Unveiling the Therapeutic Potential of Herba Epimedii: Enhancing Bone Healing Through Cytoskeletal Regulation of RhoA/Rock1 Pathway.

Herba Epimedii is widely used to promote bone healing, and their active ingredients are total flavonoids of Epimedium (TFE). Ras homolog gene family member A / Rho-associated protein kinase (RhoA/Rock), an important pathway regulating the cytoskeleton, has been proven to affect bone formation. However, whether TFE promotes bone healing via this pathway remains unclear. In this study, the therapeutic effects of TFE were estimated using micro-computed tomography and hematoxylin and eosin staining of pathological sections. F-actin in osteoblasts was stained to investigate the protective effects of TFE on the cytoskeleton. Its regulatory effects on the RhoA/Rock1 pathway were explored using RT-qPCR and Western blot analysis. Besides, flow cytometry, alkaline phosphatase and nodule calcification staining were performed to evaluate the effects on osteogenesis. The bone healing in rats was improved, the cytoskeletal damage in osteoblasts was reduced, the RhoA/Rock1 pathway was downregulated, and osteogenesis was enhanced after TFE treatment. Thus, TFE can promote bone formation at least partially by regulating the expression of key genes and proteins in the cytoskeleton. The findings of this study provided evidence for clinical applications and would contribute to a better understanding of Epimedium's mechanisms in treating bone defects.

A regression method for EEG-based cross-dataset fatigue detection.

Introduction: Fatigue is dangerous for certain jobs requiring continuous concentration. When faced with new datasets, the existing fatigue detection model needs a large amount of electroencephalogram (EEG) data for training, which is resource-consuming and impractical. Although the cross-dataset fatigue detection model does not need to be retrained, no one has studied this problem previously. Therefore, this study will focus on the design of the cross-dataset fatigue detection model. Methods: This study proposes a regression method for EEG-based cross-dataset fatigue detection. This method is similar to self-supervised learning and can be divided into two steps: pre-training and the domain-specific adaptive step. To extract specific features for different datasets, a pretext task is proposed to distinguish data on different datasets in the pre-training step. Then, in the domain-specific adaptation stage, these specific features are projected into a shared subspace. Moreover, the maximum mean discrepancy (MMD) is exploited to continuously narrow the differences in the subspace so that an inherent connection can be built between datasets. In addition, the attention mechanism is introduced to extract continuous information on spatial features, and the gated recurrent unit (GRU) is used to capture time series information. Results: The accuracy and root mean square error (RMSE) achieved by the proposed method are 59.10% and 0.27, respectively, which significantly outperforms state-of-the-art domain adaptation methods. Discussion: In addition, this study discusses the effect of labeled samples. When the number of labeled samples is 10% of the total number, the accuracy of the proposed model can reach 66.21%. This study fills a vacancy in the field of fatigue detection. In addition, the EEG-based cross-dataset fatigue detection method can be used for reference by other EEG-based deep learning research practices.

Borneol-modified tanshinone IIA liposome improves cerebral ischemia reperfusion injury by suppressing NF-κB and ICAM-1 expression.

OBJECTIVE: To investigate the metabolism and brain tissue distribution of borneol-modified tanshinone IIA liposome (BO-TA-Lip) and its effect on NF-κB and ICAM-1 in cerebral ischemia reperfusion rats, thereby exploring the ameliorative mechanism of BO-TA-Lip on ischemic encephalopathy. METHODS: Particle size, entrapment efficiency, drug loading were measured to evaluate the preparation comprehensively. Metabolism and brain tissue distributions in vivo were measured by HPLC, and the pharmacokinetic parameters were calculated. In addition, 24 SD rats were randomly divided into sham, model, STS (sodium tanshinone IIA sulfonate, 30 mg/kg) and BO-TA-Lip groups (44 mg/kg). The middle cerebral artery occlusion (MCAO) rats were constructed with thread embolism method. Neurological deficits were scored using Zea Longa scoring standard. TTC and HE staining were used for the cerebral infarction and histopathological examination, respectively. The protein expression was examined by immunohistochemistry and Western blot. RESULTS: The average particle size, encapsulation efficiency and drug loading of BO-TA-Lip were (135.33 ± 7.25) nm, (85.95 ± 3.20)% and (4.06 ± 0.31)%, respectively. Both in the pharmacokinetic analysis of plasma and brain tissue, in BO-TA-Lip group, the peak concentration and the area under the curve increased, and the clearance rate decreased. The neurological deficit scores and infarct area of the BO-TA-Lip group were significantly lower than that of the model and STS groups. Besides, BO-TA-Lip reduced the protein expression of NF-κB, ICAM-1, IL-1ß, TNF-α and IL-6 in the brain tissue. CONCLUSION: BO-TA-Lip had higher bioavailability and better absorption in brain tissue, and could improve cerebral ischemia reperfusion injury, which might be related to the inhibitory effect of BO-TA-Lip in expression of NF-κB and ICAM-1.

Absorption and utilisation of epimedin C and icariin from Epimedii herba, and the regulatory mechanism via the BMP2/ Runx2 signalling pathway.

Bone nonunion remains a challenge during the treatment of bone defect accompanied with infection. Epimedii herba is a widely used medicine in clinic to enhance bone healing. Epimedin C and icariin are the major flavonoid glycosides from Epimedii herba. Although the effects of these compounds have been reported, their different absorption and utilisation by osteoblasts remain unclear. In the present study, lipopolysaccharide (LPS)-induced osteoblast was adopted as the model cell to evaluate the effects of epimedin C and icariin. The intracellular and extracellular drug concentrations within 24 h were assayed by pipette tip solid-phase extraction and high-performance liquid chromatography, respectively. MTT, alkaline phosphatase (ALP) and calcified nodule staining were performed to identify and evaluate the effects of epimedin C and icariin on LPS-induced osteoblasts. The regulatory roles of epimedin C and icariin in the bone morphogenetic protein-2 (BMP-2)/Runt-related transcription factor 2 (Runx2) signalling pathway were investigated. The results revealed that epimedin C and icariin were not efficiently absorbed by LPS-induced osteoblasts. Nevertheless, they still had high utilisation efficiency after entering the cells. ALP activity, mineralisation and osteoblasts proliferation were enhanced by a high concentration of epimedin C and icariin. The suppressed expression of BMP-2 and Runx2 in LPS-induced osteoblasts was up-regulated significantly after treatment with epimedin C and icariin. These findings firstly illustrated the behavior of epimedin C and icariin from Epimedii herba on LPS-induced osteoblasts and the regulatory property on the expression of key genes and proteins of the BMP-2/Runx2 signalling pathway, which might be helpful for better understanding flavonoids' mechanism to enhance bone repair and improving their future application.

[Clinical experience on treating Toxoplasma gondii infection during pregnancy by using acetyl spiramycin combined with azithromycin].

OBJECTIVE: To explore an effective therapy for pregnant Toxoplasma gondii infection by using acetyl spiramycin combined with azithromycin. METHODS: ELISA and PCR were used to diagnose and evaluate the therapy efficiency to toxoplasmosis in pregnant women. RESULTS: The serological test showed that the positive rates of specific antibodies IgM and IgG to Toxoplasma gondii in 285 pregnant women were 1.05% (3/285) and 5.97% (17/285), respectively. All the 3 cases of serum IgM positive pregnant women received the amniotic fluid PCR tests for Toxoplasma gondii DNA and 2 were positive, and they received spiramycin combined with azithromycin. After the therapy, their serum IgM antibody specific to Toxoplasma gondii and positive amniotic fluid PCR test for Toxoplasma gondii DNA turned to be negative. CONCLUSION: Acetyl spiramycin in combination with azithromycin is effective in the treatment of pregnant toxoplasmosis.