 H NMR, HPLC, and UV-vis spectra for the first time. The A5 had a selective effect against RSV but no work on herpes simplex virus type 1 and enterovirus type 71, which showed a therapeutic index (TI) of 32 and was significantly better than ferulic acid...

Objective: Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer's disease (AD). Methods: A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition...

Medicines from natural products can not only treat neurodegenerative diseases but also improve the cognitive dysfunction caused by treatments with western medicines. This study reviews the literature related to the regulation of mitochondrial participation in cognitive function by natural products. In this study, we focused on English articles in PubMed, Web of Science, and Google Scholar, from 15 October 2017, to 15 October 2022. Fourteen studies that followed the inclusion criteria were integrated, analyzed, and summarized...

[This corrects the article DOI: 10.3389/fphar.2022.1045102.].

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic strategies of multiple types of malignancies including lymphoma. However, efficiency of ICIs varies dramatically among different lymphoma subtypes, and durable response can only be achieved in a minority of patients, thus requiring unveiling the underlying mechanisms of ICI resistance to optimize the individualized regimens and improve the treatment outcomes. Recently, accumulating evidence has identified potential prognostic factors for ICI therapy, including tumor mutation burden and tumor microenvironment (TME)...

Introduction : Epidemiological studies in children suggested that in utero exposure to chlorpyrifos (CPF), an organophosphate insecticide, may cause developmental neurotoxicity (DNT). We applied quantitative in vitro - in vivo extrapolation (QIVIVE) based on in vitro concentration and non-choline esterase-dependent effects data combined with Benchmark dose (BMD) modelling to predict oral maternal CPF exposure during pregnancy leading to fetal brain effect concentration. By comparing the results with data from epidemiological studies, we evaluated the contribution of the in vitro endpoints to the mode of action (MoA) for CPF-induced DNT...

No abstract text is available yet for this article.

Receptor-interacting serine/threonine kinase 2 (RIPK2) is a vital immunomodulator that plays critical roles in nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs) signaling. Stimulated NOD1 and NOD2 interact with RIPK2 and lead to the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK), followed by the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23. Defects in NOD/RIPK2 signaling are associated with numerous inflammatory diseases, including asthma, sarcoidosis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), multiple sclerosis, and Blau syndrome...

Objective: Chronic kidney disease (CKD) has significant effects on renal clearance of drugs. The application of antibiotics in CKD patients to achieve the desired therapeutic effect is challenging. This study aims to determine meropenem plasma exposure in the CKD population and further investigate optimal dosing regimens. Methods: A healthy adult PBPK model was established using the meropenem's physicochemical parameters, pharmacokinetic parameters, and available clinical data, and it was scaled to the populations with CKD and dialysis...

Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from in vivo towards the use of alternative in vitro human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung...

Behçet disease (BD) is a chronic systemic vasculitis that is clinically characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin lesions. Here, we conducted bulk RNA-seq of skin samples from 4 BD patients and 4 normal controls (NCs). A total of 260 differentially expressed genes (DEGs), including 99 upregulated and 161 downregulated genes, were detected in the skin lesions of BD patients compared to NCs. These DEGs were mainly enriched in the following biological processes: the activation and migration of immune cells, the release of proinflammatory factors, and the IFN-γ signaling pathway...

Background: The genetic factors in assessing therapeutic efficacy and predicting antihypertensive drug response are unclear. Therefore, this study aims to identify the associations between variants and antihypertensive drug response. Methods: A longitudinal study including 1837 hypertensive patients was conducted in Northern China and followed up for a median 2.24 years. The associations of 11 candidate variants with blood pressure changes in response to antihypertensive drugs and with the risk of cardiovascular events during the follow-up were examined...

The pathophysiology of Alzheimer's disease (AD) is multifactorial with characteristic extracellular accumulation of amyloid-beta (Aβ) and intraneuronal aggregation of hyperphosphorylated tau in the brain. Development of disease-modifying treatment for AD has been challenging. Recent studies suggest that deleterious alterations in neurovascular cells happens in parallel with Aβ accumulation, inducing tau pathology and necroptosis. Therefore, therapies targeting cellular Aβ and tau pathologies may provide a more effective strategy of disease intervention...

Niclosamide and benzbromarone have been described as inhibitors of the calcium activated chloride channel, TMEM16A, and on this basis have been considered and tested as clinical candidates for the treatment of airway diseases. However, both compounds have previously demonstrated activity on a range of additional biological targets and it is unclear from the literature to what extent any activity on TMEM16A may contribute to efficacy in these models of airway disease. The aim of the present study was therefore to examine the pharmacology and selectivity of these clinical candidates together with a structurally unrelated TMEM16A blocker, Ani9, in a range of functional assays to better appreciate the putative role of TMEM16A in the regulation of both epithelial ion transport and the development of an airway epithelial mucus secretory phenoptype...