Botulinum toxin A attenuates osteoarthritis development via inhibiting chondrocyte ferroptosis through SLC7Al1/GPX4 axis.

Osteoarthritis (OA) is a prevalent joint degenerative disease, resulting in a significant societal burden. However, there is currently a lack of effective treatment option available. Previous studies have suggested that Botulinum toxin A (BONT/A), a macromolecular protein extracted from Clostridium Botulinum, may improve the pain and joint function in OA patients, but the mechanism remains elusive. This study was to investigate the impact and potential mechanism of BONT/A on OA in vivo and in vitro experiment. LPS increased the levels of ROS, Fe2+and Fe3+, as well as decreased GSH levels, the ratio of GSH / GSSH and mitochondrial membrane potential. It also enhanced the degeneration of extracellular matrix (ECM) and altered the ferroptosis-related protein expression in chondrocytes. BONT/A rescued LPS-induced decrease in collagen type II (Collagen II) expression and increase in matrix metalloproteinase 13 (MMP13), mitigated LPS-induced cytotoxicity in chondrocytes, abolished the accumulation of ROS and iron, upregulated GSH and the ratio of GSH/ GSSH, improved mitochondrial function, and promoted SLC7A11/GPX4 anti-ferroptosis system activation. Additionally, intra-articular injection of BONT/A inhibited the degradation of cartilage in OA model rats. This chondroprotective effect of BONT/A was reversed by erastin (a classical ferroptosis agonist) and enhanced by liproxstatin-1 (a classic ferroptosis inhibitor). Our research confirms that BONT/A alleviates the OA development by inhibiting the ferroptosis of chondrocytes, which revealed to be a potential therapeutic mechanism for BONT/A treating the OA.

H89 dihydrochloride hydrate and calphostin C lower the body temperature through TRPV1.

The transient receptor potential vanilloid (TRPV1) serves as a negative regulator of body temperature, and during fever conditions its expression can lead to a decrease in temperature. TRPV1 is regulated by a variety of enzymes; however, it is currently unclear whether the regulation of TRPV1 phosphorylation may serve a role in the increase in TRPV1 expression during fever. In the present study, using an in vivo experimental method, rat brain ventricles were injected with the protein kinase A (PKA) antagonist, H89, and the protein kinase C (PKC) antagonist, calphostin C, and fever was induced using lipopolysaccharide (LPS) in order to detect the expression of TRPV1 and phosphorylated (p­)TRPV1, the intracellular Ca2+ concentration [(Ca2+)i] of hypothalami and rat body temperature. The results demonstrated that following the generation of fever using LPS, the expressions of TRPV1 and p­TRPV1, and hypothalamic [Ca2+]i markedly increased. In addition, following an injection with the PKA or PKC antagonist, the temperature increased further due to the inhibition of p­TRPV1. Thus, it was hypothesized that PKA and PKC may be involved in TRPV1 phosphorylation, resulting in a temperature reduction during LPS­induced fever conditions.

[Estimation of desert vegetation coverage based on multi-source remote sensing data].

Taking the lower reaches of Tarim River in Xinjiang of Northwest China as study areaAbstract: Taking the lower reaches of Tarim River in Xinjiang of Northwest China as study area and based on the ground investigation and the multi-source remote sensing data of different resolutions, the estimation models for desert vegetation coverage were built, with the precisions of different estimation methods and models compared. The results showed that with the increasing spatial resolution of remote sensing data, the precisions of the estimation models increased. The estimation precision of the models based on the high, middle-high, and middle-low resolution remote sensing data was 89.5%, 87.0%, and 84.56%, respectively, and the precisions of the remote sensing models were higher than that of vegetation index method. This study revealed the change patterns of the estimation precision of desert vegetation coverage based on different spatial resolution remote sensing data, and realized the quantitative conversion of the parameters and scales among the high, middle, and low spatial resolution remote sensing data of desert vegetation coverage, which would provide direct evidence for establishing and implementing comprehensive remote sensing monitoring scheme for the ecological restoration in the study area.

[Clinical observation of heparin-induced thrombocytopenia].

OBJECTIVE: To explore the treatment of heparin-induced thrombocytopenia (HIT) in venous thromboembolism. METHODS: A total of 202 patients with venous thromboembolism without anticoagulation contraindications were enrolled. All of them were treated with low molecular weight heparin (LMWH) and/or unfractionated heparin (UFH). The peripheral blood cells were examined regularly. RESULTS: HIT occurred in 6 patients. And argatroban was used to treat HIT. The overall incidence rate of HIT in this study was 2.97%. The time of occurrence of HIT was about Days 3 - 9 after using heparin. The platelet recovered to the basic level at Days 3 - 7 after withdrawing heparin and initiating argatroban. CONCLUSION: The count of platelet should be measured in the patients receiving regular LMWH and/or UFH therapy. And the above regimen should be discontinued timely when the platelet count declined progressively by over 50%. Argatroban was effective.

A missense mutation (G604S) in the S5/pore region of HERG causes long QT syndrome in a Chinese family with a high incidence of sudden unexpected death.

Long QT syndrome (LQTS) is characterized by abnormalities in cardiac repolarization that lead to prolongation of the electrocardiographic (ECG) QT interval. Mutations in the human ether-a-go-go-related gene (HERG, KCNH2) cause the chromosome 7-linked LQT2 form of congenital LQTS, which is characterized by a prolonged QT interval and a bifid T-wave with an increased susceptibility to life-threatening cardiac arrhythmias, especially in children. We describe the genotypic and phenotypic pedigree of a large Chinese family (n = 36) in which 11 members were diagnosed with LQTS on the basis of typical ECG patterns for LQT2. Symptomatic syncopal episodes appeared in seven members of this family at a young age; an additional four members had died suddenly at ages of 18, 19, 24 and 70 years, respectively. Screening for SCN5A and HERG candidate genes identified a heterozygous missense mutation 1810G-->A in exon 7 of HERG that leads to the substitution of the amino acid glycine by serine (G604S); this mutation was located in the S5/pore region of the HERG protein and was associated with a malignant phenotype. Ten of the family members carrying the mutation showed a prolongation of the corrected QT interval (QTc), and seven of these had experienced multiple syncopal episodes. The retrospective examination of documented ECG records revealed that one family member who had died suddenly also had a prolonged QT interval. This study is the first to demonstrate a close correlation between clinical phenotype and genotype with a 100% penetrance based on the pedigree of a Chinese family with LQT2.