[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Dual-Fuel Propelled Nanomotors with Two-Stage Permeation for Deep Bacterial Infection in the Treatment of Pulpitis.

Bacterial infection-induced inflammatory response could cause irreversible death of pulp tissue in the absence of timely and effective therapy. Given that, the narrow structure of root canal limits the therapeutic effects of passive diffusion-drugs, considerable attention has been drawn to the development of nanomotors, which have high tissue penetration abilities but generally face the problem of insufficient fuel concentration. To address this drawback, dual-fuel propelled nanomotors (DPNMs) by encapsulating L-arginine (L-Arg), calcium peroxide (CaO2 ) in metal-organic framework is developed. Under pathological environment, L-Arg could release nitric oxide (NO) by reacting with reactive oxygen species (ROS) to provide the driving force for movement. Remarkably, the depleted ROS could be supplemented through the reaction between CaO2 with acids abundant in the inflammatory microenvironment. Owing to high diffusivity, NO achieves further tissue penetration based on the first-stage propulsion of nanomotors, thereby removing deep-seated bacterial infection. Results indicate that the nanomotors effectively eliminate bacterial infection based on antibacterial activity of NO, thereby blocking inflammatory response and oxidative damage, forming reparative dentine layer to avoid further exposure and infection. Thus, this work provides a propagable strategy to overcome fuel shortage and facilitates the therapy of deep lesions.

Coupling of cylindrospermopsin and pho-harboring Verrucomicrobia supports the formation of Raphidiopsis blooms in low-phosphorus waters.

Cylindrospermopsin (CYN) can induce phytoplankton community to secrete alkaline phosphatase (ALP), which is one of the important strategies for the bloom-forming cyanobacterium Raphidiopsis to thrive in extremely low-phosphorus (P) waters. However, how bacterioplankton community, another major contributor to ALPs in waters, couples to Raphidiopsis through CYN, and the role of this coupling in supporting the dominance of Raphidiopsis in nature remain largely unknown. Here, we conducted microcosm experiments to address this knowledge gap, using a combination of differential filtration-based and metagenomics-based methods to identify the sources of ALPs. We found that, compared with algal-derived ALPs, bacteria-derived ALPs exhibited a more pronounced and sensitive response to CYN. This response to CYN was enhanced under low-P conditions. Interestingly, we found that Verrucomicrobia made the largest contribution to the total abundance of pho genes, which encode ALPs. Having high gene abundance of the CYN-sensing PI3K-AKT signaling pathway, Verrucomicrobia's proportion increased with higher concentrations of CYN under low-P conditions, thereby explaining the observed increase in pho gene abundance. Compared with other cyanobacterial genera, Raphidiopsis had a higher abundance of the pst gene. This suggests that Raphidiopsis exhibited a greater capacity to uptake the inorganic P generated by ALPs secreted by other organisms. Overall, our results reveal the mechanism of CYN-induced ALP secretion and its impact on planktonic P-cycling, and provide valuable insights into the role of CYN in supporting the formation of Raphidiopsis blooms.

Elucidation of Pharmacological Mechanism Underlying the Anti-Alzheimer's Disease Effects of Evodia rutaecarpa and Discovery of Novel Lead Molecules: An In Silico Study.

Alzheimer's disease (AD) is a brain disease with a peculiarity of multiformity and an insidious onset. Multiple-target drugs, especially Chinese traditional medicine, have achieved a measure of success in AD treatment. Evodia rutaecarpa (Juss.) Benth. (Wuzhuyu, WZY, i.e., E. rutaecarpa), a traditional Chinese herb, has been identified as an effective drug to cure migraines. To our surprise, our in silico study showed that rather than migraines, Alzheimer's disease was the primary disease to which the E. rutaecarpa active compounds were targeted. Correspondingly, a behavioral experiment showed that E. rutaecarpa extract could improve impairments in learning and memory in AD model mice. However, the mechanism underlying the way that E. rutaecarpa compounds target AD is still not clear. For this purpose, we employed methods of pharmacology networking and molecular docking to explore this mechanism. We found that E. rutaecarpa showed significant AD-targeting characteristics, and alkaloids of E. rutaecarpa played the main role in binding to the key nodes of AD. Our research detected that E. rutaecarpa affects the pathologic development of AD through the serotonergic synapse signaling pathway (SLC6A4), hormones (PTGS2, ESR1, AR), anti-neuroinflammation (SRC, TNF, NOS3), transcription regulation (NR3C1), and molecular chaperones (HSP90AA1), especially in the key nodes of PTGS2, AR, SLCA64, and SRC. Graveoline, 5-methoxy-N, N-dimethyltryptamine, dehydroevodiamine, and goshuyuamide II in E. rutaecarpa show stronger binding affinities to these key proteins than currently known preclinical and clinical drugs, showing a great potential to be developed as lead molecules for treating AD.

The efficacy of acupuncture for attention deficit hyperactivity disorder (ADHD): An overview of systematic reviews and meta-analyses.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common neurological and mental developmental disorders in children. Published systematic reviews (SRs) and meta-analyses (MAs) concerning the use of acupuncture for ADHD have compared the efficacy of acupuncture treatment to that of drug therapies. However, the quality of these articles has not been evaluated and the evidence varies widely. OBJECTIVE: To summarize and assess the efficacy of acupuncture for ADHD based on existing SRs and MAs. METHODS: A systematic search of the literature was conducted from inception until September 16 2021, using seven electronic databases. The AMSTAR-2 tool was used to evaluate the quality of SRs and MAs, and the GRADE system was used to assess the quality of evidence. RESULTS: There are a total of five SRs and MAs included in this overview. Using the AMSTAR-2, three articles were rated as having 'Low' quality, while two were rated as having of 'Critically Low' quality. The GRADE system was used to measure the quality of evidence for ten outcomes (five response rate outcomes, three Conners' Index of Hyperactivity (CIH) score outcomes, one Conners' rating scale score outcome, and one Chinese medicine syndrome outcome) across the five included MAs. Four of the ten outcomes demonstrated 'moderate' quality, four demonstrated 'low' quality, and two demonstrated 'very low' quality. The risk of bias and inconsistency accounted for most downgrading factors in the included reviews. CONCLUSION: It is still debatable whether acupuncture is efficacious in improving the CIH score and the Response rate. Considering the heterogeneity of clinical trials and the fact that this study did not search and evaluate the relevant data of each randomized controlled trial, large-sample and high-quality randomized controlled trials are still needed to draw reliable conclusions regarding acupuncture's role in treating ADHD. Due to the poor quality of existing available evidence, little inference can be drawn from the included studies.

[Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation].

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Mulberry extract ameliorates T2DM-related symptoms via AMPK pathway in STZ-HFD-induced C57BL/6J mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) is not only a tasty food but also a beneficial medicinal substance that has been historically used to treat diabetes, as recorded in Tang Ben Cao. Recent research on animal models has shown that the ethyl acetate extract of Morus alba L. fruits (EMF) has hypoglycemic and hypolipidemic properties. However, there is a lack of documentation on the specific mechanisms through which EMF exerts its hypoglycemic effects. OBJECTIVE OF THE STUDY: This study aimed to investigate the impact of EMF on L6 cells and C57/BL6J mice and to elucidate the potential mechanisms underlying its effects. The findings of this study can contribute to the existing evidence for the application of EMF as a therapeutic drug or dietary supplement in the management of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The UPLC-Q-TOF-MS technique was utilized to gather MS data. Masslynx 4.1 software in conjunction with the SciFinder database and other relevant references were used to analyze and identify the chemical composition of EMF. A series of in vitro investigations including MTT assay, glucose uptake assay and Western blot analysis were performed using an L6 cell model stably expressing IRAP-mOrange after EMF treatment. In vivo investigations were performed on a STZ-HFD co-induced T2DM mouse model, which included assessments of body composition, biochemical tests, histopathological analysis, and Western blot analysis. RESULTS: MTT results revealed that EMF had no toxic effects on the cells at various concentrations. When EMF was administered to L6 cells, there was an increase in glucose transporter type 4 (GLUT4) translocation activity and a significant dose-dependent enhancement of glucose uptake by L6 myotubes. EMF treatment led to a marked increase in P-AMPK levels and GLUT4 expression in the cells, but these effects were reversed by an AMPK inhibitor (Compound C). In diabetic mice with STZ-HFD-induced diabetes, EMF treatment improved oral glucose tolerance, hyperglycemia, and hyperinsulinemia. Furthermore, EMF supplementation significantly reduced insulin resistance (IR) in diabetic mice, as evaluated using a steady-state model of the insulin resistance index. Histopathological sections demonstrated that acute EMF treatment reduced hepatic steatosis, pancreatic damage, and adipocyte hypertrophy. Western blot analysis demonstrated that EMF treatment also reduced abnormally high PPARγ expression, elevated the level of p-AMPK and p-ACC, and augmented the abundance of GLUT4 in insulin-sensitive peripheral tissues. SUMMARY: The results suggest that EMF may exert beneficial effects on T2DM through the AMPK/GLUT4 and AMPK/ACC pathways, as well as by regulating PPARγ expression.

Isolation, purification, and mass spectrometry identification of the enzyme involved in citrus flavor (+)-valencene biotransformation to (+)-nootkatone by Yarrowia lipolytica.

BACKGROUND: (+)-Nootkatone is a highly valuable sesquiterpene compound that can be used as an aromatic in the food industry because of its grapefruit flavor and low sensory threshold. The unconventional yeast Yarrowia lipolytica has many unique physical and chemical properties, metabolic characteristics, and genetic structure, which has aroused the interest of researchers. Previous research showed that Y. lipolytica possesses the ability to transform the sesquiterpene (+)-valencene to (+)-nootkatone. The aim of this study was to isolate, purify, and identify the enzyme involved in the (+)-valencene bioconversion to (+)-nootkatone by Y. lipolytica. RESULTS: In this study, ultrasonic-assisted extraction, ammonium sulfate precipitation, anion-exchange chromatography, and gel-filtration chromatography were used to separate and purify the enzyme involved in the (+)-valencene bioconversion by Y. lipolytica. The protein was identified as aldehyde dehydrogenase (ALDH) (gene0658) using sodium dodecyl sulfate polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry analysis. The ALDH had the highest activity when the pH value was 6.0 and the temperature was 30 °C. The activity of ALDH was significantly stimulated by ferrous ions and inhibited by barium, calcium, and magnesium ions. CONCLUSION: This is the first time that ALDH was found to participate in (+)-valencene biotransformation by Y. lipolytica. It may be involved in regulating the microbial transformation of (+)-valencene to (+)-nootkatone through redox characteristics. This study provides a theoretical basis and reference for the biological synthesis of citrus flavor (+)-nootkatone. © 2023 Society of Chemical Industry.

Intestinal Escherichia coli and related dysfunction as potential targets of Traditional Chinese Medicine for respiratory infectious diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has saved countless lives and maintained human health over its long history, especially in respiratory infectious diseases. The relationship between the intestinal flora and the respiratory system has been a popular research topic in recent years. According to the theory of the "gut-lung axis" in modern medicine and the idea that "the lung stands in an interior-exterior relationship with the large intestine" in TCM, gut microbiota dysbiosis is a contributing factor to respiratory infectious diseases, and there is potential means for manipulation of the gut microbiota in the treatment of lung diseases. Emerging studies have indicated intestinal Escherichia coli (E. coli) overgrowth in multiple respiratory infectious diseases, which could exacerbate respiratory infectious diseases by disrupting immune homeostasis, the gut barrier and metabolic balance. TCM is an effective microecological regulator, that can regulate the intestinal flora including E. coli, and restore the balance of the immune system, gut barrier, and metabolism. AIM OF THE REVIEW: This review discusses the changes and effects of intestinal E. coli in respiratory infection, as well as the role of TCM in the intestinal flora, E. coli and related immunity, the gut barrier and the metabolism, thereby suggesting the possibility of TCM therapy regulating intestinal E. coli and related immunity, the gut barrier and the metabolism to alleviate respiratory infectious diseases. We aimed to make a modest contribution to the research and development of new therapies for intestinal flora in respiratory infectious diseases and the full utilization of TCM resources. Relevant information about the therapeutic potential of TCM to regulate intestinal E. coli against diseases was collected from PubMed, China National Knowledge Infrastructure (CNKI), and so on. The Plants of the World Online (https://wcsp.science.kew.org) and the Plant List (www.theplantlist.org) databases were used to provide the scientific names and species of plants. RESULTS: Intestinal E. coli is a very important bacterium in respiratory infectious diseases that affects the respiratory system through immunity, the gut barrier and the metabolism. Many TCMs can inhibit the abundance of E. coli and regulate related immunity, the gut barrier and the metabolism to promote lung health. CONCLUSION: TCM targeting intestinal E. coli and related immune, gut barrier, and metabolic dysfunction could be a potential therapy to promote the treatment and prognosis of respiratory infectious diseases.

Efficacy of Fufang E'jiao Jiang in the Treatment of Patients with Qi and Blood Deficiency Syndrome: A Real-World Prospective Multicenter Study with a Patient Registry.

Objective: This nationwide, multicenter prospective observational study with a patient registry was designed to evaluate the efficacy of Fufang E'jiao Jiang (FEJ) in Chinese patients with Qi and blood deficiency syndrome (QBDS). Methods: QBDS patients were consecutively recruited from 81 investigational sites in China from July, 2019, to December, 2020. Patients who met the eligibility criteria were enrolled in a prospective registry database. Baseline characteristics and changes in scores on the traditional Chinese medicine (TCM) symptom evaluation scale for Qi and blood deficiency, the clinical global impression (CGI) scale, the fatigue scale-14 (FS-14), and the Pittsburgh sleep quality index (PSQI) were analyzed to determine the clinical efficacy of FEJ. Results: A total of 3,203 patients were recruited. The average remission rate (i.e., the sum of the cure rate and improvement rate) of the 20 symptoms of QBDS was 92.49% after 4 weeks of FEJ treatment, which was higher than at baseline; the rate increased to 94.69% at 8 weeks. The CGI scale revealed that the number of total remissions at 4 and 8 weeks was 3,120 (97.41%) and 415 (100%), respectively. The total FS-14 scores decreased by 1.67 ± 4.11 (p < 0.001) at 4 weeks and 1.72 ± 3.09 (p < 0.001) at 8 weeks of treatment. The PSQI scores were 6.6 ± 4.7 and 6.52 ± 3.07 at 4 and 8 weeks, respectively, which were significantly lower than the baseline scores (p < 0.001; p = 0.0033). Both the subhealth fatigue (SF) and iron deficiency anemia (IDA) groups showed significantly improved clinical symptoms of QBDS (p < 0.01). Between-group comparisons revealed significantly greater improvements in FS-14 and PSQI scores in the SF group than in the IDA group (p < 0.05). A multivariate logistic regression analysis showed that disease course, FS-14 score at baseline, and four-week FEJ doses were independent risk factors for the degree of symptom relief in QBDS patients (p < 0.05). Conclusion: In real-world settings, FEJ has a promising effect in treating QBDS and can significantly improve the severity of its symptoms.

Physiological analysis and transcriptome sequencing of a delayed-green leaf mutant 'Duojiao' of ornamental crabapple (Malus sp.).

Malus spectabilis 'Duojiao' is a spontaneous delayed-green leaf color mutant of M. spectabilis 'Riversii' and has chloroplasts with irregularly arranged vesicles and indistinct stromal lamellae. The yellow leaves of mutant have less chlorophyll (Chl), carotenoids, and flavonoids. Measurement of photosynthetic gas exchange indicated that the mutant has lower photosynthetic activity than 'Riversii' plants. Transcriptome sequencing with the Illumina platform was used to characterize differences in gene expression between the leaves of plants with yellow and green colors and elucidate the molecular mechanisms responsible for variation in leaf color in ornamental crabapple. In the comparison group of mutant yellow leaves and the maternal green leaves, 1848 differentially significant expressed genes (DEGs) were annotated by transcriptomic analysis. Many DEGs and transcription factors were identified related to chloroplast development, Chl synthesis and degradation, photosynthesis, carotenoid biosynthesis, flavonoid biosynthesis and other pathways related to plant leaf color formation. Among these, the Chl biosynthesis-related coproporphyrinogen gene, oxidative decarboxylase gene, and Chl a oxygenase gene were down-regulated, indicating that Chl biosynthesis was blocked. GLK1, which regulates chloroplast development, was down-regulated in yellow leaves. Parallel experiments showed that the content of the Chl synthesis precursors, protoporphyrinogen IX, chlorophyllide a, and chlorophyllide b and the activity of chlorophyllogen III oxidase and chlorophyllide a oxygenase in the yellow leaves of 'Duojiao' were lower than those in the green leaves of 'Riversii'. Thus, leaf color formation is greatly affected by Chl metabolism and chloroplast development. The reliability of the RNA-sequencing data was confirmed by quantitative real-time PCR analysis with 12 selected DEGs. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01248-7.

Health-related quality of life in breast cancer patients in Asia: A meta-analysis and systematic review.

Objectives: The primary purposes of this meta-analysis and systematic review were to evaluate the health-related quality of life (HRQoL) of Asian breast cancer (BC) patients to understand their holistic HRQoL level and provide medical and nursing recommendations to improve and preserve their quality of life. Methods: A comprehensive literature search was conducted to find cross-sectional studies published in Chinese and English concerning HRQoL in BC patients from the inceptions of databases to 14 March 2022. The databases consulted were PubMed, Web of Science, Embase, Cochrane, PsyclNFO, CINAHL, and CNKI. Literature screening, data extraction, risk bias assessment, and data synthesis were independently carried out by two researchers. The Endnote X9 and Stata 15.0 software programs were used during the meta-analysis process. Results: Out of the 8,563 studies identified, 23 cross-sectional studies involving 3,839 Asian BC patients were included in this meta-analysis. Two tools, namely, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and Quality of Life Questionnaire Breast Cancer module 23 (EORTC QLQ-BR23)-were used to evaluate the HRQoL of BC patients in Asia. The pooled mean of the global health status of Asian BC patients was 58.34 (95% confidence interval [CI]: 53.66-63.02). According to functional subscales of EORTC QLQ-C30 and EORTC QLQ-BR23, Asian BC patients suffered from the worst emotional functioning (pooled mean=66.38; 95% CI: 59.66-73.11) and sexual enjoyment (pooled mean=49.31; 95% CI: 31.97-63.36). In addition, fatigue (pooled mean=42.17; 95% CI: 34.46-49.88) and being upset by hair loss (pooled mean=48.38; 95% CI: 36.64-60.12) were the most obvious symptoms that Asian BC patients experienced according to the meta-analysis results of the EORTC QLQ-C30 and EORTC QLQ-BR23 symptom subscales. Conclusion: Asian BC patients experience a relatively low HRQoL due to the prominent decline in their body functions, as well as the unpleasant experiences caused by their symptoms. It is suggested that timely, appropriate, and targeted intervention should be provided in relation to the physical, psychological, and social aspects of Asian BC patients' lives to enhance their ability to function, relieve them of adverse symptoms, and improve their overall HRQoL. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022321165.

Exploring the Effect and Mechanism of Si-Miao-Yong-An Decoction on Abdominal Aortic Aneurysm Based on Mice Experiment and Bioinformatics Analysis.

Background: Abdominal aortic aneurysm (AAA) is a fatal disease characterized by high morbidity and mortality in old population. Globally, effective drugs for AAA are still limited. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese medicine (TCM) formula with a high medical value, was reported to be successfully used in an old AAA patient. Thus, we reason that SMYAD may serve as a potential anti-AAA regime. Objective: The exact effects and detailed mechanisms of SMYAD on AAA were explored by using the experimental study and bioinformatics analysis. Methods: Firstly, C57BL/6N mice induced by Bap and Ang II were utilized to reproduce the AAA model, and the effects of SMYAD were systematically assessed according to histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Then, network pharmacology was applied to identify the biological processes, pathways, and hub targets of SMYAD against AAA; moreover, molecular docking was utilized to identify the binding ability and action targets. Results: In an animal experiment, SMYAD was found to effectively alleviate the degree of pathological expansion of abdominal aorta and reduce the incidence of Bap/Ang II-induced AAA, along with reducing the damage to elastic lamella, attenuating infiltration of macrophage, and lowering the circulating IL-6 level corresponding to the animal study, and network pharmacology revealed the detailed mechanisms of SMYAD on AAA that were related to pathways of inflammatory response, defense response, apoptotic, cell migration and adhesion, and reactive oxygen species metabolic process. Then, seven targets, IL-6, TNF, HSP90AA1, RELA, PTGS2, ESR1, and MMP9, were identified as hub targets of SMYAD against AAA. Furthermore, molecular docking verification revealed that the active compounds of SMYAD had good binding ability and clear binding site with core targets related to AAA formation. Conclusion: SMYAD can suppress AAA development through multicompound, multitarget, and multipathway, which provides a research direction for further study.

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy.

Intratumoral immunotherapeutic hydrogel administration is emerging as an effective method for inducing a durable and robust antitumor immune response. However, scaffold hydrogels that can synergize with the loaded drugs, thus potentiating therapeutic efficacy, are limited. Here, we report a ternary hydrogel composed of polyvinyl alcohol (PVA), polyethylenimine (PEI)‒a cationic polymer with potential immunoactivation effects, and magnesium ions‒a stimulator of the adaptive immune response, which exhibits an intrinsic immunomodulation function of reversing the immunologically "cold" phenotype of a murine breast tumor to a "hot" phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel (PEIGel) encapsulating an immune checkpoint blockade (ICB) inhibitor‒anti-PD-L1 antibody (α-PDL1) exhibits synergistic effects resulting in elimination of primary tumors and remote metastases and prevention of tumor relapse after surgical resection. A preliminary mechanistic study revealed a probably hidden role of PEI in modulating the polyamine metabolism/catabolism of tumors to potentiate the immune adjuvant effect. These results deepen our understanding of the innate immune activation function of PEI and pave the way for harnessing PEI as an immune adjuvant for ICB therapy.

Charge Reversal Polypyrrole Nanocomplex-Mediated Gene Delivery and Photothermal Therapy for Effectively Treating Papillary Thyroid Cancer and Inhibiting Lymphatic Metastasis.

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPRILK) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.

Four new polycyclic polyprenylated acylphloroglucinols from Hypericum wilsonii and their glucose uptake bioactivities.

Wilsonglucinols H-K (1-4), four new polycyclic polyprenylated acylphloroglucinols (PPAPs), and eight known compounds (5-12) were isolated and identified from the aerial parts of Hypericum wilsonii. Their planner structures were confirmed via extensive NMR and HRESIMS data analysis. The absolute configurations of the new compounds were mainly determined by NMR calculation and electronic circular dichroism (ECD) calculation. Compounds 1, 6, 8, and 10 showed glucose uptake activities at 30 µg/mL, in which compound 6 showed the strongest effect and increased the glucose uptake by 2.73 folds.

Sapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages.

Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 µM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with BMDMs, SA (10 µM) protected macrophages from the pyroptosis induced by APAP-damaged L02 cells. Moreover, SA treatment reduced the secondary liver cell damage aggravated by the conditioned medium (CM) taken from LPS/ATP-treated macrophages. The in vivo assessments conducted on mice pretreated with SA (25, 50 mg/kg, ip) then with a single dose of APAP (400 mg/kg, ip) showed that SA significantly alleviated inflammatory responses of AILI by inhibiting the expression and activation of the NLRP3 inflammasome. In general, the results reported herein revealed that SA exerts anti-inflammatory effects by regulating NLRP3 inflammasome activation in macrophages, which suggests that SA has great a potential for use in the treatment of AILI patients.

Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine-dependent SOD1 monomerization.

Endothelial cell apoptosis is an important pathophysiology in many cardiovascular diseases. The gasotransmitter nitric oxide (NO) is known to regulate cell survival and apoptosis. However, the mechanism underlying the effect of NO remains unclear. In this research, by targeting cytosolic copper/zinc superoxide dismutase (SOD1) monomerization, we aimed to explore how NO inhibited endothelial cell apoptosis. We showed that treatment with the NO synthase (NOS) inhibitor nomega-nitro-l-arginine methyl ester hydrochloride (L-NAME) significantly decreased the endogenous NO content of endothelial cells, facilitated the formation of SOD1 monomers, inhibited dismutase activity, and promoted reactive oxygen species (ROS) accumulation in human umbilical vein endothelial cells (HUVECs); by contrast, supplementation with the NO donor sodium nitroprusside (SNP) upregulated NO content, prevented the formation of SOD1 monomers, enhanced dismutase activity, and reduced ROS accumulation in L-NAME-treated HUVECs. Mechanistically, tris(2-carboxyethyl) phosphine hydrochloride (TCEP), a specific reducer of cysteine thiol, increased SOD1 monomer formation, thus preventing the NO-induced increase in dismutase activity and the decrease in ROS. Furthermore, SNP inhibited HUVEC apoptosis caused by the decrease in endogenous NO, whereas TCEP abolished this protective effect of SNP. In summary, our data reveal that NO protects endothelial cells against apoptosis by inhibiting cysteine-dependent SOD1 monomerization to enhance SOD1 activity and inhibit oxidative stress.

Protective effect of orange essential oil on the formation of non-alcoholic fatty liver disease caused by high-fat diet.

The purpose of this study was to investigate the protective effect of sniffing orange essential oil (OEO) on the formation of non-alcoholic fatty liver disease (NAFLD) caused by a high-fat diet. The results confirmed that sniffing OEO could reduce obesity caused by a high-fat diet (HFD) by reducing the levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In addition, the observation of liver tissue sections showed that sniffing OEO could reduce lipid accumulation in liver cells. Further analysis by western blot analysis showed that OEO treatment made the expression levels of acetyl-CoA carboxylase (ACC) and Cytochrome P450 2E1 (CYP2E1) down-regulated and the expression levels of peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyltransferase-1 (CPT-1) up-regulated. These results indicate that the treatment of sniffing OEO could enhance the antioxidant capacity of mice and reduce liver damage caused by a high-fat diet. Furthermore, sniffing OEO could inhibit lipid synthesis and oxidative stress stimulated by a high-fat diet. Overall, OEO treatment had a certain protective effect on NAFLD-related diseases caused by a high-fat diet. Therefore, aromatherapy may be introduced as a treatment of long-term chronic diseases.

Pulse Taking by a Piezoelectric Film Sensor via Mode Energy Ratio Analysis Helps Identify Pregnancy Status.

In order to solve the problem of non-invasive diagnosis and monitoring of women during pregnancy, a piezoelectric film pulse sensing system combined with the mode energy ratio (MER) analysis is utilized to detect human pulses to reveal pregnant conditions. Inspired by traditional Chinese medicine (TCM), pulse diagnosis has a history of more than 2,500 years. The life energy of the human body helps the diagnosis of the disease through the circulation of blood vessels connected to the organs. A PVDF piezoelectric film sensor is used to emulate the pulse taking process in TCM to record the pulse signals. And the algorithm of MER is proposed based on empirical mode decomposition (EMD). Through the MER analysis of 83 female volunteers with different pregnancy statuses, the identification and warning of pregnancy status and physical health indicators are realized.