Effects of ant nests on soil CH4 emissions from Syzygium oblatum communities of a secondary tropical forest.

Exploring the effects of ant nests on soil CH4 emissions in the secondary tropical forests is of great scientific significance to understand the contribution of soil faunal activities to greenhouse gas emissions. With static chamber-gas chromatography method, we measured the dry-wet seasonal dynamics of CH4 emissions from ant nests and control soils in the secondary forest of Syzygium oblatum communities in Xishuangbanna. We also examined the linkages of ant-mediated changes in functional microbial diversity and soil physicochemical properties with CH4 emissions. The results showed that: 1) Ant nests significantly accelerated soil CH4 emissions, with average CH4 emissions in the ant nests being 2.6-fold of that in the control soils. 2) The CH4 emissions had significant dry-wet seasonal variations, which was a carbon sink in the dry seasons (from -0.29±0.03 to -0.53±0.02 µg·m-2·h-1) and a carbon source in the wet seasons (from 0.098±0.02 to 0.041±0.009 µg·m-2·h-1). The CH4 emissions were significantly higher in ant nests than in control soils. The CH4 emissions from the ant nests had smaller dry-wet seasonal variation (from -0.38±0.01 to 0.12±0.02 µg·m-2·h-1) than those in the control soils (from -0.65±0.04 to 0.058±0.006 µg·m-2·h-1). 3) Ant nests significantly increased the values (6.2%-37.8%) of soil methanogen diversity (i.e., Ace and Shannon indices), temperature and humidity, carbon pools (i.e., total, easily oxidizable, and microbial carbon), and nitrogen pools (i.e., total, hydrolyzed, ammonium, and microbial biomass nitrogen), but decreased the diversity (i.e., Ace and Chao1 indices) of methane-oxidizing bacteria by 21.9%-23.8%. 4) Results of the structural equation modeling showed that CH4 emissions were promoted by soil methanogen diversity, temperature and humidity, and C and N pools, but inhibited by soil methane-oxidizing bacterial diversity. The explained extents of soil temperature, humidity, carbon pool, nitrogen pool, methanogen diversity, and methane-oxidizing bacterial diversity for the CH4 emission changes were 6.9%, 21.6%, 18.4%, 15.2%, 14.0%, and 10.8%, respectively. Therefore, ant nests regulated soil CH4 emission dynamics through altering soil functional bacterial diversities, micro-habitat, and carbon and nitrogen pools in the secondary tropical forests.

Risk factors for bacteremic pneumonia and mortality (28-day mortality) in patients with Acinetobacter baumannii bacteremia.

BACKGROUND: Patients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs. METHODS: A retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group. RESULTS: Among 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098-0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008-0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930-0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105-0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia. CONCLUSIONS: Our study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia.

Nanoparticle drug delivery systems responsive to tumor microenvironment: Promising alternatives in the treatment of triple-negative breast cancer.

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Effects of reverse osmosis membrane replacement of pure water system on clinical chemistry and immunoassay in clinical laboratory.

Introduction: Reverse osmosis (RO) membrane, key component of water-purifying equipment, is often stored in protection fluid containing substances such as glycerol, which may contaminate the water at replacement. This study aims to explore the effects of RO membrane replacement on clinical chemistry and immunoassay, particularly triglyceride (TG), providing reference for managing test interference caused by RO membrane replacement. Materials and methods: The RO membrane of water-purifying equipment A, which provided water to C16000 biochemistry analyzer (Abbott Laboratories, Abbott Park, USA) and E801 electrochemiluminescence analyzer (Roche, Basel, Switzerland), was replaced. Water resistivity was recorded, and quality control (QC) tests were performed on C16000 and E801. Moreover, TG was measured in 29 of selected serum samples on C16000 at 0.5h and 10.5h after RO membrane replacement and on reference biochemistry analyzer BS2000M (Mindray Biomedical Electronics Co., Shenzhen, China), which was connected to water-purifying equipment B without RO membrane replacement. Finally, blank, calibrator 1 and calibrator 2 of TG reagent were measured on C16000 before and at 0.5h, 2.5h and 10.5h after RO membrane replacement. All statistical analyses of data were done using GraphPad Prism (GraphPad Software Inc., San Diego, USA), and a value of P < 0.05 was considered statistically significant. Results: After RO membrane replacement, all QC results of clinical chemistry and immune tests passed except TG that showed positive bias of 536% and 371% at two levels, respectively. Moreover, TG results of the same serum samples were significantly higher at 0.5h than 10.5h after RO membrane replacement. Meanwhile, there was worse agreement and correlation of TG results between C16000 and BS2000M at 0.5h than 10.5h after replacement. Furthermore, the absorbance of TG blank, calibrator 1 and calibrator 2 was significantly higher at 0.5h and 2.5h after replacement than before replacement, and the absorbance gradually returned to normal value at 10.5h after replacement. Conclusions: Replacement of RO membrane could cause significant interference to TG test while have no effects on other laboratory tests performed in the study, which may be due to glycerol contamination. Our data provides important reference for management of test interference caused by RO membrane replacement. Clinical laboratory should observe the effects of RO membrane replacement on laboratory tests through both water quality monitoring and QC detection.

The mutual interactions among Helicobacter pylori, chronic gastritis, and the gut microbiota: a population-based study in Jinjiang, Fujian.

Objectives: Helicobacter pylori (H. pylori) is a type of bacteria that infects the stomach lining, and it is a major cause of chronic gastritis (CG). H. pylori infection can influence the composition of the gastric microbiota. Additionally, alterations in the gut microbiome have been associated with various health conditions, including gastrointestinal disorders. The dysbiosis in gut microbiota of human is associated with the decreased secretion of gastric acid. Chronic atrophic gastritis (CAG) and H. pylori infection are also causes of reduced gastric acid secretion. However, the specific details of how H. pylori infection and CG, especially for CAG, influence the gut microbiome can vary and are still an area of ongoing investigation. The incidence of CAG and infection rate of H. pylori has obvious regional characteristics, and Fujian Province in China is a high incidence area of CAG as well as H. pylori infection. We aimed to characterize the microbial changes and find potential diagnostic markers associated with infection of H. pylori as well as CG of subjects in Jinjiang City, Fujian Province, China. Participants: Enrollment involved sequencing the 16S rRNA gene in fecal samples from 176 cases, adhering to stringent inclusion and exclusion criteria. For our study, we included healthy volunteers (Normal), individuals with chronic non-atrophic gastritis (CNAG), and those with CAG from Fujian, China. The aim was to assess gut microbiome dysbiosis based on various histopathological features. QIIME and LEfSe analyses were performed. There were 176 cases, comprising 126 individuals who tested negative for H. pylori and 50 who tested positive defined by C14 urea breath tests and histopathological findings in biopsies obtained through endoscopy. CAG was also staged by applying OLGIM system. Results: When merging the outcomes from 16S rRNA gene sequencing results, there were no notable variations in alpha diversity among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and H. pylori positive [Hp (+)] and H. pylori negative [Hp (-)] groups. Beta diversity among different groups show significant separation through the NMDS diagrams. LEfSe analyses confirmed 2, 3, and 6 bacterial species were in abundance in the Normal, CNAG, and CAG groups; 26 and 2 species in the OLGIM I and OLGIM II group; 22 significant phylotypes were identified in Hp (+) and Hp (-) group, 21 and 1, respectively; 9 bacterial species exhibited significant differences between individuals with CG who were Hp (+) and those who were Hp (-). Conclusion: The study uncovered notable distinctions in the characteristics of gut microbiota among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and Hp (+) and Hp (-) groups. Through the analysis of H. pylori infection in CNAG and CAG groups, we found the gut microbiota characteristics of different group show significant difference because of H. pylori infection. Several bacterial genera could potentially serve as diagnostic markers for H. pylori infection and the progression of CG.

RNA Nanomedicine: Delivery Strategies and Applications.

Delivery of RNA using nanomaterials has emerged as a new modality to expand therapeutic applications in biomedical research. However, the delivery of RNA presents unique challenges due to its susceptibility to degradation and the requirement for efficient intracellular delivery. The integration of nanotechnologies with RNA delivery has addressed many of these challenges. In this review, we discuss different strategies employed in the design and development of nanomaterials for RNA delivery. We also highlight recent advances in the pharmaceutical applications of RNA delivered via nanomaterials. Various nanomaterials, such as lipids, polymers, peptides, nucleic acids, and inorganic nanomaterials, have been utilized for delivering functional RNAs, including messenger RNA (mRNA), small interfering RNA, single guide RNA, and microRNA. Furthermore, the utilization of nanomaterials has expanded the applications of functional RNA as active pharmaceutical ingredients. For instance, the delivery of antigen-encoding mRNA using nanomaterials enables the transient expression of vaccine antigens, leading to immunogenicity and prevention against infectious diseases. Additionally, nanomaterial-mediated RNA delivery has been investigated for engineering cells to express exogenous functional proteins. Nanomaterials have also been employed for co-delivering single guide RNA and mRNA to facilitate gene editing of genetic diseases. Apart from the progress made in RNA medicine, we discuss the current challenges and future directions in this field.

Flexible, Flame-Resistant, and Anisotropic Thermally Conductive Aerogel Films with Ionic Liquid Crystal-Armored Boron Nitride.

With the rapid development of miniaturization and high-power portable electronics, the accumulation of undesired heat can degrade the performance of electronic devices and even cause fires. Therefore, multifunctional thermal interface materials that combine high thermal conductivity and flame retardancy remain a challenge. Herein, an ILC (ionic liquids crystal)-armored boron nitride nanosheet (BNNS) with flame retardant functional groups was first developed. The high in-plane orientation structure aerogel film made of such an ILC-armored BNNS and aramid nanofiber and polyvinyl alcohol matrix through directional freeze-drying and mechanical pressing exhibits strong anisotropy thermal conductivity (λ// of 17.7 W m-1 K-1 and λ⊥ of 0.98 W m-1 K-1). In addition, the highly oriented IBAP aerogel films have excellent flame retardancy (peak heat release rate = 44.5 kW/m2 and heat release rate = 0.8 MJ/m2) due to the physical barrier effect and catalytic carbonization effect of ILC-armored BNNS. Meanwhile, IBAP aerogel films exhibit good flexibility and mechanical properties, even in harsh environments such as acids and bases. Further, IBAP aerogel films can also be used as a substrate for paraffin phase change composites. The ILC-armored BNNS provides a practical way to produce flame-resistant polymer composites with high thermal conductivity for TIMs in modern electronic devices.

Efficient Generation of Paired Single-Cell Multiomics Profiles by Deep Learning.

Recent advances in single-cell sequencing technology have made it possible to measure multiple paired omics simultaneously in a single cell such as cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-nucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq). However, the widespread application of these single-cell multiomics profiling technologies has been limited by their experimental complexity, noise in nature, and high cost. In addition, single-omics sequencing technologies have generated tremendous and high-quality single-cell datasets but have yet to be fully utilized. Here, single-cell multiomics generation (scMOG), a deep learning-based framework to generate single-cell assay for transposase-accessible chromatin (ATAC) data in silico is developed from experimentally available single-cell RNA-seq measurements and vice versa. The results demonstrate that scMOG can accurately perform cross-omics generation between RNA and ATAC, and generate paired multiomics data with biological meanings when one omics is experimentally unavailable and out of training datasets. The generated ATAC, either alone or in combination with measured RNA, exhibits equivalent or superior performance to that of the experimentally measured counterparts throughout multiple downstream analyses. scMOG is also applied to human lymphoma data, which proves to be more effective in identifying tumor samples than the experimentally measured ATAC data. Finally, the performance of scMOG is investigated in other omics such as proteomics and it still shows robust performance on surface protein generation.

Zinc deficiency compromises the maturational competence of porcine oocyte by inducing mitophagy and apoptosis.

Zinc, an essential trace mineral, plays a pivotal role in cell proliferation, maintenance of redox homeostasis, apoptosis, and aging. Serum zinc concentrations are reduced in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanism of the effects of zinc deficiency on the female reproductive system, especially oocyte quality, has not been fully elucidated. Thus, we established an in vitro experimental model by adding N,N,N',N'-Tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) into the culture medium, and to determine the potential regulatory function of zinc during porcine oocytes maturation. In the present study, we found that zinc deficiency caused aberrant meiotic progress, accompanied by the disrupted cytoskeleton structure in porcine oocytes. Zinc deficiency impaired mitochondrial function and dynamics, leading to the increase of reactive oxygen species (ROS) and acetylation level of the antioxidative enzyme superoxide dismutase 2 (SOD2), eventually induced the occurrence of oxidative stress and early apoptosis. Moreover, zinc deficiency perturbed cytosolic Ca2+ homeostasis, lipid droplets formation, demonstrating the aberrant mitochondrial function in porcine oocytes. Importantly, we found that zinc deficiency in porcine oocytes induced the occurrence of mitophagy by activating the PTEN-induced kinase 1/Parkin signaling pathway. Collectively, our findings demonstrated that zinc was a critical trace mineral for maintaining oocyte quality by regulating mitochondrial function and autophagy in porcine oocytes.

Activating caspase-8/Bid/ROS signaling to promote apoptosis of breast cancer cells by folate-modified albumin baicalin-loaded nanoparticles.

Abnormal apoptosis can lead to uncontrolled cell growth, aberrant homeostasis or the accumulation of mutations. Therapeutic agents that re-establish the normal functions of apoptotic signaling pathways offer an attractive strategy for the treatment of breast cancer. Baicalin (BA) is one of the natural compounds with anti-proliferation and pro-apoptosis activities against numerous tumor cells. However, low bioavailability restricts the clinical application of BA. In order to improve its therapeutic efficacy and study the mechanism of actions, active targeting delivery systems were developed for targeting tumor environment and selective cell killing effects. It emphasized on the construction of folate-conjugated albumin nanoparticles loaded with baicalin (FA-BSANPs/BA) and mechanisms of which on the promotion of breast cancer apoptosis. The physicochemical properties and structural characteristics of FA-BSANPs/BA were investigated. Cell experiments were carried out to study the targeted anti-breast cancer effects of FA-BSANPs/BA and its mechanism. The results showed that FA-BSANPs/BA was successfully constructed with stable structural characteristics and sustained release effects. Cellular uptake and MTT showed that it increased targeted uptake efficiency and cytotoxicity. Flow cytometry and western blot confirmed that it promoted apoptosis by increasing the expression of caspase-8 and ROS, and decreasing the level of Bid. It is suggested that the pro-apoptotic mechanism of FA-BSANPs/BA is related to regulation of key proteins in extrinsic apoptotic pathway. In conclusion, FA-BSANPs/BA is a good delivery carrier and significantly inhibits the breast cancer growth compared with free BA. The mechanism of FA-BSANPs/BA promoting apoptosis of breast cancer may be due to its action on the caspase-8/Bid/ROS pathway.

Study the mechanism of peimisine derivatives on NF-κB inflammation pathway on mice with acute lung injury induced by lipopolysaccharide.

Peimisine is one of the alkaloids in Fritillariae ussuriensis Bulbus, which has anti-acute lung injury effect. In order to obtain compounds with superior bio-activity, 14 new derivatives were obtained from peimisine, and the better activity compounds were screened by MTT method. It was found that boc-leucine mono peimisine ester monoamide (compound G, 25 µg/ml) had increased cell survival rate and reduced the TNF-α, IL-1ß, IL-6, and iNOS levels in RAW 264.7 by lipopolysaccharide (LPS)-stimulated. In vivo, LPS (10 mg/kg) was given intraperitoneally to establish ALI model, and compound G (2.5 or 10 mg/kg) was injected into mice as the experimental group. The results showed that after the compound G (10 mg/kg) treatment, the Wet / Dry ratio of the lung was reduced, and the expression of TNF-α, IL-1ß, IL-6 and iNOS was inhibited. Meanwhile, compound G (10 mg/kg) could increase the content of IκB protein and reduce the content of p65 protein in lung tissue by Western blot analysis, which may play an anti-acute lung injury role by inhibiting the activity of NF-κB signaling pathway. In conclusion, compound G could attenuate LPS-induced ALI in mice and it may become a new approach to treat ALI.

Long-term Follow-up of Pulsed Radiofrequency Treatment for Trigeminal Neuralgia: Kaplan-Meier Analysis in a Consecutive Series of 149 Patients.

BACKGROUND: At present, there is no ideal method for the treatment of trigeminal neuralgia (TN). The need for an easy, safe, non- or micro-neurodestructive, repeatable treatment, with a fairly satisfactory rate of pain relief, is paramount. Pulsed radiofrequency (PRF) as a minimally invasive and microdestructive technique has been reported to be an option for TN; however, no study has reported the long-term outcome of TN in a large case series. OBJECTIVES: We aimed to investigate the efficacy, safety, and the long-term outcomes of PRF treatment for patients with TN. STUDY DESIGN: This was a long-term, large case series, retrospective study. SETTING: The study was conducted at Tiantan hospital,Beijing. METHODS: We retrospectively analyzed medical databases and follow-up data of 149 patients with TN from January 2008 through March 2021, who underwent PRF treatment, with a median follow-up time of 71.0 months (interquartile range, 20.0 months to 112.0 months). Baseline characteristics and intraoperative data of patients were retrospectively extracted; data about complications and side effects were also collected. The follow-up data were composed of the postoperative Barrow Neurological Institute Pain Intensity Score  pain intensity at a different time, the onset time of PRF treatment, and the time when pain was recurrent. RESULTS: The initial pain relief rate was 75.17% after the procedure. The cumulative recurrence-free survival after the procedure was 75.00% at one month; 72.87% at 6 months; 70.59% at 12 months; 65.39% at 24 months; 61.63% 48 months; 56.73% at 96 months; and 49.64% at 144 months. The median recurrence-free time was 118 months according to the Kaplan-Meier estimator. Nineteen patients had pain recurrence with a median time of 15 months (range, 1.0 months to 96.0 months), among whom, 12 underwent a second PRF procedure and 9 patients experienced satisfactory pain relief. No serious complications or side effects occurred after the procedure. LIMITATIONS: This was a single-center, retrospective study. Our study failed to conduct a stratified analysis on the effect of PRF treatment for classic and idiopathic TN. The most efficacious parameters of PRF applied for TN and studies trying to identify positive predictive factors of pain relief before PRF treatment have yet to be investigated. CONCLUSIONS: The results of this study show the promising long-term effect of PRF on primary TN. The safety and repeatability might be more easily accepted by patients with TN and should be considered a preferred treatment option before choosing neurodestructive or more invasive methods.

Psoralen-loaded polymeric lipid nanoparticles combined with paclitaxel for the treatment of triple-negative breast cancer.

Background: Chemotherapeutic drugs are associated with toxic effects. Metastasis is the leading cause of death in breast cancer patients. Aim: To evaluate the antitumor effect of paclitaxel (PTX) combined with psoralen-loaded polymeric lipid nanoparticles (PSO-PLNs) in triple-negative breast cancer. Methods: After treatment of samples, cell viability, apoptosis, migration, invasion, expression of proteins in the IRAK1/NF-κB/FAK signal pathway, biodistribution and pathological characteristics were detected. Results: Compared with the control group, the PTX + PSO-PLNs group showed increased apoptosis and reduced migration, invasion and expression of phosphorylated IRAK1 and NF-κB, with significant inhibition of tumor growth and lung metastases and no obvious toxicity. Conclusion: Combined administration of PTX and PSO-PLNs exerted a synergistic effect and significantly inhibited the growth and metastasis of triple-negative breast cancer.

Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling.

Breast cancer is one of the top-ranked cancers for incidence and mortality worldwide. The biggest challenges in breast cancer treatment are metastasis and drug resistance, for which work on molecular evaluation, mechanism studies, and screening of therapeutic targets is ongoing. Factors that lead to inflammatory infiltration and immune system suppression in the tumor microenvironment are potential therapeutic targets. Interleukin-1 is known as a proinflammatory and immunostimulatory cytokine, which plays important roles in inflammatory diseases. Recent studies have shown that interleukin-1 cytokines drive the formation and maintenance of an inflammatory/immunosuppressive microenvironment through complex intercellular signal crosstalk and tight intracellular signal transduction, which were found to be potentially involved in the mechanism of metastasis and drug resistance of breast cancer. Some preclinical and clinical treatments or interventions to block the interleukin-1/interleukin-1 receptor system and its up- and downstream signaling cascades have also been proven effective. This study provides an overview of IL-1-mediated signal communication in breast cancer and discusses the potential of IL-1 as a therapeutic target especially for metastatic breast cancer and combination therapy and current problems, aiming at enlightening new ideas in the study of inflammatory cytokines and immune networks in the tumor microenvironment.

Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles.

OBJECTIVE: Our study aimed to find potential biomarkers for drug resistance in liver cancer cells using metabolomics and further to evaluate the potential of psoralen-loaded polymer lipid nanoparticles (PSO-PLNs) to reverse the resistance of cells to doxorubicin. METHODS: We used LC-MS-based non-targeted metabolomics, also known as global metabolite profiling, to screen in serum and urine of mice engrafted with a liver cancer cell line sensitive (HepG2/S) or resistant to doxorubicin (HepG2/ADR) for differentially regulated metabolites. We subsequently quantified the abundance of these metabolites in serum and the urine of mice. The mice were engrafted with HepG2 cells resistant against doxorubicin and were treated with I) doxorubicin, II) a combination of doxorubicin and psoralen and III) a combination of doxorubicin and psoralen packed in polymer lipid nanoparticles. RESULTS: Metabolites found to be differentially present in urine of mice engrafted with resistant HepG2 cells were: hippuric acid, hyaluronic acid, pantothenic acid, and betaine; retinoic acid and α-linolenic acid were found to be reduced in serum samples of mice with HepG2 cells resistant to doxorubicin. The targeted analysis showed that the degree of regression of metabolic markers in groups differed: treatment group 2 had stronger degree of regression than treatment group 1 and the negative control group had the smallest, which indicates that the PSO-PLNs have superior properties compared with other treatments. CONCLUSION: Psoralen reverses drug resistance of liver cancer cells and its efficacy can be increased by encapsulation in polymer lipid nanoparticles.

A review of nanoparticle drug delivery systems responsive to endogenous breast cancer microenvironment.

Breast cancer, as a malignant disease that seriously threatens women's health, urgently needs to be researched to develop effective and safe therapeutic drugs. Nanoparticle drug delivery systems (NDDS), provide a powerful means for drug targeting to the breast cancer, enhancing the bioavailability and reducing the adverse effects of anticancer drug. However, the breast cancer microenvironment together with heterogeneity of cancer, impedes the tumor targeting effect of NDDS. Breast cancer microenvironment, exerts endogenous stimuli, such as hypoxia, acidosis, and aberrant protease expression, shape a natural shelter for tumor growth, invasion and migration. On the basis of the ubiquitous of endogenous stimuli in the breast cancer microenvironment, researchers exploited them to design the stimuli-responsive NDDS, which response to endogenous stimulus, targeted release drug in breast cancer microenvironment. In this review, we highlighted the effect of the breast cancer microenvironment, summarized innovative NDDS responsive to the internal stimuli in the tumor microenvironment, including the material, the targeting groups, the loading drugs, targeting position and the function of stimuli-responsive nanoparticle drug delivery system. The limitations and potential applications of the stimuli-responsive nanoparticle drug delivery systems for breast cancer treatment were discussed to further the application.

Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal Cancer via Modulating the Composition of Gut Microbiota and Improving Intestinal Barrier.

Hunting for natural compounds that can modulate the structure of the intestinal flora is a new hotspot for colitis-associated cancer (CAC) prevention or treatment. Alisol B 23-acetate (AB23A) is a natural tetracyclic triterpenoid found in Alismatis rhizoma which is well known for dietary herb. Alismatis rhizoma is often used clinically to treat gastrointestinal diseases in China. In this study, we investigated the potential prevention of AB23A in male mouse models of azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC. AB23A intervention alleviated the body weight loss, disease activity index, colon tumor load, tissue injury, and inflammatory cytokine changes in CAC mice. AB23A intervention leads to remarkable reductions in the activation of TLR, NF-κB and MAPK. AB23A significantly decreased the phosphorylation of p38, ERK, and JNK and up-regulated mucin-2 and the expression of tight junction proteins. The gut microbiota of AB23A-interfered mice was characterized with high microbial diversity, the reduced expansion of pathogenic bacteria, such as Klebsiella, Citrobacter, and Akkermansia, and the increased growth of bacteria including Bacteroides, Lactobacillus, and Alloprevotella. These data reveal that AB23A has the potential to be used to treat CAC in the future.

Polymeric Lipid Hybrid Nanoparticles as a Delivery System Enhance the Antitumor Effect of Emodin in Vitro and in Vivo.

This study aimed to evaluate the therapeutic efficacy of Emodin-loaded polymer lipid hybrid nanoparticles (E-PLNs) for breast cancer. The size, Zeta potential, surface morphology, encapsulation efficiency, stability, in vitro drug release of E-PLNs prepared by the nanoprecipitation method were characterized. The uptake, in-vitro cytotoxicities and apoptosis of free drug, E-PLNs were investigated against MCF-7 cells. The efficacy of E-PLNs in tumor bearing nude mice has also been studied.The average particle size of the experimentally prepared E-PLNs was (122.7±1.79) nm, and the encapsulation rate was 72.8%. Compared with free Emodin (EMO), E-PLNs showed greater toxicity to MCF-7 cells by promoting the uptake of EMO, and can promote the early apoptosis of MCF-7 cells. In addition to the morphological changes of apoptotic cells, the ratio of Bax/Bcl-2 was significantly increased, which indicated that E-PLNs can induce apoptosis in MCF-7 cells to achieve anticancer effect. Finally, E-PLNs significantly inhibited tumor growth by more than 60%, which may be related to its passive targeting effect on tumor site. Our results suggest that E-PLNs have shown good anti-breast cancer effect than free EMO. Moreover, the effect of E-PLNs on MCF-7 cells is mainly related to the induction of apoptosis.

Alismatis Rhizoma Triterpenes Alleviate High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle of Mice.

Alismatis rhizoma (AR), which is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae), is an important component of many famous Chinese formulas for hypoglycemic. This study aimed to evaluate the insulin resistance (IR) alleviating effects of AR triterpenes (ART) and ART component compatibility (ARTC, the mixture of 16-oxo-alisol A, 16-oxo-alisol A 23-acetate, 16-oxo-alisol A 24-acetate, alisol C, alisol C 23-acetate, alisol L, alisol A, alisol A 23-acetate, alisol A 24-acetate, alisol L 23-acetate, alisol B, alisol B 23-acetate, 11-deoxy-alisol B and 11-deoxy-alisol B 23-acetate) in high-fat diet-induced IR mice and plamitate-treated IR C2C12 cells, respectively. A dose of 200 mg/kg of ART was orally administered to IR mice, and different doses (25, 50, and 100 µg/ml) of ARTC groups were treated to IR C2C12 cells. IPGTT, IPITT, body weight, Hb1AC, FFA, TNF-α, MCP-1, and IR-associated gene expression (p-AMPK, p-IRS-1, PI3K, p-AKT, p-JNK, and GLUT4) were measured in IR mice. Glucose uptake, TNF-α, MCP-1, and IR-associated gene expression were also measured in IR C2C12 cells. Results showed that ART alleviated high-fat diet-induced IR in the skeletal muscle of mice, and this finding was further validated by ARTC. This study demonstrated that ART presented a notable IR alleviating effect by regulating IR-associated gene expression, and triterpenes were the material basis for the IR alleviating activity of AR.

Role of inflammatory microenvironment: potential implications for improved breast cancer nano-targeted therapy.

Tumor cells, inflammatory cells and chemical factors work together to mediate complex signaling networks, which forms inflammatory tumor microenvironment (TME). The development of breast cancer is closely related to the functional activities of TME. This review introduces the origins of cancer-related chronic inflammation and the main constituents of inflammatory microenvironment. Inflammatory microenvironment plays an important role in breast cancer growth, metastasis, drug resistance and angiogenesis through multifactorial mechanisms. It is suggested that inflammatory microenvironment contributes to providing possible mechanisms of drug action and modes of drug transport for anti-cancer treatment. Nano-drug delivery system (NDDS) becomes a popular topic for optimizing the design of tumor targeting drugs. It is seen that with the development of therapeutic approaches, NDDS can be used to achieve drug-targeted delivery well across the biological barriers and into cells, resulting in superior bioavailability, drug dose reduction as well as off-target side effect elimination. This paper focuses on the review of modulation mechanisms of inflammatory microenvironment and combination with nano-targeted therapeutic strategies, providing a comprehensive basis for further research on breast cancer prevention and control.