OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

OBJECTIVE: To investigate the application value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in etiological diagnosis of children with hematological malignancies complicated with pneumonia. METHODS: We retrospectively analyzed the clinical data of children with hematological malignancies who underwent BALF mNGS pathogenic detection due to pneumonia. All patients underwent mNGS detection of bronchoalveolar lavage fluid as well as traditional methods(including sputum culture, bronchoalveolar lavage fluid culture, blood culture, serological detection of pathogens, etc.). By analyzing the results of mNGS and traditional methods, we compared key indicators such as the positive rate, etiological distribution. RESULTS: A total of 26 children with hematological malignancies enrolled in the study, including 12 males and 14 females, with a median age of 4.9 (1.8-14.9) years, underwent bronchoalveolar lavage (BAL) 35 times. A total of 17 pathogenic microorganisms were detected in BALF mNGS, including 9 cases of bacterial infection, 10 cases of viral infection, 3 cases of fungal infection, 2 cases of mycoplasma infection and 8 cases of mixed infection, and the most commonly detected bacteria, viruses and fungi were streptococcus pneumoniae, cytomegalovirus and pneumocystis jirovecii, respectively. The positive rate of mNGS detection (91.43%) was significantly higher than that of traditional methods detection (20%, P <0.001). A total of 25 cases were adjusted according to BALF mNGS results. CONCLUSION The application of BALF mNGS technology can improve the detection rate of the pathogens in children with hematological malignancies complicated with pneumonia, initially revealed the pathogen spectrum of pulmonary infection in this group, and effectively guide clinical medication, improve treatment outcomes.
Humans ; Bronchoalveolar Lavage Fluid/microbiology* ; Hematologic Neoplasms/complications* ; Child ; Child, Preschool ; Infant ; Retrospective Studies ; Male ; Female ; Adolescent ; High-Throughput Nucleotide Sequencing ; Pneumonia/microbiology*

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

The field of onco-microbiome is rapidly expanding. Multiple studies have shown the crucial role of gut microbiota in the regulation of nutrient metabolism, immunomodulation and protection against pathogens. Tools for manipulating the gut microbiota include dietary modification and faecal microbiota transfer. Accumulating evidence has also documented the application of specific intestinal microbiome in cancer immunotherapy, notably in enhancing the efficacy of immune checkpoint inhibitors. The aim of this review is to focus on the East Asian microbiome and to provide a current overview of microbiome science and its clinical application in cancer biology and immunotherapy.
Humans ; Gastrointestinal Microbiome ; Neoplasms/microbiology* ; Immunotherapy/methods* ; Asia, Eastern ; Medical Oncology ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use* ; East Asian People

OBJECTIVE: To observe the effects of thumbtack-needle embedding therapy of auricular acupuncture on gastrointestinal function and intestinal microflora in the patients with gastric cancer after operation, and to explore its mechanism. METHODS: A total of 80 patients with gastric cancer after radical operation were randomly divided into an observation group (40 cases, 3 cases discontinued) and a control group (40 cases, 3 cases discontinued). The patients of both groups received the perioperative care for accelerating recovery. Additionally, in the observation group, the thumbtack-needle embedding therapy of auricular acupuncture was delivered at the auricular points of unilateral side, including Wei (CO₄), Pi (CO₁₃), Dachang (CO₇), Xiaochang (CO₆), Yuanzhong (AT_2,3,4i), Erzhong (HX₁), Sanjiao (CO₁₇) and Jiaowozhong (TF₃), and the needles were embedded and retained for 72 h. The postoperative recovery time of gastrointestinal function (the postoperative bowel sound recovery time, the first exhaust time, the first defecation time), the postoperative hospital stay and pain visual analogue scale (VAS) score were observed in the two groups. Before operation and on day 5 after operation, the serum gastrin level was detected in the two groups. The third-generation 16S rRNA sequencing technology was used to detect the composition and relative abundance of intestinal flora in the two groups before and after operation. RESULTS: Compared with the control group, the postoperative bowel sound recovery time, the first exhaust time and the first defecation time were shortened in the observation group (P<0.05). In the observation group, the VAS scores at 24 h, 48 h, and 72 h after surgery were lower than those of the control group, respectively (P<0.05). There was no significant differences in postoperative hospital stay and serum gastrin level between the two groups (P>0.05). The alpha diversity analysis showed that the differences in Shannon index, Simpson index, Pielou_J index and Pd_fath index were not significant statistically after intervention between the two groups (P>0.05). After intervention, the community structure of the fecal sample was similar at each taxonomic level between the two groups, and although the proportion between species was various, the difference was not significant (P>0.05). After intervention, there were 55 species with the differences between the two groups, 17 species of them presented significant difference in relative abundance in the observation group and 38 species in the control group. Regarding the level of genus, the levels of Klebsiell and Enterobacter increased (P<0.05) and the level of Streptococcus decreased (P<0.05) in the observation group. The main microbial groups that played an important role were Coprobacillaceae, Sutterellaceae and Yersiniaceae in the observation group. KEGG function prediction indicated that the function of intestinal microflora was mainly associated with the cofactor and vitamin metabolism, carbohydrate metabolism, and amino acid metabolism. CONCLUSION The thumbtack-needle embedding therapy of auricular acupuncture improves the postoperative gastrointestinal function of the patients with gastric cancer probably through regulating the structure and relative abundance of intestinal microflora and affecting the energy metabolism.
Humans ; Male ; Female ; Middle Aged ; Acupuncture, Ear/instrumentation* ; Gastrointestinal Microbiome ; Aged ; Stomach Neoplasms/therapy* ; Adult ; Acupuncture Points ; Gastrointestinal Tract/microbiology* ; Intestines/physiopathology* ; Postoperative Period ; Acupuncture Therapy

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, highlighting the urgent need for novel preventive and therapeutic strategies. Emerging research highlights the crucial role of the gut microbiota, including bacteria, fungi, viruses, and their metabolites, in the pathogenesis of CRC. Dysbiosis, characterized by an imbalance in microbial composition, contributes to tumorigenesis through immune modulation, metabolic reprogramming, and genotoxicity. Specific bacterial species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis , along with fungal agents like Candida species, have been implicated in CRC progression. Moreover, viral factors, including Epstein-Barr virus and human cytomegalovirus, are increasingly recognized for their roles in promoting inflammation and immune evasion. This review synthesizes the latest evidence on host-microbiome interactions in CRC, emphasizing microbial metabolites, such as short-chain fatty acids and bile acids, which may act as both risk factors and therapeutic agents. We further discuss the latest advances in microbiota-targeted clinical applications, including biomarker-assisted diagnosis, next-generation probiotics, and microbiome-based interventions. A deeper understanding of the role of gut microbiome in CRC pathogenesis could pave the way for diagnostic, preventive, and personalized therapeutic strategies.
Humans ; Dysbiosis/microbiology* ; Colorectal Neoplasms/metabolism* ; Gastrointestinal Microbiome/physiology* ; Animals

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors.
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Humans ; Lung Neoplasms ; RNA, Ribosomal, 16S/genetics* ; Bacteria/genetics* ; Microbiota ; Respiratory System ; Lung/microbiology*

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.
Female ; Humans ; Vagina/microbiology* ; Uterine Cervical Neoplasms/genetics* ; Uterine Cervical Dysplasia ; Cervix Uteri ; Lactobacillus/genetics* ; Papillomavirus Infections