Introduction: Neuroinflammation is an important pathological event contributing to the onset and progression of neurodegenerative diseases. The hyperactivation of microglia triggers the release of excessive proinflammatory mediators that lead to the leaky blood-brain barrier and impaired neuronal survival. Andrographolide (AN), baicalein (BA) and 6-shogaol (6-SG) possess anti-neuroinflammatory properties through diverse mechanisms of action. The present study aims to investigate the effects of the pair-combinations of these bioactive compounds in attenuating neuroinflammation.Methods: A tri-culture model with microglial N11 cells, microvascular endothelial MVEC(B3) cells, and neuroblastoma N2A cells was established in a transwell system. AN, BA and 6-SG used alone (25 µM) or in pair-wised combinations (12.5 + 12.5 µM) were subjected to the tri-culture system. Upon the stimulation of lipopolysaccharides (LPS) at 1 μg/mL, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels were determined by ELISA assays. Immunofluorescence staining was applied to investigate the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) on N11 cells, expressions of protein zonula occludens-1 (ZO-1) on MVEC cells and phosphorylated tau (p-tau) on N2A cells, respectively. The endothelial barrier permeability of MVEC cells was assessed by the Evans blue dye, and the resistance from the endothelial barrier was measured by transepithelial/endothelial electrical resistance (TEER) value. Neuronal survival of N2A cells was determined by Alamar blue and MTT assays.Results: Combinations of AN-SG and BA-SG synergistically lowered the TNF and IL-6 levels in LPS-induced N11 cells. Remarkably, the combined anti-neuroinflammatory effects of AN-SG and BA-SG remained significantly greater compared to their individual components at the same concentration level. The molecular mechanism of the attenuated neuroinflammation was likely to be mediated by downregulation of NF-κB p65 translocation (p < 0.0001 vs. LPS stimulation) in N11 cells. In the MVEC cells, both AN-SG and BA-SG restored TEER values, ZO-1 expression and reduced permeability. Furthermore, AN-SG and BA-SG significantly improved neuronal survival and reduced expressions of p-tau on N2A cells.Discussion: The AN-SG and BA-SG combinations showed greater anti-neuroinflammatory potential than those used alone in mono- and tri-cultured N11 cells, thereby further protecting endothelial tight junction and neuronal survival. Taken together, AN-SG and BA-SG may provide improved anti-neuroinflammatory and neuroprotective activities.

Background: Cervical cancer (CC) is a major health threat to females, and distal metastasis is common in patients with advanced CC. Anoikis is necessary for the development of distal metastases. Understanding the mechanisms associated with anoikis in CC is essential to improve its survival rate.Methods: The expression matrix of long non-coding RNAs (lncRNAs) from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients was extracted from The Cancer Genome Atlas (TCGA), and highly relevant anoikis-related lncRNAs (ARLs) were identified by the single sample gene set enrichment analysis (ssGSEA) method. ARLs-related molecular subtypes were discerned based on prognosis-related ARLs. ARLs-related prognostic risk score (APR_Score) was calculated and risk model was constructed using LASSO COX and COX models. In addition, we also assessed immune cell activity in the immune microenvironment (TME) for both subtypes and APR_Score groups. A nomogram was utilized for predicting improved clinical outcome. Finally, this study also discussed the potential of ARLs-related signatures in predicting response to immunotherapy and small molecular drugs.Results: Three ARLs-related subtypes were identified from TCGA-CESC (AC1, AC2, and AC3), with AC3 patients having the highest ARG scores, higher angiogenesis scores, and the worst prognosis. AC3 had lower immune cell scores in TME but higher immune checkpoint gene expression and higher potential for immune escape. Next, we constructed a prognostic risk model consisting of 7-ARLs. The APR_Score exhibited a greater robustness as an independent prognostic indicator in predicting prognosis, and the nomogram was a valuable tool for survival prediction. ARLs-related signatures emerged as a potential novel indicator for immunotherapy and small molecular drug selection.Conclusion: We firstly constructed novel ARLs-related signatures capable of predicting prognosis and offered novel ideas for therapy response in CC patients.

To effectively respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an increasing number of researchers are focusing on the antiviral activity of cepharanthine (CEP), which is a clinically approved drug being used for over 70 years. This review aims to provide a brief overview of CEP and summarize its recent findings in quantitative analysis, pharmacokinetics, therapeutic potential, and mechanism in antiviral and anti-SARS-CoV-2 activity. Given its remarkable capacity against SARS-CoV-2 infection in vitro and in vivo, with its primary target organ being the lungs, and its good pharmacokinetic profile; mature and stable manufacturing technique; and its advantages of safety, effectiveness, and accessibility, CEP has become a promising drug candidate for treating COVID-19 despite being an old drug.

Introduction: Pulmonary fibrosis (PF) is a severe disease that can lead to respiratory failure and even death. However, currently there is no effective treatment available for patients with PF. Mesenchymal stem cells (MSCs) have been recently shown to have therapeutic potential for PF. We analyzed the literature focused of MSCs and PF to provide a comprehensive understanding of the relationship between MSCs and PF.Methods: We searched the Web of Science Core Collection database for literature from 2002 through 2021 that involved MSCs and PF. The included studies were then analyzed using CiteSpace and VOSviewers software.Results: A total of 1,457 studies were included for analysis. Our findings demonstrated the following: 1) an increasing trend of MSC and PF research; 2) among the 54 countries/regions of author affiliations, the United States was the most frequent, and the University of Michigan (n = 64, 2.8%) was the top institution; 3) Rojas Mauricio published the most articles and PLOS ONE had the most related studies; and 4) keywords, such as idiopathic pulmonary fibrosis, mesenchymal stem cells, and systemic sclerosis, were listed more than 100 times, indicating the research trend. Other common keywords, such as inflammation, myofibroblasts, fibroblasts, aging, telomerase or telomere, and extracellular matrix demonstrate research interests in the corresponding mechanisms.1) The number of publications focused on MSCs and PF research increased during the study period; 2) Among the 54 countries/regions of author affiliations, most articles were published in the United States of America, and the University of Michigan (n = 64, 2.8%) had the largest number of publications; 3) Rojas Mauricio published the most articles and PLOS ONE had the most related studies; 4) Keywords, such as idiopathic pulmonary fibrosis, MSCs, and systemic sclerosis, were listed more than 100 times, representing a research trend. Other common keywords included inflammation, myofibroblasts, fibroblasts, aging, telomerase or telomere, and extracellular matrix.Discussion: During the past 2 decades, MSCs have been proposed to play an important role in PF treatment. An increasing amount of literature focused on MSCs and PF research has been published. Our findings provide insight into the current status and research trends in the field of MSCs and PF research during the past 2 decades, which could help researchers understand necessary research directions. In the future, more preclinical and clinical studies should be conducted in this field to support the application of MSCs in the treatment of PF.

Taxifolin is a flavonoid compound, originally isolated from the bark of Douglas fir trees, which is often found in foods such as onions and olive oil, and is also used in commercial preparations, and has attracted the interest of nutritionists and medicinal chemists due to its broad range of health-promoting effects. It is a powerful antioxidant with excellent antioxidant, anti-inflammatory, anti-microbial and other pharmacological activities. This review focuses on the breakthroughs in taxifolin for the treatment of diseases from 2019 to 2022 according to various systems of the human body, such as the nervous system, immune system, and digestive system, and on the basis of this review, we summarize the problems of current research and try to suggest solutions and future research directions.

Asarum essential oil (AEO) has been shown to have good pharmacological activities for the anti-inflammatory and analgesic effects, but increasing the dose may cause toxicity. Therefore, we studied the toxic and pharmacodynamic components of AEO by molecular distillation (MD). Anti-inflammatory activity was assessed using RAW264.7 cells. Neurotoxicity was assessed in PC12 cells and the overall toxicity of AEO was evaluated in the mouse acute toxicity assay. The results showed that AEO is primarily composed of safrole, methyl eugenol, and 3,5-dimethoxytoluene. After MD, three fractions were obtained and contained different proportions of volatile compounds relative to the original oil. The heavy fraction had high concentrations of safrole and methyl eugenol, while the light fraction contained high concentrations of α-pinene and β- pinene. The original oil and all three fractions exhibited anti-inflammatory effects, but the light fraction demonstrated more excellent anti-inflammatory activity than the other fractions. Asarum virgin oil and MD products are all neurotoxic. The exposure of PC12 cells to high concentrations of AEO resulted in abnormal nuclei, an increased number of apoptotic cells, increased ROS formation, and decreased SOD levels. Moreover, the results of acute toxicity tests in mice revealed that the light fractions were less toxic than virgin oils and other fractions. In summary, the data suggest that the MD technology enables the enrichment and separation of essential oil components and contributes to the selection of safe concentrations of AEO.