Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2020
Tetramethylpyrazine Induces Apoptosis and Inhibits Proliferation of Hypertrophic Scar-Derived Fibroblasts via Inhibiting the Phosphorylation of AKT.
Hypertrophic scar (HS) is a serious fibrotic skin disease and often considered as a kind of benign skin tumor. Tetramethylpyrazine (TMP), the main chemical composition of the traditional Chinese medicine Chuanxiong Rhizoma, has shown significant clinical benefits in the treatment of fibrosis disease and tumor, while the role in HS and the concrete mechanisms remain elusive. Herein, the protective effects of TMP in the treatment of HS was investigated and the results showed that the protein expression levels of type I collagen (Col I), type III collagen (Col III), and α-smooth muscle actin (α-SMA) were all inhibited remarkably after addition of TMP in HS-derived fibroblasts (HFs). ⋯ In addition, TMP treatment markedly reduced the phosphorylation levels of AKT. Taken together, our investigations demonstrated that TMP could down-regulate the expression of fibrosis-related molecules, inhibit scar fibroblast proliferation and activate cell apoptosis, during which AKT pathway was involved. Thus, this study shed more light on the pharmacological mechanisms of TMP, and provided a novel therapeutic alternative for prevention and treatment of HS.
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Frontiers in pharmacology · Jan 2020
Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention.
With the objective of linking early findings relating to the novel SARS-CoV-2 coronavirus with potentially informative findings from prior research literature and to promote investigation toward therapeutic response, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is consistent with a broad range of observed clinical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-λ-dependent epithelial defense. ⋯ Although certain elements are likely to be revised as new findings emerge, the proposed pathway suggests multiple points of investigation for potential therapeutic interventions. Initial candidate interventions include prophylaxis to augment epithelial defense (e.g., AT1 receptor blockade, type III and type I interferons, melatonin, calcitriol, camostat, and lopinavir) and to reduce viral load (e.g., remdesivir, ivermectin, emetine, Abelson kinase inhibitors, dopamine D2 antagonists, and selective estrogen receptor modulators). Additional interventions focus on tempering inflammatory signaling and injury (e.g., dexamethasone, doxycycline, Ang1-7, estradiol, alpha blockers, and DHA/EPA, pasireotide), as well as inhibitors targeted toward molecular mediators of the maladaptive COVID-19 immune response (e.g., IL-6, TNF-α, IL-17, JAK, and CDK9).
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Frontiers in pharmacology · Jan 2020
Comparative Efficacy of Chinese Herbal Injections for Pulmonary Heart Disease: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.
Given the severity of pulmonary heart disease and the wide utilization of Chinese herbal injections, this network meta-analysis was devised to assess the comparative efficacy of seven Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, and Shenqi Fuzheng injection) that were combined with Western medicines in the treatment of pulmonary heart disease. ⋯ In conclusion, Shenfu injection+ Western medicines, Shenmai injection+ Western medicines and Shenqi Fuzheng injection+ Western medicines may be potential optimal treatments for pulmonary heart disease. A larger sample size and high-quality randomized controlled trials are needed to confirm and support this network meta-analysis.
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Frontiers in pharmacology · Jan 2020
Intrathecal Oxytocin Improves Spontaneous Behavior and Reduces Mechanical Hypersensitivity in a Rat Model of Postoperative Pain.
The first few days post-surgery, patients experience intense pain, hypersensitivity and consequently tend to have minor locomotor activity to avoid pain. Certainly, injury to peripheral tissues produces pain and increases sensitivity to painful (hyperalgesia) and non-painful (allodynia) stimuli. In this regard, preemptive pharmacological treatments to avoid or diminish pain after surgery are relevant. ⋯ Hypersensitivity was evaluated using von Frey filaments, whereas spontaneous activity (total distance, vertical activity episodes, and time spent in the center of the box) was assessed in real time using a semiautomated open-field system. Under these conditions, we found that animals pretreated with spinal oxytocin before plantar incision showed a diminution of hypersensitivity and an improvement of spontaneous behavior (particularly total distance and vertical activity episodes). This report provides a basis for addressing the therapeutic relevance of oxytocin as a potential preemptive analgesic molecule.
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Frontiers in pharmacology · Jan 2020
ReviewAvailable Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19?
The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. ⋯ Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.