Objective  In March 2022, more than 600 million cases of Corona Virus Disease 2019 (COVID-19) and about 6 million deaths have been reported worldwide. Unfortunately, while effective antiviral therapy has not yet been available, chloroquine (CQ)/hydroxychloroquine (HCQ) has been considered an option for the treatment of COVID-19. While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients' lives, controversial results have also been reported. One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval (LQT), an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias. Yet, the mechanisms for this cardiotoxicity of HCQ remained incompletely understood.  Materials and methods  Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes. HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene (hERG) K⁺ channels were used for whole-cell patch-clamp recordings of hERG K⁺ channel current (I_hERG). Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels, respectively.  Results  electrocardiogram (ECG) recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits. Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state. HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90 (Hsp90)/hERG complex. Moreover, the expression levels of connexin 43 (CX43) and Kir2.1, the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias, were decreased by HCQ, while those of Cav1.2, the main Ca²⁺ handling proteins, remained unchanged and SERCA2a was increased.  Conclusion  HCQ could induce LQT but did not induce arrhythmias, and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future.

  Background  Taxus cuspidata S. et Z. is a precious species of frigid zone plant belonging to the Taxaceae family, which possesses anticancer, anti-inflammatory, hypoglycemic, and antibacterial pharmacological properties. While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities, whether Taxus cuspidata S. et Z. has skin-protective actions against injuries remained unknown. This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition, oxidation, inflammation, and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage.  Methods  Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis method. Antioxidant capacity was evaluated by measuring superoxide dismutase (SOD) concentration and glutathione (GSH) content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay kit. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4 (GPX4). Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in mice. In a mouse model of skin allergy induced by 4-aminopyridine (4-AP), allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay (ELISA) kits. Two proinflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by qRT-PCR. Hematoxylin and eosin (HE) staining was conducted to assess the degree of skin lesion.  Results  All three Taxus extracts including Taxus chinensis essential oil, Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals, of which Taxus chinensis essential oil produced the greatest effect. In contrast, the three Taxus extracts elevated SOD and GSH levels in the skin tissues, and the highest increase was seen with Taxus chinensis essential oil. Three Taxus extracts, especially Taxus chinensis essential oil, effectively reduce the rate of ear and paw swelling. All three Taxus extracts reduced the number of body licks, the levels of TNF-α and IL-1β, and the histamine content in tissue homogenates of mice and alleviated skin damage. Consistently, Taxus chinensis essential oil yielded the greatest magnitude of decreases.  Conclusion  While all three Taxus extracts possessed the anti-skin melanin deposition, oxidation, and allergy properties, Taxus chinensis essential oil produced the superior effects.

Hypertension is the most common cardiovascular condition in clinical practice and a major risk factor for stroke and cardiovascular events. There are more than 270 million hypertension patients in China, and the prevalence of hypertension in the high-latitude cold areas is significantly higher than in the low-latitude warm areas. The unique epidemiological characteristics and risk factors of hypertension in the cold regions of China urge for establishment of the prevention and control system for targeted and more effective management of the condition.

  Background  Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by a progressive decline in liver function, leading to disruptions in liver integrity and metabolic function, resulting in lipid deposition and excessive accumulation of extracellular matrix (ECM). The pathogenesis of NAFLD is complex and not yet fully understood, contributing to the absence of specific therapeutic strategies. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor pivotal in regulating lipid and glucose metabolism. However, the impacts of PPARγ on NAFLD remains insufficiently explored. Thus, this study aimed to investigate the role of PPARγ in NAFLD and its underlying molecular mechanisms.  Methods  Chemical detection kits were utilized to quantify collagen content, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) level variations. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells, while western blotting was conducted to analyze the levels of both PPARγ and the TGF-β/Smad signaling pathway.  Results  Our findings unveiled significantly reduced PPARγ expression in a rat model of NAFLD, leading to subsequent activation of the TGF-β/Smad signaling pathway. Furthermore, PPARγ activation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen production. On a cellular level, PPARγ activation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9), along with inflammatory response genes interleukin (IL)-1β and IL-6. Additionally, PPARγ activation led to a significant decrease in the levels of ALT and AST. At the molecular level, PPARγ notably down-regulated the TGF-β/Smad signaling pathway, which is known to promote liver fibrosis.  Conclusion  These groundbreaking findings underscore PPARγ activation as a promising therapeutic approach to delay NAFLD progression by targeting the TGF-β/Smad signaling pathway in hepatic cells. This highlights the potential of PPARγ as a promising therapeutic target for NAFLD management in clinical settings.

Thrombotic diseases are the leading causes of death worldwide, especially in cold climates. Traditional Chinese medicine (TCM)-based therapies have gained increasing popularity worldwide, but also raised some concerns about its efficacy, safety profile and exact mechanisms. TCM has been traditionally used in the management of thrombosis and convincingly proven effective in modifying thrombosis progression, particularly the platelet function, coagulation system and fibrinolytic system. This review article focuses on TCM regulation of thrombosis with brief discussion on the fundamental aspects and relevant background information for better understanding of the subject. In addition to its antithrombotic effects, we will dive insight into the cellular and molecular mechanisms of TCM as pharmacological regulators of platelet aggregation, coagulation, and fibrinolysis. With increasing awareness and understanding of the benefits and potentials of TCM, TCM products will in no doubt gain its broader applications in the treatment of thrombosis and associated disorders, which in turn will deepen our understanding of its pharmacological and molecular mechanisms. Finally, current review provides a perspective view on the future directions to TCM research on thrombosis.