To study the clinical characteristics of DUX4-IGH fusion B-cell acute lymphoblastic leukemia (B-ALL) in children in order to inform the diagnosis and treatment of this subtype.

Small nucleolar RNAs (snoRNAs) are a class of important non-coding RNAs traditionally involved in the modification and processing of ribosomal RNA. Recent studies have revealed that snoRNAs are aberrantly expressed in various gastrointestinal malignancies-including gastric cancer, colorectal cancer, and esophageal cancer-and contribute to tumorigenesis and progression by regulating gene expression and modulating key biological processes such as tumor cell proliferation, apoptosis, invasion, migration, metabolism, drug resistance, and stemness maintenance. Although extensive research has focused on the roles of snoRNAs in cancer, their precise molecular mechanisms and clinical utility remain incompletely understood. This review summarizes the expression profiles and functional mechanisms of snoRNAs in gastrointestinal cancers and discusses their potential as biomarkers or therapeutic targets, aiming to provide new insights for early diagnosis and precision therapy of these malignancies.

To investigate the regulatory role of lncRNA SNHG12 in docetaxel (DTX) resistance of prostate cancer (PCa) cells.

To explore the performance of a predictive model based on plasma multigene methylation testing in the early diagnosis of colorectal cancer (CRC).

This study aims to investigate the anti-gastric cancer effects and mechanisms of Actinidia eriantha polysaccharides(AEPS) through the regulation of energy metabolism. In the animal experiment, 615 mice were used to establish a subcutaneous gastric cancer xenograft model, and the modeled mice were allocated into a model group and low-(50 mg·kg~(-1)·d~(-1)) and high-dose(100 mg·kg~(-1)·d~(-1)) AEPS groups. AEPS was administered via intraperitoneal injection for 14 days, and the tumor volume was measured via a caliper. Targeted energy metabolomics analysis was conducted on the tumor tissue. In the cell experiment, human gastric cancer HGC-27 cells were allocated into a control group and low-, medium-, and high-dose AEPS-containing serum groups. The CCK-8, wound healing, and Transwell assays were employed to assess the cell viability, migration, and invasion, respectively. The adenosine triphosphate(ATP) content, reactive oxygen species(ROS) level, activities of pyruvate dehydrogenase(PDH) and alpha-ketoglutarate dehydrogenase(α-KGDH), and nicotinamide adenine dinucleotide(NADH) level were measured via corresponding kits. The protein level of hypoxia-inducible factor-1alpha(HIF-1α) was determined by Western blot. The results showed that compared with that in the model group, the tumor volume in the AEPS high-dose group was significantly reduced. Metabolomics analysis revealed significant differences in 17 metabolites between the AEPS and model groups. KEGG pathway enrichment indicated involvement of the tricarboxylic acid(TCA) cycle, arginine metabolism, and glucose metabolism. Notably, key TCA intermediates including citrate, isocitrate, malate, and α-ketoglutarate presented reduced levels in the AEPS group compared with the model group. The cell experiment showed that compared with the control group, AEPS-containing serum treatment reduced gastric cancer cell viability, especially in the medium-and high-dose groups(P<0.05, P<0.01), and inhibited cell migration and invasion(P<0.05, P<0.01, P<0.001). The AEPS-containing serum treatment decreased the ATP content, ROS levels, PDH and α-KGDH activities, and NADH levels, particularly in the high-dose group(P<0.01). The protein level of HIF-1α was upregulated in the high-dose AEPS group(P<0.05). These results indicate that AEPS inhibits the TCA cycle by downregulating the expression of PDH, α-KGDH, and NADH and reducing the levels of citrate, isocitrate, malate, and α-ketoglutarate, thereby disrupting energy metabolism reprogramming, lowering ATP and ROS production, and ultimately suppressing the viability, invasion, and migration of gastric cancer cells. The underlying molecular mechanism may be associated with regulation of HIF-1α expression.

This study aims to explore the inhibitory mechanism of Shuangshen Fuzheng Powder(SSG) on the tumor of mice bearing M1 macrophages and Lewis lung cancer cells. Lewis lung cancer cells and polarized RAW264.7 macrophages were mixed for injection to construct a mouse model with lung cancer xenograft. The mice were divided into a Lewis group, an SSG group, a Lewis + M1 macrophage(M1) group, and a Lewis + M1 + SSG group, with 10 mice in each group. The SSG group and the Lewis + M1 + SSG group were administered SSG suspension(208 mg·mL~(-1)) daily by gavage, and the Lewis group and the Lewis + M1 group were given purified water by gavage. The spleen and tumor samples were collected after three weeks of intervention. The volume and weight of subcutaneously transplanted tumors in mice were detected. The proportion of F4/80~+CD86~+ tumor-associated macrophages(TAMs) and the expression of CD206~+ in spleen cells were analyzed by flow cytometry, and the expression of M1 macrophage marker protein inducible nitric oxide synthase(iNOS) in transplanted tumor tissue was detected by immunohistochemical staining(IHC). The expression of iNOS, arginase 1(ARG1), transforming growth factor-β(TGF-β), vascular endothelial growth factor(VEGF), matrix metalloproteinase-9(MMP-9), and macrophage migration inhibition factor(MIF) in transplanted tumor tissue of mice was detected by Western blot(WB), and the chemical constituents of SSG were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HR-MS). The results showed that treatment by SSG and co-injection with M1 macrophages could both significantly inhibit the tumor volume and weight, and the inhibitory effects were similar. During treatment by SSG, the tumor burden in the Lewis + M1 + SSG group continued to decrease. The flow cytometry results showed that the SSG group and the Lewis + M1 + SSG group exhibited a significant increase in the CD86~+ expression and a significant decrease in the CD206~+ expression. The IHC results indicated that compared with that of the Lewis group, the expression of iNOS in the SSG group was significantly elevated. The WB assay results showed that the expression of iNOS protein significantly increased, and the expression of ARG1, TGF-β, VEGF, MMP-9, and MIF significantly decreased in the Lewis + SSG group compared with those of the Lewis group. A total of 125 chemical constituents were identified from SSG, mainly including saponins, flavonoids, nucleotides, amino acids, and sugar components. SSG may exert its inhibitory effect on lung cancer by increasing the polarization of macrophages to M1-type TAMs and reducing the polarization to M2-type TAMs. The analysis of the pharmacodynamic components of SSG provides a basis and reference for subsequent research on pharmacokinetics.

This study aims to investigate the mechanism by which the n-butanol fraction of Wenxia Formula extract(NWXF) reverses cisplatin(DDP) resistance in lung cancer via targeting cancer-associated fibroblasts(CAFs)-mediated regulation of glutathione(GSH) synthesis. A combined in vivo and in vitro experimental approach was employed to examine the therapeutic effects and molecular mechanisms of NWXF in ameliorating DDP resistance: a subcutaneous tumor xenograft model in nude mice was established in vivo. The mice injected with non-small cell lung cancer cells(A549) were randomly divided into control group and DDP group, while those injected with A549+CAFs cells were divided into CAFs group, CAFs+DDP group, NWXF+CAFs group, and NWXF+CAFs+DDP group. Hematoxylin-eosin(HE) staining was utilized to observe tumor histomorphological changes. TUNEL staining and immunohistochemistry were employed to detect tumor apoptosis. DTNB assay was used to measure the GSH level, and Western blot was employed to detect expressions of glutamate-cysteine ligase catalytic subunit(GCLc), glutamate-cysteine ligase regulatory subunit(GCLm), and recombinant solute carrier family 7 member 11(SLC7A11) proteins. A conditioned co-culture model with A549 cells was constructed in vitro. Cell counting kit-8(CCK-8) assay was employed to detect A549 cell proliferation, and flow cytometry was used to measure apoptosis. DTNB was used to determine the levels of GSH and cysteine(Cys), and Western blot was utilized to examine the expressions of GCLc, GCLm, and SLC7A11 proteins. In vivo results demonstrated that compared to the CAFs+DDP group, the NWXF+CAFs+DDP group exhibited markedly reduced tumor volume, significant tumor necrosis, obviously increased apoptosis, and apparently downregulated GSH level and expressions of GCLc, GCLm, and SLC7A11 proteins. In vitro results showed that the IC_(50) of DDP in A549 was significantly declined under the conditioned medium treated with NWXF. Compared to the CAFs-CM+DDP group, the NWXF-CAFs-CM+DDP group displayed significantly increased apoptosis, significantly decreased levels of GSH and Cys, and significantly downregulated expressions of GCLc, GCLm, and SLC7A11 proteins. In conclusion, NWXF may ameliorate resistance to DDP in lung cancer by inhibiting CAFs-mediated GSH synthesis.

This study explored the therapeutic potential and underlying mechanisms of betulinic acid(BA) in the treatment of colorectal cancer(CRC) through integrated bioinformatics analysis and in vitro experimental validation. Potential targets of BA against CRC were identified by mining multiple public databases, including BATMAN-TCM, PharmMapper, DrugBank, and GeneCards. A total of 100 overlapping targets were identified. Protein-protein interaction(PPI) network was constructed to screen for core targets. Differentially expressed genes(DEGs) in CRC patients were obtained from the cancer genome atlas(TCGA), and single-cell RNA sequencing analysis was employed to identify the specific cell clusters potentially affected by BA. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the common targets to clarify the potential signaling pathways and biological processes. Core targets were further validated through molecular docking with BA. A methyltransferase-like 3(METTL3) knockdown model was established using HCT116 colorectal cancer cells. The cells were treated with varying concentrations of BA(9.375, 18.75, 37.5, 75, and 150 μmol·L~(-1)). Cell viability was assessed using CCK-8 assay. Additionally, wound healing assays were used to assess cell migration ability, while Transwell assays were conducted to evaluate both migration and invasion ability. Western blot analysis was performed to measure the expression levels of METTL3, as well as peroxisome proliferator-activated receptors(PPAR)γ and PPARα. Network pharmacology analysis revealed that the therapeutic effects of BA on CRC were primarily associated with 100 therapeutic targets and 26 signaling pathways, with PPAR signaling pathway identified as a key pathway. Molecular docking demonstrated that BA exhibited a strong binding affinity to the core targets. In vitro experiments confirmed that BA significantly inhibited the proliferation, migration, and invasion of HCT116 cells. Western blot indicated that BA treatment downregulated METTL3 expression and reduced the expression of PPARγ and PPARα compared to the control group. These findings suggest that BA may inhibit the proliferation, migration, and invasion of CRC cells by down-regulating METTL3 expression, thereby reducing the m~6A methylation level of PPARγ and PPARα mRNA, leading to decreased mRNA stability and translational efficiency, and ultimately modulating the PPAR signaling pathway.

This study investigated the mechanism by which total flavonoids from Sarcandra glabra promote apoptosis in leukemia K562 cells using cellular metabolomics. The following groups were set up in this study: a blank control group, a dimethyl sulfoxide(DMSO) control group, and low-, medium-, and high-dose S. glabra total flavonoid groups(25, 50, and 100 mg·L~(-1)). After 48 hours of treatment, the effects of total flavonoids from S. glabra on the proliferation and apoptosis of K562 cells were assessed using chemiluminescence assay kits and flow cytometry. Untargeted metabolomics was employed to analyze differential metabolites between the DMSO control group and the high-dose total flavonoids from S. glabra group, followed by metabolic pathway enrichment analysis. Key metabolic and signaling pathways were identified through integrated analysis of differential metabolites and transcriptomics-derived differentially expressed genes. Molecular docking was conducted to analyze target interactions between key metabolites and signaling pathways, and protein expression was validated by Western blot. The results showed that, compared with the DMSO control group, both medium-and high-dose total flavonoids from S. glabra significantly suppressed K562 cell viability and promoted apoptosis. A total of 158 differential metabolites were identified by untargeted metabolomics. The top five metabolic pathways most responsive to total flavonoids from S. glabra were sphingolipid metabolism, glutathione metabolism, arginine and proline metabolism, histidine metabolism, and lysine degradation. Integrated analysis indicated that sphingolipid metabolism and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway were the most significantly affected. Key metabolites in the sphingolipid metabolism pathway, i.e., dihydroceramide, ceramide, and sphingosine, showed binding energies with PI3K/Akt below-5.0 kcal·mol~(-1). Western blot results confirmed that total flavonoids from S. glabra significantly suppressed the levels of p-PI3K/PI3K and p-Akt/Akt in K562 cells. In conclusion, total flavonoids from S. glabra promote apoptosis in leukemia K562 cells by regulating sphingolipid metabolism and inhibiting the PI3K/Akt signaling pathway.

This study aimed to investigate the inhibitory effect of periplogenin(PPG) on bladder cancer cells and elucidate its anti-tumor mechanism via the induction of ferroptosis. The effects of PPG on the proliferation of T24 and MBT-2 bladder cancer cells were assessed using cell counting kit-8(CCK-8) and 5-ethynyl-2'-deoxyuridine(EdU) assays. Ferroptosis was evaluated by measuring the glutathione/oxidized glutathione(GSH/GSSG) ratio, Fe~(2+), and malondialdehyde(MDA) levels, as well as mitochondrial superoxide production using the MitoSOX~(TM) Red fluorescent probe. Western blot and immunofluorescence were performed to detect the expression of ferroptosis-related proteins, including heme oxygenase 1(HMOX1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and nuclear factor erythroid 2-related factor 2(Nrf2). The regulatory mechanism of PPG on Nrf2 was further investigated using cycloheximide(CHX) to inhibit de novo protein synthesis, the proteasome inhibitor MG132 to block proteasomal degradation, and co-immunoprecipitation to assess Nrf2 ubiquitination. A mouse xenograft model was established by subcutaneously injecting MBT-2 cells into BALB/C mice. The animals were randomly divided into a control group and two PPG treatment groups(low-dose: 10 mg·kg~(-1); high-dose: 20 mg·kg~(-1)). Starting from day 5 when tumors became palpable, PPG was administered once daily for 30 consecutive days. Tumor growth was monitored, and the expression of Ki67, GPX4, and Nrf2 in tumor tissues was analyzed by immunohistochemistry. Compared with the control group, PPG significantly inhibited proliferation and reduced the viability of T24 and MBT-2 cells. PPG treatment led to a significant reduction in the GSH/GSSG ratio, while Fe~(2+) and MDA levels were markedly increased, along with enhanced mitochondrial superoxide generation, suggesting the induction of ferroptosis. Western blot and immunofluorescence results showed that PPG significantly downregulated the expression of HMOX1, SLC7A11, GPX4, and Nrf2. CHX and MG132 treatments, along with ubiquitination assays, demonstrated that PPG promoted Nrf2 ubiquitination and proteasomal degradation. In vivo, PPG significantly suppressed tumor growth and reduced the expression of Ki67, GPX4, and Nrf2 in xenograft tumors compared with the control group. PPG induces ferroptosis in bladder cancer cells by promoting Nrf2 ubiquitination and proteasomal degradation, thereby inhibiting tumor cell growth.

Chronic atrophic gastritis(CAG) represents a critical precancerous stage in gastric carcinogenesis, and its pathogenesis involves circadian rhythm disruption, chronic inflammation, and lipid metabolism reprogramming. Employing an integrative Chinese-western medical approach, this study systematically elucidated the molecular mechanisms whereby the core circadian clock gene BMAL1 promotes "inflammation to cancer" transformation through modulating the HIF-1α-FABP axis, driving lipid metabolism reprogramming, exacerbating oxidative stress, and disrupting immune homeostasis. The study revealed that compound traditional Chinese medicine(TCM) formulas(including Huangqi Jianzhong Tang, Xianglian Huazhuo Fang, and Lizhong Tang) intervened in the BMAL1-mediated "circadian-metabolic-immune" network, significantly ameliorated pathological damage to the gastric mucosa, suppressed inflammatory responses, alleviated lipid metabolism disorder, and reversed the "inflammation to cancer" transformation through multi-target effects. The TCM concept of "Taiyin disease resolution period"(21:00-03:00) gave insights into the link between spleen and stomach functions and circadian rhythms, with its therapeutic time window exhibiting remarkable synchronization with BMAL1 expression rhythms. Clinical studies further demonstrated that chronotherapy strategies based on chronopharmacological principles can significantly enhance the therapeutic efficacy of TCM. Based on these findings, the theory of "Taiyin disease resolution period" provides guidance for chronotherapeutic intervention in CAG management. Through innovative integration of modern chronobiology and traditional temporal medicine principles, the study illuminates the central role of the circadian clock gene in the CAG "inflammation to cancer" transformation and emphasizes the potential of the circadian clock and chronotherapy in reversing the "inflammation to cancer" transformation, offering both mechanistic insights and clinically actionable strategies for CAG treatment via chronobiology.

This study aims to investigate the effects of emodin on proliferation, migration, epithelial-mesenchymal transition(EMT), and autophagy in HONE-1 and CNE-2 cells of nasopharyngeal carcinoma(NPC). HONE-1 and CNE-2 cells were cultured in vitro and divided into control group, low-(7.5 μg·mL~(-1)), and high-(10 μg·mL~(-1)) dose group of emodin. The cells were treated with emodin of different concentrations for 48 h. CCK-8 and EdU experiments detected the proliferation ability of HONE-1 and CNE-2 cells, and clony formation assay detected the clony formation ability of HONE-1 and CNE-2 cells. Transwell assay detected the migration ability of HONE-1 and CNE-2 cells. A stem cell pellet experiment detected the dryness of HONE-1 and CNE-2 cells. Immunofluorescence staining analyzed the expression level of microtubule-associated protein 1 light chain 3β(LC3B) in HONE-1 and CNE-2 cells, and Western blot detected the expression levels of EMT-related proteins and autophagy-related proteins in HONE-1 and CNE-2 cells. The results showed that the IC_(50) of HONE-1 and CNE-2 cells treated with emodin for 48 h were 10.0 and 9.4 μg·mL~(-1), respectively. Compared with the control group, emodin could increase the cell proliferation inhibition rate of HONE-1 and CNE-2 cells, and the effect increased with time or drug dose. Emodin could inhibit the clony formation, migration, and stem cell pelletizing ability of HONE-1 and CNE-2 cells. Emodin could increase the expression level of LC3B in HONE-1 and CNE-2 cells and improve autophagy activity. Compared with the control group, the experimental group exhibited elevated expression levels of EMT-associated protein E-cadherin, reduced expression level of vimentin, increased expression levels of autophagy-related protein 5(ATG5) and LC3B, and decreased expression level of sequestosome 1(p62). In conclusion, emodin can promote the autophagy of human nasopharyngeal carcinoma cells and inhibit the proliferation, cloning, EMT, and pelletizing ability of tumor stem cells.

Ganoderma lucidum spore polysaccharides(GLSP) are the main active ingredients of G. lucidum spores and have pharmacological effects of regulating immunity and inhibiting tumor growth. Cancer-related fatigue is a common concomitant symptom in cancer patients, with no safe and effective therapy. This study established a mouse model of cancer-related fatigue with spleen deficiency syndrome to investigate the effect and mechanism of GLSP in alleviating cancer-related fatigue. First, GLSP was obtained by water extraction and alcohol precipitation, and its content was measured to be approximately 75% by the anthrone sulfate method. GLSP was found to be composed of 10 monosaccharides including glucose, galactose, and mannose by 1-phenyl-3-methyl-5-pyrazolone(PMP) derivatization-HPLC. Using a mouse model of cancer-related fatigue due to spleen deficiency, this study showed that GLSP significantly reduced the tumor volume and weight, prolonged the running time, increased the motilin and gastrin content in the antral tissue, and improved the gastrointestinal digestive function in mice. Moreover, GLSP lowered the serum lactic acid level, increased the ATP concentration in the skeletal muscle, raised the levels of mitochondrial respiratory enzymes Ⅰ and Ⅳ, and promoted material and energy metabolism in the body. In addition, GLSP significantly alleviated the abnormal spleen tissue structure, promoted tumor tissue necrosis, lowered the serum levels of inflammatory factors [interleukin(IL)-1β, tumor necrosis factor(TNF)-α)], increased CD4~+ expression in the spleen tissue, reduced CD8~+ expression, and down-regulated the protein and mRNA levels of JAK2/STAT3 pathway-related factors in model mice. To sum up, GLSP can inhibit Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) activation by reducing IL-6 expression, raise the CD4~+/CD8~+ level, regulate the tumor microenvironment, enhance immunity, improve gastrointestinal absorption and digestion, promote energy metabolism, and increase the skeletal muscle energy storage level, thereby relieving cancer-related fatigue in mice with the spleen deficiency syndrome.

Based on proteomic approaches, this study investigated the anti-breast cancer targets and mechanisms of ergosterol peroxide. The MTT assay was used to evaluate the effect of ergosterol peroxide on the viability of MCF-7 breast cancer cells. Flow cytometry was employed to assess the effects of ergosterol peroxide on apoptosis, mitochondrial membrane potential, reactive oxygen species(ROS), and cell cycle progression in MCF-7 cells. Tandem mass spectrometry-based proteomic analysis was used to determine the subcellular localization and differentially expressed proteins(DEPs) in MCF-7 cells following ergosterol peroxide treatment. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed using the EggNOG and KAAS databases. A protein-protein interaction(PPI) network was constructed via the STRING database. Western blot was conducted to detect the expression levels of relevant proteins. Molecular docking was used to verify the binding affinity of ergosterol peroxide to core target proteins. MTT assay results showed that ergosterol peroxide significantly inhibited MCF-7 cell viability in a time-and concentration-dependent manner. Flow cytometry analysis revealed that treatment with 10, 20, 40 μmol·L~(-1) ergosterol peroxide for 48 hours significantly increased the total apoptosis rate of MCF-7 cells, markedly increased mitochondrial membrane potential, significantly elevated ROS levels, and caused cell cycle arrest at the G_0/G_1 phase. Proteomic analysis identified a total of 385 DEPs between the ergosterol peroxide-treated and control groups, including 64 upregulated and 321 downregulated proteins. Bioinformatics pathway enrichment analysis indicated significant enrichment of the transforming growth factor-β(TGF-β), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and tumor protein p53(p53) signaling pathways among the DEPs, suggesting that ergosterol peroxide may mediate cell cycle arrest and proliferation inhibition through multiple pathways. Western blot results demonstrated increased expression levels of phosphorylated(p)-p53, cytochrome C(CytC), B-cell lymphoma2(Bcl-2)-associated X protein(Bax), and cleaved cysteine-aspartic protease-7(cleaved caspase-7), and decreased expression levels of TGF-β, p-Smad2, p-Smad3, p-PI3K, p-Akt, Bcl-2, cyclin D1(CCND1), and cyclin-dependent kinase 4(CDK4) in MCF-7 cells after ergosterol peroxide treatment. These findings indicate that ergosterol peroxide may inhibit the proliferation and induce apoptosis of MCF-7 breast cancer cells by regulating the TGF-β, PI3K/Akt, and p53 signaling pathways.

This study aims to investigate whether Guiqi Yiyuan Ointment can increase the sensitivity of Lewis lung cancer mice to cisplatin by reducing M2 macrophage polarization and decipher the possible mechanism. Ten SD rats were allocated into a Guiqi Yiyuan Ointment(1.2 g·kg~(-1)·d~(-1)) group and a blank group(an equal volume of normal saline). After continuous gavage for 7 days, the drug-containing serum was prepared. The cell counting kit-8(CCK-8) method was used to screen the optimal intervention concentration of 10% blank serum and 10% drug-containing serum. The cells were allocated into M0, M2(20 ng·mL~(-1) IL-4), M2+blank serum(20 ng·mL~(-1 )IL-4+blank serum), and M2+drug-containing serum(20 ng·mL~(-1) IL-4+drug-containing serum) groups and cultured for 48 h. The proportion of CD206~+ cells in each group was detected by flow cytometry. q-PCR was used to determine the mRNA levels of Janus kinase 3(JAK3), signal transducer and activator of transcription 6(STAT6), and arginase-1(Arg-1) in each group. Enzyme-linked immunosorbent assay(ELISA) was employed to assess the secretion levels of vascular endothelial growth factor(VEGF) and interleukin-10(IL-10) in each group. The cells were then cultured in fresh culture medium for 48 h, and the supernatant after centrifugation was collected as the conditioned medium. Lewis cells were treated with different groups of conditioned media and different concentrations of cisplatin(0-160 μmol·L~(-1)) for 24 h and the cell viability was examined by the CCK-8 method. Fifty SP-grade male C57BL/6 mice were modeled for Lewis lung cancer and then grouped as follows: model, cisplatin [0.005 g·kg~(-1)·(2 d)~(-1)], and cisplatin+low-, medium-, and high-dose Guiqi Yiyuan Ointment [0.005 g·kg~(-1)·(2 d)~(-1) cisplatin+1.6, 3.3, 6.6 g·kg~(-1)·d~(-1) Guiqi Yiyuan Ointment]. After continuous administration for 14 days, the mice were euthanized, and the tumor-bearing tissue was collected. The pathological changes of the tumor-bearing tissue were observed by hematoxylin-eosin staining. Immunofluorescence was used to detect CD206/CD68 ratio changes in the tumor-bearing tissue. Western blot was employed to measure the phosphorylation levels of JAK3 and STAT6 in the tumor-bearing tissue, as well as the expression of B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X protein(Bax). ELISA was employed to measure the VEGF and IL-10 levels in the tumor-bearing tissue. The results of cell experiments showed that compared with the M2 group, the M2+drug-containing serum group showed decreased CD206~+ cells, down-regulated mRNA levels of JAK3, STAT6, and Arg-1, declined VEGF and IL-10 secretion levels, and weakened cell viability. In the animal experiments, compared with the model group and cisplatin group, the combined group showed increased apoptosis and necrotic areas, decreased CD206/CD68 ratio, down-regulated JAK3 and STAT6 phosphorylation levels and Bcl-2 expression level, up-regulated Bax expression level, and lowered VEGF and IL-10 secretion levels. In conclusion, Guiqi Yiyuan Ointment may increase the sensitivity of Lewis lung cancer mice to cisplatin by inhibiting the JAK3/STAT6 pathway and reducing the polarization of M2 macrophages.

Gastrointestinal malignant tumors are a group of severely life-threatening tumors. Their incidence and mortality rates consistently rank among the top 10 cancers worldwide and are increasing year by year. Based on his long-term clinical practice, Professor Zhou Zhongying proposes the theory of "cancer toxin". The research team led by Professor CHENG Hai-bo further establishes the pathogenesis theory of cancer toxin, holding that cancer toxin is the key factor in the occurrence and development of tumors, and thus taking "anti-cancer and detoxification" as the basic therapeutic principle. With the vigorous promotion of TCM, various active ingredients of TCM are extracted and make a difference in tumor therapy. These active ingredients can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an active ingredient extracted from the skin of Bufo gargarizans with detoxifying, anti-swelling, and pain-relieving effects and is widely used in the treatment of intermediate and advanced tumors. Clinical studies have revealed that cinobufotalin enhances tumor control rates, prolongs survival time, improves quality of life, and reduces the incidence of adverse reactions when combined with chemotherapy, radiotherapy, or targeted therapies. The mechanism studies have demonstrated that cinobufotalin plays a therapeutic role by inhibiting cell proliferation and invasion, inducing tumor cell apoptosis, modulating immune response, reversing drug resistance, etc. This paper reviews the research progress on cinobufotalin from the perspective of pathogenesis theory of cancer toxin through summarizing domestic and international reported research on clinical application and mechanism of cinobufotalin against gastrointestinal malignant tumors in recent years. The findings aim to provide a theoretical basis for research on the anti-tumor effect of cinobufotalin and a reference for standardized use and in-depth research of drugs.

Colorectal cancer(CRC), a prevalent malignancy of the digestive system, exhibits an escalating incidence and mortality rate in China. While contemporary western therapeutic approaches demonstrate efficacy in tumor suppression and symptom management, their clinical benefits are substantially limited by adverse effects, drug resistance, and high recurrence rates. Consequently, developing novel therapeutic strategies with enhanced efficacy and safety profiles has emerged as a critical research priority in oncology. TGF-β signaling pathway plays a pivotal role in modulating CRC cell proliferation, differentiation, and apoptosis, and it is intimately involved in tumorigenesis, progression, and metastasis, thereby representing a promising molecular target for CRC treatment. Traditional Chinese medicine(TCM) exhibits distinctive therapeutic advantages in CRC management through its multi-target, multi-pathway regulatory mechanisms. Notably, TCM has demonstrated significant efficacy in preventing postoperative recurrence and metastasis, mitigating treatment-related side effects, and improving patients' quality of life, establishing its integral role in comprehensive CRC therapy. Current evidence indicates that various TCM active constituents, including polyphenols, terpenoids, alkaloids, polysaccharides, flavonoids, and isothiocyanates, as well as compound formulas such as Jianpi Tongluo Formula, Jianpi Xiao'ai Formula, modified Shenling Baizhu Decoction, Qingjie Fuzheng Granules, and Chanling Ointment, can effectively modulate the TGF-β signaling pathway and its interactive networks. These therapeutic agents exert anti-CRC effects through diverse mechanisms, including apoptosis induction, EMT inhibition, macrophage polarization, stemness attenuation, immune activation, chemoresistance reversal, and cell cycle arrest. This review systematically synthesizes contemporary research advances in TCM interventions for CRC, with a particular emphasis on the mechanism underpinning TGF-β pathway modulation. Our findings provide valuable insights for the development of innovative anti-CRC agents and the optimization of clinical therapeutic regimens.

Malignant tumors, as a major public health issue facing the world, have extremely complex pathogenesis. Molecular biology features represented by acidic microenvironment and lipid metabolism disorders are closely related to tumor invasion and metastasis. Traditional Chinese medicine(TCM) holds that the diseases caused by phlegm toxicity are characterized by heaviness, turbidity, stickiness, and difficulty in resolving. Modern pharmacological research has confirmed that as a TCM for resolving phlegm and detoxifying to treat phlegm toxicity, it can not only exert anti-cancer effects by directly inhibiting tumor cell proliferation but also reshape the steady-state regulatory network of the tumor microenvironment, including downregulating the microenvironment of lactate accumulation mediated by hypoxia-inducible factor 1α(HIF-1α) and regulating fatty acid synthase(FASN)-related lipid metabolism reprogramming processes, thereby antagonizing tumor invasion and metastasis. The innovative TCM theory of cancer toxicity pathogenesis proposed by our team suggests that the pathogenic characteristics of phlegm toxicity are homologous to the pathological accumulation of abnormal metabolites in the tumor microenvironment. This study systematically reviews the relevant literature on the treatment of tumors with TCM for resolving phlegm and detoxifying, deeply analyzes the theoretical basis of TCM, summarizes the clinical experience of famous TCM practitioners, and explores the clinical efficacy of TCM for resolving phlegm and detoxifying against tumors. At the same time, this study objectively summarizes its active ingredients and anti-tumor mechanisms, so as to provide reference for the prevention and treatment of malignant tumors with TCM.

Network pharmacology and cell experiments were employed to explore the treatment mechanism of Blaps rynchopetera for lung adenocarcinoma(LUAD). The targets of the blood-absorbed components of B. rynchopetera and LUAD were retrieved, and the common targets shared were subjected to gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses to predict the functional processes and main active substances of B. rynchopetera in treating LUAD. Molecular docking was performed on the core active compounds among the blood-absorbed components and key targets. Furthermore, CCK-8 assay, colony formation assay, acridine orange staining, flow cytometry, and Western blot were employed to decipher the mechanism of B. rynchopetera in treating LUAD. The 39 blood-absorbed components of B. rynchopetera were associated with 766 targets. The 334 common targets shared by the blood-absorbed components and LUAD(2 820 targets) were selected as potential therapeutic targets. GO and KEGG enrichment analyses indicated that the mitogen-activated protein kinase(MAPK) signaling pathway was closely related to LUAD. The main active substances among the blood-absorbed components included kaempferol, licochalcone B,(3,6,9-trimethylidene-2-oxo-3a, 4,5,6a, 7,8,9a, 9b-octahydroazuleno\[4,5-b\]furan-8-yl) acetate, myricetin, and naringenin chalcone. The cell experiments demonstrated that B. rynchopetera reduced the viability of LUAD cells in a concentration-dependent manner. By downregulating the expression of proliferating cell nuclear antigen(PCNA) and upregulating the expression of B-cell lymphoma-2(Bcl-2)-associated X protein(Bax)/Bcl-2, cysteine-aspartate specific protease 3(caspase-3), Beclin1, and microtubule-associated protein light chain 3B-Ⅱ(LC3B-Ⅱ), B. rynchopetera induced apoptosis and autophagy, thereby inhibiting the proliferation of LUAD cells. The autophagy inhibitor chloroquine enhanced the pro-apoptotic effect of B. rynchopetera. Additionally, the c-Jun N-terminal kinase(JNK) inhibitor(SP600125) suppressed the activation of the JNK pathway as well as B. rynchopetera-induced apoptosis and autophagy. In conclusion, B. rynchopetera activates the MAPK/JNK pathway to induce apoptosis and autophagy, thereby exerting the therapeutic effect on LUAD.

To investigate the role of Fuzi polysaccharide(FPS) in combination with lenvatinib(LEN) in regulating tumor-associated macrophage(TAM) polarization to enhance the anti-hepatocellular carcinoma(HCC) efficacy, the non-toxic concentrations of FPS and LEN on RAW264.7 cells were screened by cell counting kit-8(CCK-8). The co-culture system of RAW264.7 and Hepa1-6 cells was established, and flow cytometry was used to detect changes in M1 and M2 macrophage phenotypes. Quantitative real-time polymerase chain reaction(qRT-PCR) was performed to assess the mRNA expression levels of M1-associated factors, inducible nitric oxide synthase(iNos) and interleukin 12b(IL-12b), as well as M2-associated factors arginase 1(Arg-1) and IL-10. The effects of macrophages treated with FPS and LEN on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by 5-ethynyl-2'-deoxyuridine(EdU) staining, wound healing assay, Transwell invasion assay, and Annexin V/PI double-staining flow cytometry. A C57BL/6 subcutaneous HCC xenograft mouse model was established to observe the tumor growth, body weight, spleen index, and tumor-infiltrating macrophage polarization. CCK-8 assay showed that 50-200 mg·L~(-1) FPS and 1-5 μmol·L~(-1) LEN had no inhibitory effects on RAW264.7 macrophages. Flow cytometry and qRT-PCR results demonstrated that 200 mg·L~(-1) FPS + LEN significantly increased the proportion of M1 macrophages(P<0.01) and the M1/M2 ratio(P<0.01), upregulated the expressions of M1-associated genes iNos and IL-12b(P<0.01), reduced the proportion of M2 macrophages(P<0.01), and inhibited the expressions of M2-associated genes Arg-1 and IL-10(P<0.01). Functional assays revealed that macrophages of the FPS + LEN group inhibited Hepa1-6 proliferation(P<0.01), promoted apoptosis(P<0.01), and reduced migration and invasion(P<0.01). In vivo experiments showed that compared to those of the LEN group, the tumor volume was significantly reduced(P<0.05), and the spleen index was significantly increased(P<0.05) in the FPS + LEN group. The body weight was not decreased, and the proportion of M1 macrophages and the M1/M2 ratio in the tumors were significantly increased in the FPS + LEN group(P<0.01). In conclusion, FPS combined with LEN enhances the anti-HCC effect by promoting the M1 polarization of TAMs.