A retrospective study of paraganglioma of the urinary bladder and literature review.

Objective: To review and summarize the characteristics and therapy of paraganglioma of the urinary bladder (PUB). Method: Patients who underwent the operation in Peking Union Medical College Hospital between January 2012 and December 2021 were reviewed for this retrospective study. Results: A total of 29 patients, comprising 9 (31%) men and 20 (69%) women, were included. The main manifestations were hypertension, palpitation, and micturition syncope. Eight patients had an increased 24-h urinary catecholamine, and seven of them had increased norepinephrine. Normetanephrine in seven patients was increased. Six of 18 metaiodobenzylguanidine and 8 of 22 octreotide scans were positive. In total, 15 cases underwent laparoscopic partial cystectomy and 14 underwent transurethral resection of bladder tumor. In all patients, the immunohistochemical index of Melan-A, AE1/AE3, and α-inhibin were negative, and chromogranin A, S-100, and succinate dehydrogenase were positive. The Ki-67 of 28/29 cases was under 5%, and 1 case with a Ki-67 of 20% was diagnosed with malignant PUB. A total of 27 patients had a regular follow-up, 2 patients were lost during the follow-up, 3 patients had a recurrence, and 1 of these patients died within 1 year of surgery. The symptoms all disappeared or were relieved after the surgery. Conclusion: The transurethral surgery approach fits PUB tumors with a size <3 cm or that protrudes into the bladder and can significantly reduce the postoperative hospital stay. Early detection and treatment are effective, and regular review is necessary after the surgery.

Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective.

Numerous neurological disorders share a fatal pathologic process known as glutamate excitotoxicity. Among which, ischemic stroke is the major cause of mortality and disability worldwide. For a long time, the main idea of developing anti-excitotoxic neuroprotective agents was to block glutamate receptors. Despite this, there has been little successful clinical translation to date. After decades of "neuron-centered" views, a growing number of studies have recently revealed the importance of non-neuronal cells. Glial cells, cerebral microvascular endothelial cells, blood cells, and so forth are extensively engaged in glutamate synthesis, release, reuptake, and metabolism. They also express functional glutamate receptors and can listen and respond for fast synaptic transmission. This broadens the thoughts of developing excitotoxicity antagonists. In this review, the critical contribution of non-neuronal cells in glutamate excitotoxicity during ischemic stroke will be emphasized in detail, and the latest research progress as well as corresponding therapeutic strategies will be updated at length, aiming to reconceptualize glutamate excitotoxicity in a non-neuronal perspective.

Discovery of Novel PD-L1 Small-Molecular Inhibitors with Potent In Vivo Anti-tumor Immune Activity.

Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (X18: IC50 = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (X18: EC50 = 152.8 nM). Crystallographic studies revealed the binding mode of X18 and PD-L1. Through a rational prodrug design approach, we have successfully optimized the oral pharmacokinetic properties of X22, effectively addressing the poor oral pharmacokinetic profile of PD-L1 small-molecule inhibitors. Notably, X22 demonstrated significant antitumor efficacy in murine models of MC38 and CT26 colon cancer through the upregulation of tumor infiltration and cytotoxicity of CD8+ T cells partially. These findings offer promising prospects for the advancement of PD-L1 inhibitors as innovative agents in cancer immunotherapy.

Clonal integration of stress signal induces morphological and physiological response of root within clonal network.

Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.

Anisotropic mechanical properties of α-MoO3 nanosheets.

The mechanical behaviors of 2D materials are fundamentally important for their potential applications in various fields. α-Molybdenum trioxide (α-MoO3) crystals with unique electronic, optical, and electrochemical properties, have attracted extensive attention for their use in optoelectronic and energy conversion devices. From a mechanical viewpoint, however, there is limited information available on the mechanical properties of α-MoO3. Here, we developed a capillary force-assisted peeling method to directly transfer α-MoO3 nanosheets onto arbitrary substrates. Comparatively, we could effectively avoid surface contamination arising from the polymer-assisted transfer method. Furthermore, with the help of an in situ push-to-pull (PTP) device during SEM, we systematically investigated the tensile properties of α-MoO3. The measured Young's modulus and fracture strengths along the c-axis (91.7 ± 13.7 GPa and 2.1 ± 0.9 GPa, respectively) are much higher than those along the a-axis (55.9 ± 8.6 GPa and 0.8 ± 0.3 GPa, respectively). The in-plane mechanical anisotropy ratio can reach ∼1.64. Both Young's modulus and the fracture strength of MoO3 show apparent size dependence. Additionally, the multilayer α-MoO3 nanosheets exhibited brittle fracture with interplanar sliding due to poor van der Waals interaction. Our study provides some key points regarding the mechanical properties and fracture behavior of layered α-MoO3 nanosheets.

Exploration the mechanism of Shenling Baizhu San in the treatment of chronic obstructive pulmonary disease based on UPLC-Q-TOF-MS/MS, network pharmacology and in vitro experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. AIM OF THE STUDY: The objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. MATERIALS AND METHODS: First, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. RESULTS: A total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. CONCLUSIONS: The mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.

Efficacy and Safety of Traditional Chinese Medicines as a Complementary Therapy Combined With Chemotherapy in the Treatment of Gastric Cancer: An Overview of Systematic Reviews and Meta-Analyses.

BACKGROUND: In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. METHODS: SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. CONCLUSIONS: TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.

High-sensitivity piezoresistive sensors based on cellulose handsheets using origami-inspired corrugated structures.

Cellulose-based composites have attracted significant attention in the fabrication and advancement of wearable devices due to their sustainable, degradable, and cost-effective properties. However, achieving a cellulosic sensor with reliable sensory feedback remains challenging owing to the deficiency in reversible microstructures during response processes. In this study, we developed a piezoresistive sensor consisting of nearly pure cellulose handsheets using origami-inspired corrugated structures to achieve durable and sensitive piezoresistive responses. Multi-walled carbon nanotubes (MWCNTs) were used as conducting agents. With the addition of 7 wt% MWCNTs, 36.27 % of the cellulose fiber surface was covered and the conductivity of cellulose handsheets was increased to 8.7 S/m. The obtained conductive cellulose handsheets were transformed into corrugated structures and integrated orthogonally to construct the piezoresistive sensors with reversible electrical paths for electrons. The restorable corrugated structure endowed the sensors with a wide workable pressure range (0-10 kPa), high sensitivity (6.09 kPa-1 in a range of 0-0.92 kPa), fast response time (<280 ms), and good durability (>1000 cycles). Furthermore, the practical applications of the proposed sensors as wearable devices were demonstrated through phonation, real-time sports monitoring, and step pressure tests.

Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.

Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic interventions. The Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system of signaling pathways involved in I/R injury. This review article elucidates the underlying mechanisms involved in Wnt signaling, as well as the complex interplay between Wnt and other pathways, including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-ß, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca2+-Activin A, Hippo-Yes-associated protein, toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-ß, and hepatocyte growth factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, including apoptosis, the inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, and blood-brain barrier damage during I/R injury. Our comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery, while activation of the non-canonical Wnt pathways exacerbates injury. Moreover, we explore novel therapeutic approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, and clinical trials. The objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction, to facilitate the development of innovative therapeutic agents for I/R injury.

Relationship among α­synuclein, aging and inflammation in Parkinson's disease (Review).

Parkinson's disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging. In many cases, the complex interplay of numerous risk factors leads to the onset of PD. The mutated α-Syn gene, which expresses pathologicalα-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. α-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of α-Syn by glial cells, activation of inflammatory pathways by α-Syn in glial cells, transmission of α-Syn between glial cells and neurons, and interactions between peripheral immune cells and α-Syn. In addition to the aforementioned risk factors, PD may also be associated with aging, as the prevalence of PD increases with advancing age. The aging process impairs the cellular clearance mechanism, which leads to chronic inflammation and the accumulation of intracellular α-Syn, which results in DA neuronal death. In the present review, the age-associated α-Syn pathogenicity and the interactions between α-Syn and certain types of cells within the brain are discussed to facilitate understanding of the mechanisms of PD pathogenesis, which may potentially provide insight for the future clinical treatment of PD.

[Research progress on Huangqi Guizhi Wuwu Decoction and predictive analysis of quality markers].

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.

Carbon nanotubes: a powerful bridge for conductivity and flexibility in electrochemical glucose sensors.

The utilization of nanomaterials in the biosensor field has garnered substantial attention in recent years. Initially, the emphasis was on enhancing the sensor current rather than material interactions. However, carbon nanotubes (CNTs) have gained prominence in glucose sensors due to their high aspect ratio, remarkable chemical stability, and notable optical and electronic attributes. The diverse nanostructures and metal surface designs of CNTs, coupled with their exceptional physical and chemical properties, have led to diverse applications in electrochemical glucose sensor research. Substantial progress has been achieved, particularly in constructing flexible interfaces based on CNTs. This review focuses on CNT-based sensor design, manufacturing advancements, material synergy effects, and minimally invasive/noninvasive glucose monitoring devices. The review also discusses the trend toward simultaneous detection of multiple markers in glucose sensors and the pivotal role played by CNTs in this trend. Furthermore, the latest applications of CNTs in electrochemical glucose sensors are explored, accompanied by an overview of the current status, challenges, and future prospects of CNT-based sensors and their potential applications.

Comparative mitogenomic analysis of three bugs of the genus Hygia Uhler, 1861 (Hemiptera, Coreidae) and their phylogenetic position.

Hygia Uhler, 1861 is the largest genus in the bug family Coreidae. Even though many species of this genus are economically important, the complete mitogenomes of Hygia species have not yet been reported. Therefore, in the present study, the complete mitogenomes of three Hygia species, H.lativentris (Motschulsky, 1866), H.bidentata Ren, 1987, and H.opaca (Uhler, 1860), are sequenced and characterized, and submitted in a phylogenetic analysis of the Coreidae. The results show that mitogenomes of the three species are highly conserved, typically with 37 genes plus its control region. The lengths are 16,313 bp, 17,023 bp, and 17,022 bp, respectively. Most protein-coding genes (PCGs) in all species start with the standard codon ATN and terminate with one of three stop codons: TAA, TAG, or T. The tRNAs secondary structures of all species have a typical clover structure, except for the trnS1 (AGC) in H.bidentata, which lacks dihydrouridine (DHU) arm that forms a simple loop. Variation in the length of the control region led to differences in mitochondrial genome sizes. The maximum-likelihood (ML) and Bayesian-inference (BI) phylogenetic analyses strongly supported the monophyly of Hygia and its position within Coreidae, and the relationships are ((H.bidentata + (H.opaca + (H.lativentris + Hygia sp.))). The results provide further understanding for future phylogenetic studies of Coreidae.

p53 contributes to cardiovascular diseases via mitochondria dysfunction: A new paradigm.

Cardiovascular diseases (CVDs) are leading causes of global mortality; however, their underlying mechanisms remain unclear. The tumor suppressor factor p53 has been extensively studied for its role in cancer and is also known to play an important role in regulating CVDs. Abnormal p53 expression levels and modifications contribute to the occurrence and development of CVDs. Additionally, mounting evidence underscores the critical involvement of mitochondrial dysfunction in CVDs. Notably, studies indicate that p53 abnormalities directly correlate with mitochondrial dysfunction and may even interact with each other. Encouragingly, small molecule inhibitors targeting p53 have exhibited remarkable effects in animal models of CVDs. Moreover, therapeutic strategies aimed at mitochondrial-related molecules and mitochondrial replacement therapy have demonstrated their advantageous potential. Therefore, targeting p53 or mitochondria holds immense promise as a pioneering therapeutic approach for combating CVDs. In this comprehensive review, we delve into the mechanisms how p53 influences mitochondrial dysfunction, including energy metabolism, mitochondrial oxidative stress, mitochondria-induced apoptosis, mitochondrial autophagy, and mitochondrial dynamics, in various CVDs. Furthermore, we summarize and discuss the potential significance of targeting p53 or mitochondria in the treatment of CVDs.

Serum metabolomics probes the molecular mechanism of action of acupuncture on metabolic pathways related to glucose metabolism in patients with polycystic ovary syndrome-related obesity.

Polycystic ovary syndrome (PCOS) is a common endocrine syndrome, and obesity is the most common clinical manifestation. Acupuncture is effective in treating PCOS, but the differences in the biological mechanisms of acupuncture therapy and Western medicine treatment have not been determined. Thus, the purpose of this study was to find glucose metabolism-related pathways in acupuncture treatment and differentiate them from Western medical treatment. Sixty patients with PCOS-related obesity were randomly distributed into three groups: patients receiving (1) acupuncture treatment alone, (2) conventional Western medicine treatment, and (3) acupuncture combined with Western medicine treatment. A targeted metabolomics approach was used to identify small molecules and metabolites related to glucose metabolism in the serum of each group, and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze different metabolic fractions. The results showed acupuncture treatment modulates the activity of citric and succinic acids in the tricarboxylic acid cycle, regulates glycolytic and gluconeogenesis pathways, and improves the levels of sex hormones and energy metabolism. The intervention effects on the metabolic pathways were different between patients receiving combination therapy and patients receiving acupuncture therapy alone, suggesting that the dominant modulatory effect of Western drugs may largely conceal the efficacy of acupuncture intervention.

Carbon Nanotube-Directed 7 GPa Heterocyclic Aramid Fiber and Its Application in Artificial Muscles.

Poly(p-phenylene-benzimidazole-terephthalamide) (PBIA) fibers with excellent mechanical properties are widely used in fields that require impact-resistant materials such as ballistic protection and aerospace. The introduction of heterocycles in polymer chains increases their flexibility and makes it easier to optimize the fiber structure. However, the inadequate orientation of polymer chains is one of the main reasons for the large difference between the measured and theoretical mechanical properties of PBIA fibers. Herein, carbon nanotubes (CNTs) are selected as an orientation seed. Their structural features allow CNTs to orient during the spinning process, which can induce an orderly arrangement of polymers and improve the orientation of the fiber microstructure. To ensure the complete 1D topology of long CNTs (≈10 µm), PBIA is used as an efficient dispersant to overcome dispersion challenges. The p-CNT/PBIA fibers (10 µm single-walled carbon nanotube 0.025 wt%) exhibit an increase of 22% in tensile strength and 23% in elongation, with a maximum tensile strength of 7.01 ± 0.31 GPa and a reinforcement efficiency of 893.6. The artificial muscle fabricated using CNT/PBIA fibers exhibits a 34.8% contraction and a 25% lifting of a 2 kg dumbbell, providing a promising paradigm for high-performance organic fibers as high-load smart actuators.

Analysis of factors related to endometrial cancer in postmenopausal women with endometrial thickening.

OBJECTIVE: To investigate the factors related to endometrial cancer (EC) in postmenopausal women with endometrial thickening and the value of endometrial thickness (ET) in predicting EC. METHODS: A retrospective study of 385 referrals to our department for hysteroscopic diagnostic curettage assessment was carried out. Univariate analysis and multiple logistic regression analysis were used to identify the independent contributors to the development of EC. The ability of ET to predict EC was evaluated by receiver operating characteristic curve analysis. RESULTS: The follow-up period from the identification of endometrial thickening to pathological confirmation of EC was from 2 weeks to 3 months. In the postmenopausal bleeding (PMB) group, a total of 47 participants' specimens were pathologically malignant. Older age and polypoid mass-like lesions ( P < 0.001) were independent factors associated with EC. The optimal critical value of ET in predicting EC was 9.5 mm, with a sensitivity and specificity of 70.21% and 70.67%, respectively. In the non-PMB group, six participants had evidence of malignant pathology, and only polypoid mass-like lesions were an independent factor associated with EC ( P < 0.001). CONCLUSIONS: For postmenopausal women with increased ET and PMB, older age, thicker ET, and polypoid mass-like lesions on transvaginal ultrasound were independent associated factors for EC. An ET greater than 9.5 mm is a threshold for predicting EC. For postmenopausal women with increased ET without PMB, the incidence of endometrial malignancy is low. If the woman has polypoid mass-like lesions on transvaginal ultrasound, she should receive further attention.

The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art.

Ellagic acid (EA) is a kind of polyphenol compound extracted from a variety of herbs, such as paeoniae paeoniae, raspberry, Chebule, walnut kernel, myrrh, loquat leaf, pomegranate bark, quisquite, and fairy herb. It has anti-tumor, anti-oxidation, anti-inflammatory, anti-mutation, anti-bacterial, anti-allergic and multiple pharmacological properties. Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors, mainly through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, inhibiting tumor cell metastasis and invasion, inducing autophagy, affecting tumor metabolic reprogramming and other forms of anti-tumor efficacy. Its molecular mechanism is mainly reflected in inhibiting the proliferation of tumor cells through VEGFR-2 signaling pathway, Notch signaling pathway, PKC signaling pathway and COX-2 signaling pathway. PI3K/Akt signaling pathway, JNK (cJun) signaling pathway, mitochondrial pathway, Bcl-2 / Bax signaling pathway, TGF-ß/Smad3 signaling pathway induced apoptosis of tumor cells and blocked EMT process and MMP SDF1α/CXCR4 signaling pathway inhibits the metastasis and invasion of tumor cells, induces autophagy and affects tumor metabolic reprogramming to produce anti-tumor effects. At present, the analysis of the anti-tumor mechanism of ellagic acid is slightly lacking, so this study comprehensively searched the literature on the anti-tumor mechanism of ellagic acid in various databases, reviewed the research progress of the anti-tumor effect and mechanism of ellagic acid, in order to provide reference and theoretical basis for the further development and application of ellagic acid.

Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency. / é»„èŠªå¤šç³–é€šè¿‡è‚ é“èŒç¾¤å’ŒTLR4/NF-κBé€”å¾„å¯¹è„¾è™šæ°´æ¹¿ä¸åŒ–å¤§é¼ å ç–«åŠŸèƒ½ç´Šä¹±çš„è°ƒèŠ‚ä½œç”¨.

The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1ß (IL-1ß), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-|κB (TLR4/NF-|κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.