Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis.

Introduction: Ephedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA. Methods: A type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman's correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites. Results: ESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-ß and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice. Conclusion: ESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects.

Icariin Regulates EMT and Stem Cell-Like Character in Breast Cancer through Modulating lncRNA NEAT1/TGFß/SMAD2 Signaling Pathway.

Metastases and drug resistance are the major risk factors associated with breast cancer (BC), which is the most common type of tumor affecting females. Icariin (ICA) is a traditional Chinese medicine compound that possesses significant anticancer properties. Long non-coding RNAs (lncRNAs) are involved in a wide variety of biological and pathological processes and have been shown to modulate the effectiveness of certain drugs in cancer. The purpose of this study was to examine the potential effect of ICA on epithelial mesenchymal transition (EMT) and stemness articulation in BC cells, as well as the possible relationship between its inhibitory action on EMT and stemness with the NEAT1/transforming growth factor ß (TGFß)/SMAD2 pathway. The effect of ICA on the proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony assays), EMT (Western blotting, immunofluorescence, and wound healing), and stemness (mammosphere formation assays, Western blotting) of BC cells were examined. According to the findings, ICA suppressed the proliferation, EMT, and stem cell-like in MDA-MB-231 cells, and exerted its inhibitory impact by downregulating the TGFß/SMAD2 signaling pathway. ICA could significantly downregulate the expression of lncRNA NEAT1, and silencing NEAT1 enhanced the effect of ICA in suppressing EMT and expression of different stem cell markers. In addition, silencing NEAT1 was found to attenuate the TGFß/SMAD2 signaling pathway, thereby improving the inhibitory impact of ICA on stemness and EMT in BC cells. In conclusion, ICA can potentially inhibit the metastasis of BC via affecting the NEAT1/TGFß/SMAD2 pathway, which provides a theoretical foundation for understanding the mechanisms involved in potential application of ICA for BC therapy.

Efficacy and safety of ciprofol (HSK3486) for procedural sedation and anesthesia induction in surgical patients: A systematic review and meta-analysis.

Background: Ciprofol (HSK3486) is a novel gamma-aminobutyric acid type A (GABAA) receptor agonist that has attracted wide attention because of its lower injection pain and fewer adverse events. We summarized all available evidence and analyzed the efficacy and safety of ciprofol during procedural sedation and anesthesia induction. Methods: An electronic search of PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, Science Direct, the Chinese National Knowledge Infrastructure, Wan Fang Data, and the VIP Chinese Journal Service platform was conducted from inception of databases to March 1, 2023. Risk ratio (RR) and mean difference (MD) with 95 % confidence interval (CI) were used separately for binary categorical and continuous variables. We performed trial sequential analysis and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to judge the certainty of evidence. Results: Fifteen randomized controlled trials with 2441 patients were included in this study. Ciprofol showed similar advantages to propofol in terms of induction success rate (RR = 1, 95 % CI = 0.99, 1.01, moderate certainty) and induction time (MD = 3.31, 95 % CI = -0.34, 6.95, low certainty), but did not increase the incidence of adverse events (RR = 0.88, 95 % CI = 0.78, 1.00, very low certainty), such as bradycardia (RR = 0.96, 95 % CI = 0.77, 1.21, high certainty), hypoxia (RR = 0.79, 95 % CI = 0.46, 1.37, p = 0.40, moderate certainty) and other adverse events. Although it may be associated with a longer time to be fully alert (MD = 1.22, 95 % CI = 0.32, 2.12, very low certainty), ciprofol significantly reduced injection pain (RR = 0.15, 95 % CI 0.09, 0.24, low certainty) and may have reduced the incidence of hypotension (RR = 0.77, 95 % CI = 0.63, 0.94, low certainty) and respiratory depression (RR = 0.29, 95 % CI = 0.15, 0.56, moderate certainty). Conclusion: Ciprofol and propofol had similar effects on most outcomes. While the time to full alertness may be prolonged, injection pain was significantly reduced, and hypotension and respiratory depression may be reduced compared with propofol. We believe that ciprofol is an effective alternative to intravenous anesthetic agents.

A comparation of dexmedetomidine and midazolam for sedation in patients with mechanical ventilation in ICU: A systematic review and meta-analysis.

BACKGROUND: The use of dexmedetomidine rather than midazolam may improve ICU outcomes. We summarized the available recent evidence to further verify this conclusion. METHODS: An electronic search of PubMed, Medline, Embase, Cochrane Library, and Web of Science was conducted. Risk ratios (RR) were used for binary categorical variables, and for continuous variables, weighted mean differences (WMD) were calculated, the effect sizes are expressed as 95% confidence intervals (CI), and trial sequential analysis was performed. RESULTS: 16 randomized controlled trials were enrolled 2035 patients in the study. Dexmedetomidine as opposed to midazolam achieved a shorter length of stay in ICU (MD = -2.25, 95%CI = -2.94, -1.57, p<0.0001), lower risk of delirium (RR = 0.63, 95%CI = 0.50, 0.81, p = 0.0002), and shorter duration of mechanical ventilation (MD = -0.83, 95%CI = -1.24, -0.43, p<0.0001). The association between dexmedetomidine and bradycardia was also found to be significant (RR 2.21, 95%CI 1.31, 3.73, p = 0.003). We found no difference in hypotension (RR = 1.44, 95%CI = 0.87, 2.38, P = 0.16), mortality (RR = 1.02, 95%CI = 0.83, 1.25, P = 0.87), neither in terms of adverse effects requiring intervention, hospital length of stay, or sedation effects. CONCLUSIONS: Combined with recent evidence, compared with midazolam, dexmedetomidine decreased the risk of delirium, mechanical ventilation, length of stay in the ICU, as well as reduced patient costs. But dexmedetomidine could not reduce mortality and increased the risk of bradycardia.

Effect of comprehensive nursing intervention for congenital heart disease in children: A meta-analysis.

OBJECTIVES: This meta-analysis aimed to assess the impact of nursing interventions (e.g., educational and empathic interviewing, motor exercise, therapeutic play interventions) on the perioperative outcome of children with congenital heart disease (CHD). METHODS: We searched PubMed, Embase, Web of Science, Scopus, Cochrane, EBSCO, The Chinese National Knowledge Infrastructure, Wan Fang Data and the VIP Chinese Journal Service platform from the date of database creation to August 2021. Our study adhered to the recommendations of the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RevMan 5.4 and Stata 16.0 were used to complete the meta-analysis. RESULTS: This meta-analysis showed that comprehensive nursing intervention reduced both the length of hospital stay (weighted mean difference [WMD] = -1.982, 95%CI [-2.329, -1.634], P < .001) and the related risk of post-operative complications [OR = 0.345, 95%CI (0.225, 0.528), P < .001]. In addition, nursing intervention increased parental satisfaction with the care provided [OR = 0.308, 95%CI (1.923, 6.863), P < .001]. Nursing interventions have also had a positive impact in reducing preoperative anxiety [WMD = -6.721, 95% CI (-7.194, -6.249), P < .001] and postoperative pain [WMD = -7.103, 95% CI (-7.103, -7.663), P < .001] in children. CONCLUSIONS: This meta-analysis confirms the beneficial effects of comprehensive nursing interventions in terms of reduced complication rates and shorter hospital stays. The effectiveness of comprehensive nursing in reducing anxiety and pain levels was also demonstrated. The findings support the implementation of comprehensive care interventions in the perioperative period for children with CHD to improve clinical outcomes.

pH-responsive Sulfated Hyaluronic Acid Nanoparticles Targeting Tumor Cells and CAFs for the Treatment of Breast Cancer.

BACKGROUND: Tumor metastasis is a main cause of death in patients with breast cancer. The cross-talk between cancer-associated fibroblasts (CAFs) and tumor cells plays an important role in promoting tumor invasion and metastasis. It is important to develop a novel delivery system to inhibit tumor development by simultaneously targeting both CAFs and tumor cells. OBJECTIVES: The main objective of this research was to prepare nanoparticles to inhibit tumor proliferation and migration by blocking the cross-talk of tumor-CAFs. Additionally, a novel "MCF- 7+NIH/3T3" mixed cell model was established to mimic the tumor microenvironment (TME). METHODS: In this study, the pH-responsive nanoparticles (MIF/DOX-sul-HA NPs) based on sulfated hyaluronic acid (sul-HA) polymers were prepared for co-delivery of doxorubicin (DOX) and mifepristone (MIF). The effects of anti-proliferation and anti-metastasis of MIF/DOX-sul-HA NPs were investigated both in vitro and in vivo. RESULTS: The results showed that MIF/DOX-sul-HA NPs were nearly spherical in shape with narrow particle size distribution and pH-responsive drug release, and could be taken up by both MCF-7 and NIH/3T3 cells. Compared with MCF-7 cells alone, the anti-tumor effect of single DOX was weak in the "MCF-7+NIH/3T3" mixed cell model. MIF/DOX-sul-HA NPs exhibited strong effects of anti-proliferation and anti-metastasis than the free single drug. CONCLUSION: The sul-HA nanoparticles for co-delivery of DOX and MIF could be a promising combined therapy strategy for the treatment of breast cancer.

The regenerating protein 3A: a crucial molecular with dual roles in cancer.

INTRODUCTION: REG3A, a member of the third subclass of the Reg family, has been found in a variety of tissues but is not detected in immune cells. In the past decade, it has been determined that REG3A expression is regulated by injury, infection, inflammatory stimuli, and pro-cytokines via different signaling pathways, and it acts as a tissue-repair, bactericidal, and anti-inflammatory molecule in human diseases. Recently, the role of REG3A in cancer has received increasing attention. The present article aims to investigate the structure, expression, regulation, function of REG3A, and to highlight the potential role of REG3A in tumors. METHODS: A detailed literature search and data organization were conducted to find information about the role of REG3A in variety of physiological functions and tumors. RESULTS: Contradictory roles of REG3A have been reported in different tumor models. Some studies have demonstrated that high expression of REG3A in cancers can be oncogenic. Other studies have shown decreased REG3A expression in cancer cells as well as suppressed tumor growth. CONCLUSIONS: Taken together, better understanding of REG3A may lead to new insights that make it a potentially useful target for cancer therapy.

Potential new targets and drugs related to histone modifications in glioma treatment.

Glioma accounts for 40-50% of craniocerebral tumors, whose outcome rarely improves after standard treatment. The development of new therapeutic targets for glioma treatment has important clinical significance. With the deepening of research on gliomas, recent researchers have found that the occurrence and development of gliomas is closely associated with histone modifications, including methylation, acetylation, phosphorylation, and ubiquitination. Additionally, evidence has confirmed the close relationship between histone modifications and temozolomide (TMZ) resistance. Therefore, histone modification-related proteins have been widely recognized as new therapeutic targets for glioma treatment. In this review, we summarize the potential histone modification-associated targets and related drugs for glioma treatment. We have further clarified how histone modifications regulate the pathogenesis of gliomas and the mechanism of drug action, providing novel insights for the current clinical glioma treatment. Herein, we have also highlighted the limitations of current clinical therapies and have suggested future research directions and expected advances in potential areas of disease prognosis. Due to the complicated glioma pathogenesis, in the present review, we have acknowledged the limitations of histone modification applications in the related clinical treatment.

Co-Delivery of Curcumin and Capsaicin by Dual-Targeting Liposomes for Inhibition of aHSC-Induced Drug Resistance and Metastasis.

Recent research studies have shown that the low survival rate of liver cancer is due to drug resistance and metastasis. In the tumor microenvironment (TME), activated hepatic stellate cells (aHSCs) have been proven to favor the development of liver cancer. Hence, the combination therapy dual-targeting aHSCs and tumor cells might be an effective strategy for treatment of liver cancer. In this study, the novel multifunctional liposomes (CAPS-CUR/GA&Gal-Lip) were prepared for co-delivery of curcumin (CUR) and capsaicin (CAPS), in which glycyrrhetinic acid (GA) and galactose (Gal) were chosen as targeting ligands to modify the liposomes (Lip) for dual-targeting liver cancer. To mimic TME, a novel HSCs+HepG2 (human hepatoma cell line) cocultured model was established for the antitumor effect in vitro. The results showed that, compared to HepG2 cells alone, the cocultured model promoted drug resistance and migration by upregulating the expression of P-glycoprotein (P-gp) and Vimentin, which were effectively inhibited by CAPS-CUR/GA&Gal-Lip. The efficacy of the in vivo antitumor was evaluated by three mice models: subcutaneous H22 (mouse hepatoma cell line) tumor-bearing mice, H22+m-HSC (mouse hepatic stellate cell) tumor-bearing mice, and orthotopic H22 cells-bearing mice. The results showed that CAPS-CUR/GA&Gal-Lip exhibited lesser extracellular matrix (ECM) deposition, lesser tumor angiogenesis, and superior antitumor effect compared with the no- and/or Gal-modified Lip, which was attributed to the simultaneous blocking of the activation of HSCs and inhibition of the metastasis of tumor cells. The dual-targeting method using Lip is thus a potential strategy for liver cancer treatment.

Rab3 is involved in cellular immune responses of the cotton bollworm, Helicoverpa armigera.

Rab3, a member of the Rab GTPase family, has been found to be involved in innate immunity. However, the precise function of this GTPase in innate immunity remains unknown. In this study, we identified a Rab3 gene (Ha-Rab3) from the cotton bollworm, Helicoverpa armigera and studied its roles in innate immune responses. Expression of Ha-Rab3 was upregulated in the hemocytes of H. armigera larvae after the injection of Escherichia coli or chromatography beads. The dsRNA-mediated knockdown of Ha-Rab3 gene in H. armigera larval hemocytes led to significant reduction in the phagocytosis and nodulation activities of hemocytes against E. coli, significant increase in the bacterial load in larval hemolymph, and significant reduction in the encapsulation activities of hemocytes toward invading chromatography beads. Furthermore, Ha-Rab3 knockdown significantly suppressed spreading of plasmatocytes. These results suggest that Ha-Rab3 plays important roles in H. armigera cellular immune responses, possibly by mediating spreading of hemocytes.

Effect of handball training on cognitive ability in elderly with mild cognitive impairment.

The aim was to examine the effect of handball training on cognitive ability in elderly with mild cognitive impairment. A total of 60 elderly were randomly divided into training group (n=30) and control group (n=30). The mini-mental state examination (MMSE) score and abilities of daily living scale (ADL) score before, after 3-month, and after 6-month intervention period was measured. The results showed that MMSE score was increased and ADL score was decreased in training group after 3-month and 6-month intervention (P<0.05), while there were no significant changes in MMSE or ADL in control group (P£3/40.05). These preliminary results indicated that handball training can improve cognitive ability in elderly with MCI.

SRP gene is required for Helicoverpa armigera prophenoloxidase activation and nodulation response.

SRP gene was first identified from the fall webworm, Hyphantria cunea as one of genes up-regulated after bacteria injection. A rent study in Spodoptera litura showed that stress-induced elevation of SRP expression highly correlates with reduced feeding activities and growth retardation of larvae. In this study, we identified a SRP gene from the cotton bollworm, Helicoverpa armigera, namely Ha-SRP, and studied its precise roles in insect immunity. Expressions of Ha-SRP were upregulated in H. armigera larval hemocytes after injection of Escherichia coli. When the expression of Ha-SRP in H. armigera larval hemocytes was inhibited by dsHa-SRP injection, the transcription of prophenoloxidase genes in hemocytes was repressed, phenoloxidase activity in bacteria-challenged larval hemolymph was significantly decreased, and nodule formation in bacteria-injected larvae was reduced. More importantly, RNAi-treated insects infected with E. coli showed higher bacterial growth in hemolymph compared with infected controls. These results suggest that Ha-SRP gene plays importance roles in H. armigera innate immunity, possibly by mediating prophenoloxidase activation and nodulation response.

Finite-element model for three-dimensional optical scattering problems.

We present a three-dimensional model based on the finite-element method for solving the time-harmonic Maxwell equation in optics. It applies to isotropic or anisotropic dielectrics and metals and to many configurations such as an isolated scatterer in a multilayer, bi-gratings, and crystals. We discuss the application of the model to near-field optical recording.