The interactions between traditional Chinese medicine and gut microbiota in cancers: Current status and future perspectives.

The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies.

Different effects of selenium speciation on selenium absorption, selenium transformation and cadmium antagonism in garlic.

Currently, planting selenium-rich crops using inorganic selenium such as selenate and selenite is used to address human selenium deficiency problems. In this paper, besides the above two traditional inorganic selenium speciation, we chose a new organic selenium speciation of potassium selenocyanoacetate to investigate the different effects of selenium speciation on selenium absorption, selenium transformation and cadmium antagonism via foliar application. Plantingexperiments showed that the selenium content of garlic bulbs treated with organic selenium was 1.8-3.9 times higher than that of inorganic selenium. Additionally, the absorption and transformation efficiency of organic selenium in garlic was also the highest, reaching over 95 %. Importantly, it was noteworthy that the cadmium content in bulbs treated with organic selenium was significantly lower than the Chinese food safety standard (0.2 mg/kg). Hence, this study provides an efficient organic selenium speciation which is beneficial to meet human selenium requirements and ensure safe utilization of cadmium-contaminated soils.

Interfering with the AKT/mTOR/STAT3/ID1 signaling axis with usenamine A restrains the proliferative and invasive potential of human hepatocellular carcinoma cells.

BACKGROUND: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. METHODS: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. RESULTS: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin-proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. CONCLUSION: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin-proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression.

A review on the research progress of traditional Chinese medicine with anti-cancer effect targeting ferroptosis.

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM.

The Role of Traditional Chinese Medicine in Cancer Immunotherapy: Current Status and Future Directions.

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor-[Formula: see text], and IFN-[Formula: see text], as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor-[Formula: see text], and tumor necrosis factor-[Formula: see text]. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors.

DHMMF, a natural flavonoid from Resina Draconis, inhibits hepatocellular carcinoma progression via inducing apoptosis and G2/M phase arrest mediated by DNA damage-driven upregulation of p21.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is extremely malignant in nature. It is an important way to discover anti-cancer drugs from natural products at present. (R)-7,3'-dihydroxy-4'-methoxy-8-methylflavane (DHMMF), a natural flavonoid, was isolated from Resina Draconis which is the red resin from Dracaena cochinchinensis (Lour.) S. C. Chen. However, the anti-hepatoma effect and underlying mechanisms of DHMMF remain unclear. Herein, we demonstrated that DHMMF treatment significantly inhibited the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. The IC50 value of DHMMF for HepG2 and SK-HEP-1 cells were 0.67 µM and 0.66 µM, respectively, while the IC50 value of DHMMF for human normal liver LO2 cells was 120.60 µM. DHMMF induced DNA damage, apoptosis, and G2/M phase arrest in HepG2 and SK-HEP-1 cells. Furthermore, the anti-proliferative and pro-apoptotic effects of DHMMF in human hepatoma cells were mediated by the upregulation of p21. Importantly, DHMMF exhibited potent anti-HCC efficacy in a xenograft mice model and an orthotopic mice model of liver cancer. Additionally, the combined administration of DHMMF and polo-like kinase 1 (PLK1) inhibitor BI 6727 showed a synergistic anti-HCC efficacy. Collectively, we demonstrated that DHMMF treatment induced apoptosis and G2/M phase arrest via DNA damage-driven upregulation of p21 expression in human hepatoma cells. DHMMF may serve as a promising drug candidate for HCC treatment, especially for patients of HCC with low p21 expression. Our results also suggested that DHMMF treatment in combination with PLK1 inhibitor may serve as a potential treatment strategy for patients with HCC.

Tripartite motif-containing protein 31 confers protection against nonalcoholic steatohepatitis by deactivating mitogen-activated protein kinase kinase kinase 7.

BACKGROUND AIMS: As a global health threat, NASH has been confirmed to be a chronic progressive liver disease that is strongly associated with obesity. However, no approved drugs or efficient therapeutic strategies are valid, mainly because its complicated pathological processes is underestimated. APPROACH RESULTS: We identified the RING-type E3 ubiquitin transferase-tripartite motif-containing protein 31 (TRIM31), a member of the E3 ubiquitin ligases family, as an efficient endogenous inhibitor of transforming growth factor-beta-activated kinase 1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7), and we further confirmed that TRIM31 is an MAP3K7-interacting protein and promotes MAP3K7 degradation by enhancing ubiquitination of K48 linkage in hepatocytes. Hepatocyte-specific Trim31 deletion blocks hepatic metabolism homeostasis, concomitant with glucose metabolic syndrome, lipid accumulation, up-regulated inflammation, and dramatically facilitates NASH progression. Inversely, transgenic overexpression, lentivirus, or adeno-associated virus-mediated Trim31 gene therapy restrain NASH in three dietary mice models. Mechanistically, in response to metabolic insults, TRIM31 interacts with MAP3K7 and conjugates K48-linked ubiquitination chains to promote MAP3K7 degradation, thus blocking MAP3K7 abundance and its downstream signaling cascade activation in hepatocytes. CONCLUSIONS: TRIM31 may serve as a promising therapeutic target for NASH treatment and associated metabolic disorders.

Chinese dragon's blood ethyl acetate extract suppresses gastric cancer progression through induction of apoptosis and autophagy mediated by activation of MAPK and downregulation of the mTOR-Beclin1 signalling cascade.

Gastric cancer (GC) is a malignancy with high morbidity and mortality. Chinese dragon's blood is a traditional Chinese medicine derived from the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen. However, the antigastric cancer effect of Chinese dragon's blood has not yet been reported. Herein, we demonstrated that Chinese dragon's blood ethyl acetate extract (CDBEE) suppressed the proliferative and metastatic potential of human gastric cancer MGC-803 and HGC-27 cells. CDBEE suppressed epithelial-mesenchymal transition in MGC-803 and HGC-27 cells. Moreover, CDBEE induced apoptotic and autophagic cell death in MGC-803 and HGC-27 cells. The cytotoxicity of CDBEE in human gastric epithelial GES-1 cells was dramatically weaker than that in human gastric cancer cells. Mechanistically, the activation of the mitogen-activated protein kinase (MAPK) signalling pathway was involved in the growth inhibition of MGC-803 and HGC-27 cells by CDBEE. Additionally, CDBEE-induced autophagic cell death was mediated by downregulation of the mammalian target of rapamycin (mTOR)-Beclin1 signalling cascade and upregulation of the ATG3/ATG7-LC3 signalling cascade. Importantly, CDBEE exhibited potent anti-GC efficacy in vivo without obvious toxicity or side effects. Therefore, CDBEE may be a promising candidate drug for the treatment of gastric cancer, especially for GC patients with aberrant MAPK signalling or mTOR signalling.

Microglial exosomal miR-466i-5p induces brain injury via promoting hippocampal neuron apoptosis in heatstroke.

Background: Brain injury is the main cause of poor prognosis in heatstroke (HS) patients due to heat-stress-induced neuronal apoptosis. However, as a new cross-talk way among cells, whether microglial exosomal-microRNAs (miRNAs) are involved in HS-induced neuron apoptosis has not been elucidated. Methods: We established a heatstroke mouse model and a heat-stressed neuronal cellular model on HT22 cell line. Then, we detected neuron apoptosis by histopathology and flow cytometry. The microglial exosomes are isolated by standard differential ultracentrifugation and characterized. Recipient neurons are treated with the control and HS exosomes, whereas in vivo, the exosomes were injected into the mice tail vein. The internalization of HS microglial exosomes by neurons was tracked. Apoptosis of HT22 was evaluated by flow cytometry and Western blot in vitro, TUNEL assay, and immunohistochemistry in vivo. We screened miR-466i-5p as the mostly upregulated microRNAs in HS exosomes by high-throughput sequencing and further conducted gene ontology (GO) pathway analysis. The effect and mechanism of HS exosomal miR-466i-5p on the induction of neuron apoptosis are demonstrated by nasal delivery of miR-466i-5p antagomir in vivo and transfecting miR-466i-5p mimics to HT22 in vitro. Results: HS induced an increase in neurons apoptosis. Microglial exosomes are identified and taken up by neurons, which induced HT22 apoptosis in vivo and vitro. HS significantly changed the miRNA profiles of microglial exosomes based on high-throughput sequencing. We selected miR-466i-5p as a target, and upregulated miR-466i-5p induced neurons apoptosis in vivo and vitro experiments. The effects are exerted by targeting Bcl-2, activating caspase-3 to induce neurons apoptosis. Conclusions: We demonstrate the effect of microglial exosomal miR-466i-5p on neurons apoptosis and reveal potentially Bcl-2/caspase-3 pathway in heatstroke.

Study of New Mini-Channel Trans-Critical CO2 Heat Pump Gas Cooler.

A gas cooler is one of the important parts of a carbon dioxide (CO2) heat pump water heater, and it must meet the needs of not only pressurization but also heat transfer. It is important to study gas coolers. In this paper, a heat exchanger with a spiral channel is studied. ANSYS CFX software was used to analyze the flow and heat transfer characteristics of the heat exchanger (single-plate model). The influences of the cooling pressure of CO2, the mass flux of CO2, the mass flux of water and the channel radius of CO2 are discussed. In this paper, the results show that the cooling pressure of CO2, the mass flux of CO2 and the channel radius of CO2 all have a large influence on the local heat transfer coefficient: with an increase in the cooling pressure of CO2, the peak value of the heat transfer coefficient of CO2 decreases and the average heat transfer coefficient decreases; with an increase in the mass flux of CO2, the peak value of the heat transfer coefficient of CO2 increases and the average heat transfer coefficient increases; and with a decrease in the channel radius of CO2, the peak value of the heat transfer coefficient of CO2 increases. The water mass flux has only a slight effect on heat transfer, and the lower cooling pressure of CO2 corresponds to a higher peak heat transfer coefficient, which can reach 27.5 kW∙m-2∙K-1 at 9 MPa.

[Anti-tumor effect of Huaier extract supernatant on human gastric cancer HGC-27 and MGC-803 cells].

The purpose of this study was to investigate the effect of Huaier extract supernatant(HES) on the proliferation, apoptosis, autophagy, and migration of human gastric cancer HGC-27 and MGC-803 cells and its molecular mechanisms. The main components in HES were preliminarily analyzed by high-performance liquid chromatography-mass spectrometry(HPLC-MS). Methyl thiazolyl tetrazolium(MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine(EdU) staining assay were used to explore the effect of HES on the proliferation of human gastric cancer HGC-27 and MGC-803 cells. Hoechst staining and flow cytometry assay were used to determine the effect of HES on apoptosis of human gastric cancer HGC-27 and MGC-803 cells. Acridine orange staining and cell scratch assay were used to determine the effect of HES on autophagy and migration of human gastric cancer HGC-27 and MGC-803 cells, respectively. Western blot was used to investigate the regulatory effect of HES on the expression levels of proteins related to apoptosis, epithelial-mesenchymal transition(EMT), and signaling pathways in human gastric cancer HGC-27 and MGC-803 cells. The results showed that HES mainly contained some components with high polarities. HES significantly reduced the cell viability of human gastric cancer cells in a dose-and time-dependent manner. The IC_(50 )values after 48 h of HES treatment in human gastric cancer HGC-27 and MGC-803 cells were 7.56 and 10.77 g·L~(-1), respectively. Meanwhile, HES inhibited the colony-forming ability and short-term proliferation of human gastric cancer cells. The apoptosis rates of HGC-27 and MGC-803 cells treated with 8 g·L~(-1) HES for 72 h were 62.13%±8.92% and 54.50%±3.26%, respectively. HES also promoted autophagy in human gastric cancer cells and impaired their migration ability in vitro. Moreover, HES up-regulated the cleavage of the apoptosis marker poly ADP-ribose polymerase(PARP) and the protein expression level of the epithelial cell marker E-cadherin, and down-regulated the protein levels of phosphorylated-mammalian target of rapamycin(p-mTOR), phosphorylated-S6(p-S6), and phosphorylated-extracellular signal-regulated kinase(p-ERK) in human gastric cancer cells. Therefore, HES is one of the effective anti-tumor components of Huaier, which inhibits the proliferation and migration of human gastric cancer cells, and induces apoptosis and autophagy. Moreover, the mTOR signal and ERK signal may be involved in the anti-gastric cancer effect of HES. This study provides novel references for the in-depth research and clinical application of Huaier. It is also of great significance to promote the scientific development and utilization of Huaier.

Heparin-induced thrombocytopenia in Chinese patients: 240 patients study in one center.

BACKGROUND: The study was conducted in order to analyze the incidence of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) in 240 patients from the Department of Vascular Surgery in China, to evaluate the current laboratory detection technique, and to explore the feasibility for the technique to be developed in China. METHODS: 240 patients receiving unfractionated heparin (UFH) were studied in one center. Before and after the UFH treatment, platelet count, HIT-antibody ELISA test, and heparin-induced platelet aggregation (HIPA) were tested. RESULTS: Among 240 patients, HIT was diagnosed in 36 cases. The incidence was 15%. HITTS occurred in 6 cases (2.5%). The median time of thrombocytopenia was the 8th day. Platelet counts recovered to normal level in 3 - 6 days after heparin withdrawal CONCLUSIONS: The incidence of HIT is higher; however, the incidence of HITTS is lower. Monitoring platelet count, which is simple and easy to do and available in hospitals at different levels (township hospital included), is a reliable method to diagnose HIT early. The HIT-antibody ELISA test could be introduced in specific hospitals to prescreen HIT. In view of the higher sensitivity and specificity of HIPA, it can be used in larger diagnostic centers in all the big cities of China.