A comparative study of PEO-PBO content on the targeting and anti-glioma activity of annonaceous acetogenins-loaded nanomicelles.

Annonaceous acetogenins (ACGs) have great potential in the treatment of gliomas, but are extremely insoluble and difficult for delivery in vivo. Poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) is an amphiphilic polymer and can reduce the clearance of nanoparticles by mononuclear phagocyte system. To explore an efficient and safe nanomedicine for glioma, ACGs-loaded nanomicelles (ACGs/EB-NCs) was constructed using PEO-PBO as a carrier, and the effect of PEO-PBO content on the targeting and anti-glioma activity were also compared. ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs, the three nanomicellels prepared with different ACGs/EB feeding ratios, had average particle sizes of 148.8±0.5 nm, 32.7±4.1 nm, and 27.1±0.3 nm, respectively. The three ACGs/EB-NCs were spherical in shape, with drug loading content close to the theoretical drug loading content, encapsulation efficiency greater than 97 %, and good stability in physiological media. The cumulative release rates of ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs were 78.2 %, 63.4 %, and 56.3 % within 216 hours, respectively. The inhibitory effects of three ACGs/EB-NCs on U87 MG cells were similar and stronger than free ACGs (P<0.05), with half inhibitory concentration of 0.17, 0.18, and 0.16 ng/mL (P>0.05), respectively. In U87 MG tumor­bearing mice, ACGs/EB5-NC, ACGs/EB10-NCs and ACGs/EB20-NCs showed a similar tumor inhibition rate of 61.1±5.9 %, 56.2±8.6 % and 64.3±9.4 % (P>0.05), with good safety. Three ACGs/EB-NCs exhibited excellent liver escape ability and tumor targeting ability, with the tumor targeting index greater than 1.5. Three ACGs/EB-NCs were successfully prepared with strong anti-glioma activity and tumor targeting properties, which are expected to provide new options for the clinical treatment of gliomas. The content of PEO-PBO in micelles did not have a significant effect on the tumor targeting and anti-glioma activity of ACGs/EB-NCs.

A Nomogram for Predicting the Effectiveness of Consultations on Multi-Drug Resistant Infections: An Exploration for Clinical Pharmacy Services.

Purpose: The increasing multi-drug resistance (MDR) is a serious threat to human health. The appropriate use of antibiotics can control the progression of MDR and clinical pharmacists play an important role in the rational use of antibiotics. There are many factors that influence the effectiveness of multi-drug resistant organisms (MDRO) infection consultations. The study aimed to establish a model to predict the outcome of consultation and explore ways to improve clinical pharmacy services. Patients and methods: Patients diagnosed with MDRO infection and consulted by clinical pharmacists were included. Univariate analysis and multivariate logistic regression analysis were used to identify independent risk factors for MDRO infection consultation effectiveness, and then a nomogram was constructed and validated. Results: 198 patients were finally included. The number of underlying diseases (OR=1.720, 95% CI: 1.260-2.348), whether surgery was performed prior to infection (OR=8.853, 95% CI: 2.668-29.373), ALB level (OR=0.885, 95% CI: 0.805~0.974), pharmacist title (OR=3.463, 95% CI: 1.277~9.396) and whether the recommendation was taken up (OR=0.117, 95% CI: 0.030~0.462) were identified as independent influences on the effectiveness of the consultation. The nomogram prediction model was successfully constructed and the AUC of the training set and the verification set were 0.849 (95% CI: 0.780-0.917) and 0.761 (95% CI: 0.616-0.907) respectively. The calibration curves exhibited good overlap between the data predicted by the model and the actual data. Conclusion: A nomogram model was developed to predict the risk of consultation failure and was shown to be good accuracy and good prediction efficiency, which can provide proactive interventions to improve outcomes for potentially treatment ineffective patients.

New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Endothelial dysfunction: Pathophysiology and therapeutic targets for sepsis-induced multiple organ dysfunction syndrome.

Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients.

Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair.

Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

Magnolia Officinalis Alcohol Extract Alleviates the Intestinal Injury Induced by Polygala Tenuifolia Through Regulating the PI3K/AKT/NF-κB Signaling Pathway and Intestinal Flora.

Purpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer's disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT. Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques. Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas). Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.

Enhanced anti-glioma activity of annonaceous acetogenins based on a novel liposomal co-delivery system with ginsenoside Rh2.

Annonaceous acetogenins (ACGs) have potent anti-tumor activity, and the problems of their low solubility, hemolysis, and in vivo delivery have been solved by encapsulation into nanoparticles. However, the high toxicity still limits their application in clinic. In this paper, the co-delivery strategy was tried to enhance the in vivo anti-tumor efficacy and reduce the toxic effects of ACGs. Ginsenoside Rh2, a naturally derived biologically active compound, which was reported to have synergistic effect with paclitaxel, was selected to co-deliver with ACGs. And due to its similarity with cholesterol in chemical structure, the co-loading liposomes, (ACGs + Rh2)-Lipo, were successfully constructed using Rh2 instead of cholesterol as the membrane material. The obtained (ACGs + Rh2)-Lipo and ACGs-Lipo had similar mean particle size (about 80 nm), similar encapsulation efficiency (EE, about 97%) and good stability. The MTS assay indicated that (ACGs + Rh2)-Lipo had stronger toxicity in vitro. In the in vivo study, in contrast to ACGs-Lipo, (ACGs + Rh2)-Lipo demonstrated an improved tumor targetability (3.3-fold in relative tumor targeting index) and significantly enhanced the antitumor efficacy (tumor inhibition rate, 72.9 ± 5.4% vs. 60.5 ± 5.4%, p < .05). The body weight change, liver index, and spleen index of tumor-bearing mice showed that Rh2 can attenuate the side effects of ACGs themselves. In conclusion, (ACGs + Rh2)-Lipo not only alleviated the toxicity of ACGs to the organism, but also enhanced their anti-tumor activity, which is expected to break through their bottleneck.

Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30.

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids.

Ameliorative effect of anisodamine (654-1/654-2) against myocardial dysfunction induced by septic shock via the NF-κB/NLRP-3 or the PI3K-AKT/NF-κB pathway.

BACKGROUND: Septic shock, an extremely dangerous condition that causes impairment of organ function, always largely contributes to mortality in intensive care units. The impact of septic shock-induced organ damage on morbidity and mortality is substantially influenced by myocardial dysfunction. However, it remains unclear whether and in what manner anisodamine (654-1/654-2) ameliorates myocardial dysfunction caused by septic shock. PURPOSE: This study is the pioneering investigation and validation about the protective efficacy of anisodamine (654-1/654-2) against LPS-induced myocardial dysfunction in septic shock rats. It also aims to explore the differences in the underlying molecular mechanisms of both drugs. METHODS: A septic shock model was established in SD rats by after tail vein administration of LPS. 64 rats were distributed into eight groups, such as LPS group, control group, LPS+654-1 group (1.25, 2.5, and 5 mg/kg), and LPS+654-2 group (1.25, 2.5, and 5 mg/kg). The hemodynamics, echocardiography, immunohistochemical analysis, TEM, TUNEL assay, and H&E staining were utilized to assess the septic shock model and myocardial function. Lactic acid, inflammatory markers (IL-1ß, IL-6, and TNF-α), endothelial injure markers (SDC-1, HS and TM) and myocardial injury markers (CK, c-TNT and NT-pro BNP) were assessed using ELISA or biochemical kits. Additionally, the mechanisms of 654-1/654-2 were analyzed using RNA-seq and bioinformatics, and validated using western blotting and RT-PCR. RESULTS: Administration of 654-1/654-2 significantly restored hemodynamics and improved myocardial and endothelial glycocalyx injury in septic shock rats. Furthermore, 654-1/654-2 dose-dependently reduced plasma levels of lactic acid, inflammatory cytokines, and markers of endothelial and myocardial injury. Analyses using RNA-seq, WB and RT-PCR techniques indicated that 654-1/654-2 could mitigate myocardial and endothelial injury by inhibiting the NF-κB and NLRP-3 pathways, and activating the PI3K-AKT pathway. CONCLUSIONS: These findings demonstrated that 654-1/654-2 could alleviate myocardial damage in septic shock rats. Specifically, 654-1 inhibited the NF-κB/NLRP-3 pathway, whereas 654-2 promoted the PI3K-AKT pathway and inhibited the NF-κB pathway, effectively mitigating the inflammatory response and cell apoptosis.

GC-MS Fingerprinting Combined with Chemical Pattern-Recognition Analysis Reveals Novel Chemical Markers of the Medicinal Seahorse.

Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang Dynasty. Hippocampus kelloggi (HK) is the most common seahorse species in the medicinal material market and is one of the genuine sources of medicinal seahorse documented in the Chinese pharmacopeia. It is mainly cultivated in the Shandong, Fujian, and Guangxi Provinces in China. However, pseudo-HK, represented by Hippocampus ingens (HI) due to its similar appearance and traits, is often found in the market, compromising the safety and efficacy of clinical use. Currently, there is a lack of reliable methods for identifying these species based on their chemical composition. In this study, we employed, for the first time, a strategy combining gas chromatography-mass spectrometry (GC-MS) fingerprints and chemical patterns in order to identify HK and HI; it is also the first metabolomic study to date of HI as to chemical components. The obtained results revealed remarkable similarities in the chemical fingerprints, while significant differences were also observed. By employing hierarchical cluster analysis (HCA) and principal component analysis (PCA), based on the relative contents of their characteristic peaks, all 34 samples were successfully differentiated according to their species of origin, with samples from the same species forming distinct clusters. Moreover, nonadecanoic acid and behenic acid were exclusively detected in HK samples, further distinguishing them from HI samples. Additionally, the relative contents of lauric acid, tetradecanoic acid, pentadecanoic acid, n-hexadecanoic acid, palmitoleic acid, margaric acid, oleic acid, fenozan acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) exhibited significant differences between HK and HI (p < 0.0001), as determined by an unpaired t-test. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified seven components (DHA, EPA, n-hexadecanoic acid, tetradecanoic acid, palmitoleic acid, octadecanoic acid, and margaric acid) with high discriminatory value (VIP value > 1). Thus, nonadecanoic acid, behenic acid, and these seven compounds can be utilized as chemical markers for distinguishing HK from HI. In conclusion, our study successfully developed a combined strategy of GC-MS fingerprinting and chemical pattern recognition for the identification of HK and HI, and we also discovered chemical markers that can directly differentiate between the two species. This study can provide a foundation for the authentication of Hippocampus and holds significant importance for the conservation of wild seahorse resources.

Gcn5- and Bre1-mediated Set2 degradation promotes chronological aging of Saccharomyces cerevisiae.

Loss of transcription-coupled histone H3 lysine 36 trimethylation (H3K36me3) contributes to shorter lifespans in eukaryotes. However, the molecular mechanism of the decline of H3K36me3 during aging remains poorly understood. Here, we report that the degradation of the methyltransferase Set2 is the cause of decreased H3K36me3 levels during chronological aging in budding yeast. We show that Set2 protein degradation during cellular senescence and chronological aging is mainly mediated by the ubiquitin-conjugating E2 enzyme Ubc3 and the E3 ligase Bre1. Lack of Bre1 or abolishment of the ubiquitination stabilizes Set2 protein, sustains H3K36me3 levels at the aging-related gene loci, and upregulates their gene expression, thus leading to extended chronological lifespan. We further illustrate that Gcn5-mediated Set2 acetylation is a prerequisite for Bre1-catalyzed Set2 polyubiquitination and proteolysis during aging. We propose that two sequential post-translational modifications regulate Set2 homeostasis, suggesting a potential strategy to target the Gcn5-Bre1-Set2 axis for intervention of longevity.

Alpinia katsumadai Hayata Volatile Oil Is Effective in Treating 5-Fluorouracil-Induced Mucositis by Regulating Gut Microbiota and Modulating the GC/GR Pathway and the mPGES-1/PGE2/EP4 Pathways.

This study was aimed to investigate the therapeutic effect and mechanism of AKHO on 5-fluorouracil (5-FU)-induced intestinal mucositis in mice. Mouse body weight, diarrhea score, and H&E staining were applied to judge the therapeutic effect of AKHO. 16S rDNA and nontargeted metabolomics have been used to study the mechanism. WB, ELISA, and immunohistochemistry were adopted to validate possible mechanisms. The results demonstrated that AKHO significantly reduced diarrhea scores and intestinal damage induced by 5-FU in mice. AKHO lowered the serum levels of LD and DAO, and upregulated the expressions of ZO-1 and occludin in the ileum. Also, AKHO upregulated the abundance of Lactobacillus in the gut and suppressed KEGG pathways such as cortisol synthesis and secretion and arachidonic acid metabolism. Further validation studies indicated that AKHO downregulated the expressions of prostaglandin E2 (PGE2), microsomal prostaglandin E synthase-1 (mPGES-1), and PGE2 receptor EP4, as well as upregulated the expression of glucocorticoid (GC) receptor (GR), leading to improved intestinal epithelial barrier function. Taken together, AKHO elicited protective effects against 5-FU-induced mucositis by regulating the expressions of tight junction proteins via modulation of GC/GR and mPGES-1/PGE2/EP4 pathway, providing novel insights into the utilization and development of this pharmaceutical/food resource.

Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity.

Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1ß, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.

Therapeutic potential of toosendanin: Novel applications of an old ascaris repellent as a drug candidate.

Toosendanin (TSN), extracted from Melia. toosendan Sieb.et Zucc. and Melia. azedarach L., has been developed into an ascaris repellent in China. However, with the improvement of public health protection, the incidence of ascariasis has been reduced considerably, resulting in limited medical application of TSN. Therefore, it is questionable whether this old ascaris repellent can develop into a drug candidate. Modern studies have shown that TSN has strong pharmacological activities, including anti-tumor, anti-botulinum, anti-viral and anti-parasitic potentials. It also can regulate fat formation and improve inflammation. These researches indicate that TSN has great potential to be developed into a corresponding medical product. In order to better development and application of TSN, the availability, pharmacodynamics, pharmacokinetics and toxicology of TSN are summarized systematically. In addition, this review discusses shortcomings in the current researches and provides useful suggestions about how TSN developed into a drug candidate. Therefore, this paper illustrates the possibility of developing TSN as a medical product, aimed to provide directions for the clinical application and further research of TSN.

Comparison of continuous pericapsular nerve group (PENG) block versus continuous fascia iliaca compartment block on pain management and quadriceps muscle strength after total hip arthroplasty: a prospective, randomized controlled study.

BACKGROUND: This investigation aimed to evaluate the impact of continuous pericapsular nerve group (PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip arthroplasty (THA). METHODS: This prospective, randomized, and controlled trial recruited a cohort of fifty-seven patients with unilateral femoral neck fractures from Xi'an Aerospace General Hospital in northwest China between July 2020 and November 2021. These patients were randomly assigned to two groups: the continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28). Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia, utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB. Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery. RESULTS: In the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia requirements compared to the FICB group. CONCLUSION: Continuous PENG block exhibited superior analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the affected side and facilitating early postoperative ambulation. TRIAL REGISTRATION: This clinical trial was registered in the China Clinical Trials Center ( http://www.chictr.org.cn ) on 20/07/2020, with the registration number ChiCTR2000034821.

Novel wine in an old bottle: Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases.

Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound ('old bottle') as a novel drug ('novel wine') for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.

Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor.

Ginsenosides are the major and key components for ginseng to exert its wide and beneficial therapeutic efficacy in clinic. Meanwhile, many ginsenosides and their metabolites showed in vitro an in vivo anti-tumor activity, among which ginsenoside Rb1 has attracted much attention due to its good solubility and amphipathy. In this study, the self-assembly behavior of Rb1 was investigated and the Rb1 nano-assembly could further stabilize or encapsulated hydrophobic drugs such as protopanaxadiol (PPD) and paclitaxel (PTX) to form nanoparticles, based on which, a natural nanoscale drug delivery system, ginsenoside Rb1 stabilized and PTX/PPD co-loaded nanoparticles (GPP NPs) were prepared. The resultant GPP NPs exhibited a small particle size of 126.2 nm, a narrow size distribution (PDI=0.145), and a zeta potential of -27.3 mV. PTX loading content was 11.06% with an encapsulation efficiency of 93.86%. GPP NPs were spherical and stable in normal saline, 5% glucose, PBS, plasma, or on-shelf storage for 7 days. Both PTX and PPD existed in an amorphous state in GPP NPs and were released in a sustained pattern. GPP NPs showed 10-fold higher in vitro anti-tumor activity of than PTX injections. In the in vivo experiment, GPP NPs achieved a much higher tumor inhibition rate than PTX injections (64.95% vs 43.17%, P < 0.01) and certain tumor target ability. In conclusion, GPP NPs had significantly enhanced anti-tumor efficacy and improved tumor microenvironment, thus were promising to be developed into a novel anti-tumor agent for the treatment of breast tumor.

Therapeutic potential of puerarin against cerebral diseases: From bench to bedside.

The incidence of cerebral diseases is rapidly increasing worldwide, and they have become an important challenge for modern medicine. Most of the available chemical drugs used in the treatment of cerebral diseases are highly toxic and single-targeted. Therefore, novel drugs from natural resources have attracted much attention for their potential to manage cerebral diseases. Puerarin is a natural isoflavone isolated from the roots of Pueraria species such as P. lobata (Willd.) Ohwi, P. thomsonii, and P. mirifica. Several authors have reported the beneficial effects of puerarin in cerebral ischemic disease, intracerebral hemorrhage, vascular dementia, Alzheimer's disease, Parkinson's disease, depression, anxiety, and traumatic brain injury. This review summarizes the brain pharmacokinetics, brain drug delivery system, clinical use (in cerebral diseases), toxicity, and the adverse clinical reactions of puerarin. We have systematically presented the pharmacological actions and the molecular mechanisms of puerarin in various cerebral diseases to provide a direction for future researches on the therapeutic use of puerarin in cerebral diseases.

Geographic Differentiation of Essential Oil from Rhizome of Cultivated Atractylodes lancea by Using GC-MS and Chemical Pattern Recognition Analysis.

The rhizome of Atractylodes lancea (RAL) is a well-known Chinese herbal medicine (CHM) that has been applied in clinical settings for thousands of years. In the past two decades, cultivated RAL has gradually replaced wild RAL and become mainstream in clinical practice. The quality of CHM is significantly influenced by its geographical origin. To date, limited studies have compared the composition of cultivated RAL from different geographical origins. As essential oil is the primary active component of RAL, a strategy combining gas chromatography-mass spectrometry (GC-MS) and chemical pattern recognition was first applied to compare the essential oil of RAL (RALO) from different regions in China. Total ion chromatography (TIC) revealed that RALO from different origins had a similar composition; however, the relative content of the main compounds varied significantly. In addition, 26 samples obtained from various regions were divided into three categories by hierarchical cluster analysis (HCA) and principal component analysis (PCA). Combined with the geographical location and chemical composition analysis, the producing regions of RAL were classified into three areas. The main compounds of RALO vary depending on the production areas. Furthermore, a one-way analysis of variance (ANOVA) revealed that there were significant differences in six compounds, including modephene, caryophyllene, γ-elemene, atractylon, hinesol, and atractylodin, between the three areas. Hinesol, atractylon, and ß-eudesmol were selected as the potential markers for distinguishing different areas by orthogonal partial least squares discriminant analysis (OPLS-DA). In conclusion, by combining GC-MS with chemical pattern recognition analysis, this research has identified the chemical variations across various producing areas and developed an effective method for geographic origin tracking of cultivated RAL based on essential oils.

Mechanism of Magnolia Volatile Oil in the Treatment of Acute Pancreatitis Based on GC-MS, Network Pharmacology, and Molecular Docking.

Objective: Magnoliae officinalis cortex (MOC) is one of the most frequently used traditional Chinese medicine (TCM) for the treatment of acute pancreatitis (AP). Magnolia volatile oil (MVO) is considered to be one of the main active ingredients in MOC for AP treatment. However, the underlying mechanism of MVO in AP therapy is unknown. Methods: An integrated strategy of gas chromatography-mass spectrum (GC-MS), network pharmacology, and molecular docking simulation was employed to predict underlying mechanism of MVO in AP treatment. First, the compounds of MVO were identified by GC-MS, and the targets of the identified characteristic compounds were collected from several databases, as well as AP-related targets. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to obtain the mechanism. Moreover, the binding activity between core therapeutic targets and their corresponding compounds was evaluated by molecular docking simulation. Results: GC-MS results showed a total of 35 compounds that appeared in at least 18 out of 20 chromatograms were considered as characteristic compounds of MVO, and 33 compounds of those were identified. Network analysis demonstrated that 33 compounds regulated 142 AP-related targets. Of those, 8 compounds (α-eudesmol, γ-eudesmol, (-)-terpinen-4-ol, terpineol, hinesol, linalool, borneol, and ß-eudesmol) and 8 targets (TNF, IL-1ß, PPARγ, PPARα, PTGS2, NCOA1, CNR1, and ESR1) have a close relationship with AP treatment and were recognized as the key active compounds and the core therapeutic targets, respectively. The 142 targets were involved in both inflammation and calcium overload-related biological pathways, such as neuroactive ligand-receptor interaction, estrogen, MAPK, and calcium signaling pathway. Moreover, molecular docking simulation indicated that the 8 core therapeutic targets strongly interacted with their corresponding compounds. Conclusions: In summary, the present study elucidated that the efficacy of MVO in AP treatment might be attributed to anti-inflammation and inhibition of calcium overload through multicomponents and multitargets.