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The biological activities of water‐soluble components of edible mushroom Rubinoboletus ballouii (RB) were seldom reported. Polysaccharides of RB (RBP) were prepared and well‐characterized using chemical analyses. The immunomodulatory properties of RBP were investigated using human monocyte‐derived dendritic cells (moDC) in vitro, and cyclophosphamide (CTX)‐induced immunosuppressive mouse model. Results showed that RBP was found to contain 80.6% (w/w) of neutral sugars including D‐fucose, D‐mannose, D‐glucose and D‐galactose (1.7:1.4:1.0:1.8), and 12.5% (w/w) of proteins, which composed of glutamine, threonine, serine, etc. RBP could promote the maturation of moDC and increase the secretion of IL‐12p40, IL‐10, and TNF‐α. Furthermore, the stimulation of IL‐12p40 production was inhibited by pretreatment with toll‐like receptor (TLR)‐4 blocker or NF‐κB pathway blocker, suggesting that the activation of moDC by RBP was mediated through NF‐κB pathway via TLR‐4 receptor. On the other hand, in CTX‐treated mice, RBP restored the loss of CD34brightCD45dim hematopoietic stem cells and increased IL‐2 production in sera and splenocytes culture supernatant, as well as up‐regulated the percentage of CD4+ T helper lymphocyte in mice splenocytes. These findings strongly suggested that RBP are the active ingredients of RB responsible for its immunostimulatory actions and deserved to be further investigated as cancer supplements. [ABSTRACT FROM AUTHOR]

To improve the heat transfer capability and the crystallization property of the traditional mold flux, CaF2 was replaced with B2O3. Then, the influences of CeO2 on the heat transfer and the crystallization of the CaF2-bearing mold flux and the new mold flux with 10wt% B2O3 were studied using a slag film heat flux simulator and X-ray diffraction (XRD). The results revealed that the addition of CeO2 reduced the heat transfer by increasing the solid slag thickness and the crystallization of two mold fluxes. However, CeO2 had less effect on the B2O3-containing mold flux compared with the CaF2-bearing mold flux. According to the analyses, the CeO2 contents in the CaF2-bearing mold flux and the B2O3-containing mold flux should not exceed 8wt% and 12wt%, respectively. Therefore, these experimental results are beneficial to improve and develop the mold flux for casting rare earth alloy steels. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally identified to show potent anti-tumor activity and immunomodulatory capability. Unfortunately, several clinical studies of relevant cancer therapy did not observe significant response in maximum tolerated dose whether given alone or in combination. We have identified a tumor vasculature homing peptide (TCP-1 peptide) which targets only the vasculature of colorectal tumors but not normal blood vessels in animals and humans. In the current study, the antitumor effect of TCP-1/TNFα and TCP-1/IFNγ alone or in combination was studied in orthotopic colorectal tumor model.Methods: TCP-1/TNFα and TCP-1/IFNγ recombinant proteins were prepared and i.v. injected to study the in vivo anticancer effect in orthotopic colorectal tumor model. Tumor apoptosis was determined by TUNEL staining and cleaved caspase-3 immunofluorescent staining. Tumor infiltrating lymphocytes were analyzed by immunofluorescent staining and flow cytometry. Western-blot was performed to examine the expression of proteins. Cell apoptosis was measured by Annexin V/PI flow cytometry.Results: Targeted delivery of TNFα or IFNγ by TCP-1 peptide exhibited better antitumor activity than unconjugated format by inducing more tumor apoptosis and also enhancing antitumor immunity shown by increased infiltration of T lymphocytes inside the tumor. More importantly, combination therapy of TCP-1/TNFα and TCP-1/IFNγ synergistically suppressed tumor growth and alleviated systematic toxicity associated with untargeted therapy. This combination therapy induced massive apoptosis/secondary necrosis in the tumor.Conclusions: Taken together, our data demonstrate TCP-1 is an efficient drug carrier for targeted therapy of colorectal cancer (CRC). TCP-1/TNFα combined with TCP-1/IFNγ is a promising combination therapy for CRC. [ABSTRACT FROM AUTHOR]

This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance ( P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference ( P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype ( P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all considered to have no apparent effect in influencing the prognostic outcomes of advanced NSCLC patients receiving chemotherapy except lymph node metastasis ( P < 0.05). miR-SNP rs11077 of XPO5 may be independently connected with the prognosis and chemotherapy response of advanced NSCLC patients, and patients with AC genotype have relatively improved prognostic outcomes and better curative effect of chemotherapy than those with AA allele of XPO5. Further, lymph node metastasis may be also involved in influencing the prognosis of advanced NSCLC patients. [ABSTRACT FROM AUTHOR]

The calcium signaling plays a vital role in flow-dependent vascular endothelial cell (VEC) physiology. Variations in fluid shear stress and ATP concentration in blood vessels can activate dynamic responses of cytosolic-free $$\hbox {Ca}^{2+}$$ through various calcium channels on the plasma membrane. In this paper, a novel dynamic model has been proposed for transient receptor potential vanilloid 4 $$(\hbox {TRPV}_{4})\hbox {-C}_{1}$$ -mediated intracellular calcium dynamics in VECs induced by fluid shear stress and ATP. Our model includes $$\hbox {Ca}^{2+}$$ signaling pathways through P2Y receptors and $$\hbox {P2X}_{4} \,\hbox {Ca}^{2+}$$ channels (indirect mechanism) and captures the roles of the $$\hbox {TRPV}_{4}\hbox {-C}_{1}$$ compound channels in VEC $$\hbox {Ca}^{2+}$$ signaling in response to fluid shear stress (direct mechanism). In particular, it takes into account that the $$\hbox {TRPV}_{4}\hbox {-C}_{1}$$ compound channels are regulated by intracellular $$\hbox {Ca}^{2+}$$ and $$\hbox {IP}_{3}$$ concentrations. The simulation studies have demonstrated that the dynamic responses of calcium concentration produced by the proposed model correlate well with the existing experimental observations. We also conclude from the simulation studies that endogenously released ATP may play an insignificant role in the process of intracellular $$\hbox {Ca}^{2+}$$ response to shear stress. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) affects several joints but tends to be more prevalent in those that are weight-bearing, such as the knees, which are the most heavily loaded joints in the body. The incidence and disability rates of OA have continued to increase and seriously jeopardise the quality of life of middle-aged and older adults. However, OA is more than just a wear and tear disease; its aetiology is complex, and its pathogenesis is poorly understood. Metabolic syndrome (MetS) has emerged as a critical driver of OA development. This condition contributes to the formation of a distinct phenotype, termed metabolic syndrome-associated osteoarthritis (MetS-OA),which differs from other metabolically related diseases by its unique pathophysiological mechanisms and clinical presentation. As key mediators of MetS, metabolic adipokines such as leptin, lipocalin, and resistin regulate inflammation and bone metabolism through distinct or synergistic signaling pathways. Their modulation of inflammatory responses and bone remodeling processes plays a critical role in the pathogenesis and progression of OA. Due to their central role in regulating inflammation and bone remodeling, metabolic adipokines not only deepen our understanding of MetS-OA pathogenesis but also represent promising targets for novel therapeutic strategies that could slow disease progression and improve clinical outcomes in affected patients., Competing Interests: The authors declare that they have no competing interests., (© 2025 Zhang et al.)

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A ( cagA )-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP&#95;0888 , upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA , leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae , selectively enriched in the colons of H. pylori -pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium., Importance: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A ( cagA ). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies., Competing Interests: The authors declare no conflict of interest.

Ginsenoside Rb₁ (Rb₁), which is one of the main ingredients derived from Panax ginseng, has been found to have extensive pharmacological activities including antioxidant, anti-inflammatory, anticancer properties. In this study, the effect of Rb₁ on doxorubicin-induced myocardial autophagy was studied with H9c2 as the study object. CCK-8 method, transmission electron microscope observation, fluorescence staining observation and Western blot were used to detect changes in H9c2 cell proliferation and autophagy after treatment. According to the results, doxorubicin could cause cell viability decrease, significant increase in the LC3-Ⅱ/LC3-I ratio and down-regulation of the expression of p62. Pretreatment with ginsenoside Rb₁ inhibited cell viability decrease and increase in doxorubicin-induced autophagic structure and LC3-Ⅱ/LC3-I ratio, and down-regulation of the expression of p62. In conclusion, doxorubicin could induce H9c2 cell death and induce autophagy, and ginsenoside Rb₁ showed a protective effect on DOX-induced cardiotoxicity, which may be correlated with suppression of DOX-induced autophagy., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all considered to have no apparent effect in influencing the prognostic outcomes of advanced NSCLC patients receiving chemotherapy except lymph node metastasis (P < 0.05). miR-SNP rs11077 of XPO5 may be independently connected with the prognosis and chemotherapy response of advanced NSCLC patients, and patients with AC genotype have relatively improved prognostic outcomes and better curative effect of chemotherapy than those with AA allele of XPO5. Further, lymph node metastasis may be also involved in influencing the prognosis of advanced NSCLC patients.

Aberrant epigenetic reprogramming occurs frequently in the development of tumors. Histone H3 lysine 27 trimethylation (H3K27me3) exerts a repressive epigenetic mark on a large number of genes. UTX and JMJD3 are the only two histone demethylases which activate gene expression via demethylating H3K27me3 to H3K27me2 or H3K27me1. Current studies show that dysregulation of these two proteins are heavily linked to oncogenesis in various tissue types. Accumulating evidence suggested that there is remarkable therapeutic potential of targeting JMJD3 or UTX in different types of cancer. Herein, we shall give a brief review on the functional roles of JMJD3 and UTX in cancers and evaluate the available compounds and agents targeting UTX and JMJD3. Finally, we also discuss the several modalities that target UTX and JMJD3 for cancer therapy. This review will help to develop novel strategies to abolish or restore effects of UTX and JMJD3 in the pathogenesis of cancer.

Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in males and the second in females worldwide. Accumulating evidence has demonstrated that patients with chronic inflammation in bowels have an increased risk to develop CRC. Various inflammatory cells and mediators produced during chronic inflammation are orchestrated through different molecular signaling pathways and lead to the formation of a microenvironment in favor of tumorigenesis. Vascular endothelial growth factor (VEGF), which can be induced by chronic inflammation, plays a pivotal role in tumor angiogenesis as well as tumor growth and metastasis. Antiangiogenic therapy targeting VEGF and its signaling pathways represents a promising strategy to inhibit colorectal tumorigenesis. Indeed, anti-angiogenic agents modulating VEGF ligands and their receptors have already exhibited great potential in treating patients with CRC, especially when combined with conventional chemotherapeutic agents. This review discusses the promoting role of chronic inflammation in colorectal tumorigenesis at different stages including tumor initiation, promotion, progression and metastasis, highlighting the contributory role of VEGF in angiogenesis during the development from chronic inflammation to CRC. It also describes the clinical significance of anti- VEGF therapy in the treatment of such disease.

Objective: To investigate the association between aggressive behaviors and catechol-O-methyltransferase (COMT) single nucleotide polymorphism at position 158 from a valine to a methionine (Val158Met) as well as serotonin (5-HT) transporter gene linked polymorphic region (5-HTTLPR) in children., Methods: A total of 68 children who were exposed to domestic violence were recruited. The frequencies of genotypes and alleles of COMT Val158Met and 5-HTTLPR were examined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. A comparison was conducted between 24 children with high scores of aggressive problems and 44 control children with low scores of aggressive problems according to Child Behavior Checklist (for parents).ResultsThere were no significant differences in genotypes of COMT Val158Met (χ2=1.612, P=0.447) and 5-HTTLPR (χ2=1.807, P=0.405) between the two groups. There were also no significant differences in the frequencies of alleles of COMT Val158Met (χ2=1.648, P=0.119) and 5-HTTLPR(χ2=0.403, P=0.527) in the two groups., Conclusions: COMT Val158Met and 5-HTTLPR might not be the susceptible genes of children's aggression, suggesting that children's aggressive behaviors might be affected by multivariate factors.