Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment
Discussion: These results highlight the broad scope of potential payloads and suitable conjugation chemistries paving the way for future SMDCs harnessing the safety features of targeted delivery approaches in combination with NE cleavage in the TME. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Source Type: research
A peptide derived from TID1S rescues frataxin deficiency and mitochondrial defects in FRDA cellular models
Friedreich’s ataxia (FRDA), the most common recessive inherited ataxia, results from homozygous guanine–adenine–adenine (GAA) repeat expansions in intron 1 of the FXN gene, which leads to the deficiency of frataxin, a mitochondrial protein essential for iron-sulphur cluster synthesis. The study of frataxin protein regulation might yield new approaches for FRDA treatment. Here, we report tumorous imaginal disc 1 (TID1), a mitochondrial J-protein cochaperone, as a binding partner of frataxin that negatively controls frataxin protein levels. TID1 interacts with frataxin both in vivo in mouse cortex and in vitro in corti...
Source: Frontiers in Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Source Type: research
JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target
Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear desp...
Source: Frontiers in Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Source Type: research
Chemico-pharmacological evaluation of the methanolic leaf extract of Catharanthus ovalis: GC –MS/MS, in vivo, in vitro, and in silico approaches
Conclusion: Further investigation needs to be conducted to specify and identify the exact mechanism of action of these compounds. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Source Type: research
Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells
As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of pat...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies
Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a–5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. O...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Orphan G protein-coupled receptors: the ongoing search for a home
G protein-coupled receptors (GPCRs) make up the largest receptor superfamily, accounting for 4% of protein-coding genes. Despite the prevalence of such transmembrane receptors, a significant number remain orphans, lacking identified endogenous ligands. Since their conception, the reverse pharmacology approach has been used to characterize such receptors. However, the multifaceted and nuanced nature of GPCR signaling poses a great challenge to their pharmacological elucidation. Considering their therapeutic relevance, the search for native orphan GPCR ligands continues. Despite limited structural input in terms of 3D crysta...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Novel insight into the therapeutical potential of flavonoids from traditional Chinese medicine against cerebral ischemia/reperfusion injury
Cerebral ischemia/reperfusion injury (CIRI) is a major contributor to poor prognosis of ischemic stroke. Flavonoids are a broad family of plant polyphenols which are abundant in traditional Chinese medicine (TCM) and have beneficial effects on several diseases including ischemic stroke. Accumulating studies have indicated that flavonoids derived from herbal TCM are effective in alleviating CIRI after ischemic stroke in vitro or in vivo, and exhibit favourable therapeutical potential. Herein, we systematically review the classification, metabolic absorption, neuroprotective efficacy, and mechanisms of TCM flavonoids against...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment
This study aims to provide an overview of the therapeutic potential of silibinin in the treatment and prevention of cancers. A comprehensive search was conducted using various internet databases such as PubMed, Google Scholar, and ScienceDirect to identify relevant research papers. Silibinin has been shown to exhibit anticancer activity against several types of cancers, including liver, lungs, breast, prostate, colorectal, skin, and bladder cancers. Its multifaceted mechanisms of action contribute to its therapeutic effects. Silibinin exerts antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Phenolic phytochemistry, in vitro, in silico, in vivo, and mechanistic anti-inflammatory and antioxidant evaluations of Habenaria digitata
In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening ...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Effect of age and ICU types on mortality in invasive mechanically ventilated patients with sepsis receiving dexmedetomidine: a retrospective cohort study with propensity score matching
Conclusion: Dexmedetomidine was associated with lower 28-day mortality in critically ill patients with sepsis receiving invasive mechanical ventilation, regardless of whether patients were younger or elderly, the first admission to the SICU or non-SICU. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Phyto-pharmacological evaluation and characterization of the methanolic extract of the Baccaurea motleyana M üll. Arg. seed: promising insights into its therapeutic uses
Conclusion: These findings lay the groundwork for future research, emphasizing the exploration of B. motleyana as a source of natural remedies for addressing prevalent health conditions. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Nobiletin from citrus peel: a promising therapeutic agent for liver disease-pharmacological characteristics, mechanisms, and potential applications
In conclusion, NOB may be a promising drug candidate for treating liver disease and can accelerate its application from the laboratory to the clinic. However, more high-quality clinical trials are required to validate its efficacy and identify its molecular mechanisms and targets. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
Commentary: A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
The combination of paeonol, diosmetin-7-O- β-D-glucopyranoside, and 5-hydroxymethylfurfural from Trichosanthis pericarpium alleviates arachidonic acid-induced thrombosis in a zebrafish model
Trichosanthis fruit (TF) is a classic medicinal material obtained from Shandong, China. The peel of this fruit (Trichosanthis pericarpium, TP) is known to exert anti-thrombotic effects. However, the anti-thrombotic active components and mechanisms of TP have yet to be fully elucidated. Combined with zebrafish models and high-performance liquid chromatography (HPLC), this study evaluated the endogenous anti-thrombotic effects with the combination of three compounds from TP. First, we used HPLC to investigate the components in the water extract of TP. Next, we used the zebrafish model to investigate the anti-thrombotic activ...
Source: Frontiers in Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research
