Targeting lipid reprogramming in the tumor microenvironment by traditional Chinese medicines as a potential cancer treatment.

In the last ten years, there has been a notable rise in the study of metabolic abnormalities in cancer cells. However, compared to glucose or glutamine metabolism, less attention has been paid to the importance of lipid metabolism in tumorigenesis. Recent developments in lipidomics technologies have allowed for detailed analysis of lipid profiles within cancer cells and other cellular players present within the tumor microenvironment (TME). Traditional Chinese medicine (TCM) and its bioactive components have a long history of use in cancer treatments and are also being studied for their potential role in regulating metabolic reprogramming within TME. This review focuses on four core abnormalities altered by lipid reprogramming in cancer cells: de novo synthesis and exogenous uptake of fatty acids (FAs), upregulated fatty acid oxidation (FAO), cholesterol accumulation, which offer benefits for tumor growth and metastasis. The review also discusses how altered lipid metabolism impacts infiltrating immune cell function and phenotype as these interactions between cancer-stromal become more pronounced during tumor progression. Finally, recent literature is highlighted regarding how cancer cells can be metabolically reprogrammed by specific Chinese herbal components with potential therapeutic benefits related to lipid metabolic and signaling pathways.

Case report: A case of high grade serous carcinoma of peritoneal origin.

This case report describes an 80-year-old female patient admitted to the emergency department due to abdominal distension, abdominal pain, and hematemesis persisting for three days. Subsequent postoperative pathological examination confirmed the diagnosis of peritoneal cancer. The occurrence, diagnosis, treatment, and prognosis of primary peritoneal cancer (PPC) are presented in detail. PPC is a type of cancer originating from the primary peritoneal mesothelium organization, causing diffuse malignant tumors in the abdominal and pelvic regions. Due to the lack of specific clinical manifestations for this disease, the importance of early diagnosis and treatment is hereby emphasized. The article also mentions the histological source of this type of cancer and the advantages of preoperative intraperitoneal chemotherapy in improving the efficacy of PPC treatment. Finally, the importance of a comprehensive treatment approach and proficient use of targeted therapy techniques are highlighted to enhance the treatment outcomes of PPC.

The Atlas of the Inferior Mesenteric Artery and Vein under Maximum-Intensity Projection and Three-Dimensional Reconstruction View.

(1) Background: Understanding vascular patterns is crucial for minimizing bleeding and operating time in colorectal surgeries. This study aimed to develop an anatomical atlas of the inferior mesenteric artery (IMA) and vein (IMV). (2) Methods: A total of 521 patients with left-sided colorectal cancer were included. IMA and IMV patterns were identified using maximum-intensity projection (MIP) and three-dimensional (3D) reconstruction techniques. The accuracy of these techniques was assessed by comparing them with surgical videos. We compared the amount of bleeding and operating time for IMA ligation across different IMA types. (3) Results: Most patients (45.7%) were classified as type I IMA, followed by type II (20.7%), type III (22.6%), and type IV (3.5%). Newly identified type V and type VI patterns were found in 6.5% and 1% of patients, respectively. Of the IMVs, 49.9% drained into the superior mesenteric vein (SMV), 38.4% drained into the splenic vein (SPV), 9.4% drained into the SMV-SPV junction, and only 2.3% drained into the first jejunal vein (J1V). Above the root of the left colic artery (LCA), 13.1% of IMVs had no branches, 50.1% had one, 30.1% had two, and 6.7% had three or more branches. Two patients had two main IMV branches, and ten had IMVs at the edge of the mesocolon with small branches. At the IMA root, 37.2% of LCAs overlapped with the IMV, with 34.0% being lateral, 16.9% distal, 8.7% medial, and both the marginal type of IMV and the persistent descending mesocolon (PDM) type represented 1.4%. MIP had an accuracy of 98.43%, and 3D reconstruction had an accuracy of 100%. Blood loss and operating time were significantly higher in the complex group compared to the simple group for IMA ligation (p < 0.001). (4) Conclusions: A comprehensive anatomical atlas of the IMA and IMV was provided. Complex IMA patterns were associated with increased bleeding and operating time.

Short-and long-term outcomes of one-stage versus two-stage gastrectomy for perforated gastric cancer: a multicenter retrospective propensity score-matched study.

OBJECTIVE: There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the single-stage and two-stage strategies. METHODS: All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared. RESULTS: Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes [31(27, 38) vs 17 (12, 24), P < 0.001], required less blood transfusion [0 (0, 100) vs 200 (0, 800), P = 0.034], had a shorter ICU stay [0 (0, 1.5) vs 3 (0, 3), P = 0.009], and had a significantly better OS (Median OS: 45 months vs 11 months, P = 0.007). Compared with propensity score-matched regular GC patients without perforation, PGC patients who underwent one-stage gastrectomy had a poorer quality of lymphadenectomy [17 (12, 24) vs 29 (21, 37), P < 0.001] and suffered a worse OS (Median OS: 18 months vs 30 months, P = 0.024). Conversely, two-stage gastrectomy can achieve a comparable quality of lymphadenectomy (P = 0.506) and a similar OS (P = 0.096) compared to propensity score-matched regular GC patients. CONCLUSIONS: For PGC patients in poor condition, two-stage treatment is a better option when D2 radical gastrectomy cannot be achieved in emergency surgery, based on our findings that two-stage gastrectomy could provide PGC patients with a better quality of lymphadenectomy and a better OS.

Synergetic effects and inhibition mechanisms of the polysaccharide-selenium nanoparticle complex in human hepatocarcinoma cell proliferation.

BACKGROUND: Active components from natural fungal products have shown promising potential as anti-tumor therapeutic agents. In the search for anti-tumor agents, research to overcome the drawbacks of high molecular weight and low bioavailability of pure polysaccharides, polysaccharide-conjugated selenium nanoparticles (SeNPs) has attracted much attention. RESULTS: A novel polysaccharide-selenium nanoparticle complex was produced, in which SeNPs were decorated with polysaccharide obtained from fermented mycelia broth of Lactarius deliciosus (FLDP). Transmission electron microscope, dynamic light scattering, and X-ray photoelectron spectroscopy were utilized to characterize the FLDP-SeNPs; and human hepatocarcinoma cell line (HepG2) was used to assess growth inhibition efficacy. The FLDP-SeNPs that were prepared had a spherical shape with the smallest mean diameter of 32 nm. The FLDP-SeNPs showed satisfactory dispersibility and stability after combination, demonstrating that a reliable consolidated structure had formed. The results revealed that FLDP-SeNPs had notable growth inhibition effects on HepG2 cells. They reduced the membrane potential of mitochondria significantly, increased the generation of reactive oxygen species, enhanced levels of both Caspase-3 and Caspase-9, and led to the nucleus in a wrinkled form. CONCLUSION: The FLDP-SeNPs could exert a synergetic toxicity reduction and inhibition enhancement effect on HepG2 cells by inducing early apoptosis, through mitochondria-mediated cytochrome C-Caspases and reactive oxygen species-induced DNA damage pathways. These results indicate that FLDP-SeNP treatment of HepG2 cells induced early apoptosis with synergetic efficacy, showing that FLDP-SeNPs can be useful as natural anti-tumor agents. © 2024 Society of Chemical Industry.

Amelioration of Acute Alcoholic Liver Injury via Attenuating Oxidative Damage and Modulating Inflammation by Means of Ursodeoxycholic Acid-Zein Nanoparticles.

Ursodeoxycholic acid (UDCA) has been broadly adopted for the clinical treatment of hepatic and biliary diseases; however, its poor water-solubility becomes an obstacle in wide applications. To overcome these challenges, herein, a two-tier UDCA-embedded system of zein nanoparticles (NPs) along with a polyelectrolyte complex was designed under facile conditions. Both the UDCA-zein NPs and their inclusion microcapsules showed a spherical shape with a uniform size. A typical wall plus capsule/core structure was formed in which UDCA-zein NPs distributed evenly in the interior. The UDCA inclusion microcapsules had an encapsulation rate of 67% and were released in a non-Fickian or anomalous transport manner. The bioavailability and efficacy of UDCA-zein NPs were assessed in vivo through the alcoholic liver disease (ALD) mouse model via intragastric administration. UDCA-zein NPs ameliorated the symptoms of ALD mice remarkably, which were mainly exerted through attenuation of antioxidant stress levels. Meanwhile, it notably upregulated the intestinal tight junction protein expression and improved and maintained the integrity of the mucosal barrier effectively. Collectively, with the improvement of bioavailability, the UDCA-zein NPs prominently alleviated the oxidative damage induced by alcohol, modulating the inflammation so as to restore ALD. It is anticipated that UDCA-zein NPs have great therapeutic potential as sustained-nanovesicles in ALD treatment.

Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients' blood.

During cancer progression, tumorigenic and immune signals are spread through circulating molecules, such as cell-free DNA (cfDNA) and cell-free RNA (cfRNA) in the blood. So far, they have not been comprehensively investigated in gastrointestinal cancers. Here, we profile 4 categories of cell-free omics data from patients with colorectal cancer and patients with stomach adenocarcinoma and then assay 15 types of genomic, epigenomic, and transcriptomic variations. We find that multi-omics data are more appropriate for detection of cancer genes compared with single-omics data. In particular, cfRNAs are more sensitive and informative than cfDNAs in terms of detection rate, enriched functional pathways, etc. Moreover, we identify several peripheral immune signatures that are suppressed in patients with cancer. Specifically, we establish a γδ-T cell score and a cancer-associated-fibroblast (CAF) score, providing insights into clinical statuses like cancer stage and survival. Overall, we reveal a cell-free multi-molecular landscape that is useful for blood monitoring in personalized cancer treatment.

The Alleviating Effects and Mechanisms of Betaine on Dextran Sulfate Sodium-Induced Colitis in Mice.

SCOPE: Ulcerative colitis (UC) is an intestinal disease that is becoming increasingly prevalent and is often overlooked in early stages, and its pathogenesis is often closely related to inflammatory processes. Betaine is a natural product with anti-inflammatory effects that exists in a wide range of plants and animals. METHODS AND RESULTS: In this study, the protective effects of betaine are investigated on intestinal barrier function in a mouse model, a dextran sulfate sodium-induced ulcerative colitis and its mechanism of action in the inflammatory context. FITC-dextran 4000 Da (FD-4) flux, disease activity index, histopathological scores, and inflammatory factor levels in sera are determined across different groups. In addition, Caco-2 cell monolayer barrier function is evaluated by transepithelial resistance and FD-4 flux. The expression levels and distribution of tight junction proteins are determined using Western blot and immunofluorescence, respectively. Activation of the NF-κBp65/MLCK/p-MLC signaling pathway is detected by Western blot. Chromatin immunoprecipitation is performed to examine the binding of NF-κB to the MLCK gene promoter. The results indicated that betaine inhibits NF-κB-mediated activation of the MLCK/p-MLC signaling pathway to protect the intestinal barrier function of mice with UC. CONCLUSION: Betaine can be used as a potential candidate drug to improve intestinal barrier dysfunction in patients with UC.

Epithelioid inflammatory myofibroblastic sarcoma: a case report and brief literature review.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare variant of the inflammatory myofibroblastic tumor, characterized by more aggressive clinical course and nuclear membrane staining of anaplastic lymphoma kinase (ALK) with ALK rearrangement. An elderly male came to the clinic because of an accidental abdominal mass. Abdominal and pelvic enhanced CT revealed a tumor apparently orginated from mesenchymal tissue. Subsequently, the abdominal mass and multiple organ resection was performed, and the mass was pathologically confirmed as EIMS. The patient developed Clavien-Dindo Grade III postoperative complications and was discharged after his condition improved. He received doxorubicin monotherapy after operation, but only one cycle was administered due to severe vomiting. The follow-up of 5 months after operation showed no evidence of recurrence. Given the rarity of EIMS, and ALk inhibitors have a long and robust effect on patients with ALK gene tumors, it is very important for clinicians to be familiar with the clinicopathological features of EIMS, which will contribute to the accurate diagnosis of EIMS and reduce misdiagnosis.

Yiqi Chutan Formula Reverses Cisplatin-Induced Apoptosis and Ferroptosis of Skeletal Muscle by Alleviating Oxidative Stress.

BACKGROUND: Cisplatin is a widely used anticancer drug in clinic, but it has a damaging effect on skeletal muscle cells. Clinical observation showed that Yiqi Chutan formula (YCF) had a alleviating effect on cisplatin toxicity. METHODS: In vitro cell model and in vivo animal model were used to observe the damage effect of cisplatin on skeletal muscle cells and verify that YCF reversed cisplatin induced skeletal muscle damage. The levels of oxidative stress, apoptosis and ferroptosis were measured in each group. RESULTS: Both in vitro and in vivo studies have confirmed that cisplatin increases the level of oxidative stress in skeletal muscle cells, thus inducing cell apoptosis and ferroptosis. YCF treatment can effectively reverse cisplatin induced oxidative stress in skeletal muscle cells, thereby alleviating cell apoptosis and ferroptosis, and ultimately protecting skeletal muscle. CONCLUSIONS: YCF reversed cisplatin-induced apoptosis and ferroptosis of skeletal muscle by alleviating oxidative stress.

A novel immunogenic cell death-related subtype classification and risk signature for predicting prognosis and immunotherapy efficacy in gastric cancer.

The majority of gastric cancer (GC) patients are in a progressive stage at the initial stage of treatment, and the overall response rate to immunotherapy remains unsatisfactory largely due to the lack of effective prognostic biomarkers. Immunogenic cell death (ICD) was identified as a new form of regulated cell death that can activate adaptive immune responses and further promote immunotherapy efficacy. Therefore, we attempted to characterize the ICD-associated signature to stratify patients who could benefit from immunotherapy. In our study, two subgroups of patients were identified based on the data of 34 ICD-related genes extracted from The Cancer Genome Atlas database via consensus clustering. The estimated scores, stromal scores, immune scores, tumor purity, and survival rate showed significant differences between the low and high ICD groups. Then, we constructed an ICD-related risk signature, including IFNB1, IL6, LY96, and NT5E, using least absolute shrinkage and selection operator Cox regression analysis; then, high- and low-risk groups could be clearly distinguished. Notably, the risk score is a reliable predictor of the prognosis and immunotherapy outcome in GC, which was further validated in an immunohistochemistry assay. These results suggest that ICD is closely associated with the prognosis and tumor immune microenvironment in GC. Taken together, this study first constructed and validated a prognostic ICD-related signature to predict the survival and effect of immunotherapy in GC, which provided new insight for potent individualized immunotherapy strategies.

Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 axis in colorectal cancer cells.

Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its antitumor role remains to be elucidated. The aim of this study is to explore the mechanisms underlying the tumor suppressive activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 eliminates colorectal cancer (CRC) cells by activating gasdermin D (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in turn promotes NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively inhibits the proliferation of CRC cells in vitro and in nude mouse models. Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing great anticancer potential.

Appropriate time to radical surgery for colorectal cancer patients complicated with newly onset cerebral infarction: a propensity score matching analysis.

The purpose of our study was to compare the short-term outcomes of early (within 3 months after stroke) and nonearly (more than 3 months after stroke) radical colorectal cancer surgery to find an appropriate time to surgery for these colorectal cancer patients complicated with new-onset cerebral infarction. A retrospective analysis of patients with stroke who underwent curative colorectal cancer surgery between January 2010 and December 2020 was conducted. Propensity score matching (PSM) analysis was performed to overcome patient selection bias between the two groups. A total of 395 patients were reviewed. After PSM, 40 patients in the early group and 40 patients in the nonearly group were compared. The median time to surgery was 4 weeks in the early group. The overall incidence of postoperative complications between the groups was not significantly different (p = 0.745). The early group was associated with less intraoperative blood loss (50 vs. 100, p = 0.029 ml), with no difference in 30-day morbidity and mortality. Additionally, multivariate logistic regression analysis showed that previous abdominal surgery (p = 0.049) was an independent risk factor for postoperative complications after matching. Before matching, multivariate logistic analysis showed that ESRS (p = 0.028) and MRS (p = 0.039) were independent risk factors. Radical surgery after 4 weeks of cerebral infarction may be feasible for colorectal cancer patients with new onset stroke, as it appear not to increase the perioperative complications of Clavien-Dindo grade II or higher, while strengthening the preoperative evaluation and perioperative monitoring.

Deciphering the Molecular Mechanism of Yifei-Sanjie Pill in Cancer-Related Fatigue.

Background: The incidence of cancer-related fatigue (CRF) is increasing, but its lack of clear pathogenesis makes its prevention and treatment difficult. Therefore, it is of great significance to clarify the pathogenesis of CRF and find effective methods to treat it. Methods: The CRF model was established by intraperitoneal injection of LLC cells in ICR mice to explore the pathogenesis of CRF and verify the therapeutic effect of the Yifei-Sanjie pill (YFSJ). The active components of YFSJ were found by LC/MS, the in vitro inflammatory infiltration model of skeletal muscle was constructed by TNF-α and C2C12 myoblasts, and the results of in vivo experiments were verified by this model. Results: Behavioral analysis results showed that YFSJ alleviated CRF; histological examination results showed that YFSJ could reverse the tumor microenvironment leading to skeletal muscle injury; ELISA and RNA-seq results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the tumor inflammatory microenvironment; IHC and WB results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the Stat3-related signaling pathway and autophagy. Conclusions: YFSJ can reduce the level of inflammation in the tumor microenvironment in vivo, inhibit the abnormal activation of the Stat3/HIF-1α/BNIP3 signaling pathway induced by tumor-related inflammation, thereby inhibiting the overactivation of mitophagy in skeletal muscle, and finally alleviate CRF. Quercetin, one of the components of YFSJ, plays an important role in inhibiting the phosphorylation activation of Stat3.

Survival comparison of stage IIA rectal cancer with or without neoadjuvant therapy: a SEER database analysis with propensity score matching.

Background: Patients with stage IIA rectal cancer have a higher survival rate but side effects from chemoradiotherapy; thus, whether neoadjuvant therapy should be performed for stage IIA rectal cancer is controversial. This study aimed to compare the survival outcomes of patients with stage IIA rectal cancer with or without neoadjuvant chemoradiotherapy. Methods: Patients with stage IIA rectal cancer between 2010 and 2015 were included through the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to reduce the impact of confounding factors. Survival curves were plotted using the Kaplan-Meier method, and survival differences were assessed using the log-rank test. Results: There were no significant differences in overall survival and cancer-specific survival between the neoadjuvant chemoradiotherapy and surgery groups (P=0.973 and 0.983). Compared with the surgery group, the neoadjuvant chemoradiotherapy + surgery + chemotherapy group had a better overall survival (P=0.007). Subgroup analysis showed that the neoadjuvant chemoradiotherapy + surgery + chemotherapy group had better overall survival compared to the surgery group in the subgroup containing preoperative high-risk factors (P=0.003) but not in the low-risk subgroup (P=0.685). Conclusions: There is no evidence that neoadjuvant chemoradiotherapy + surgery can improve overall survival and cancer-specific survival compared to surgery alone in patients with stage IIA rectal cancer. Neoadjuvant chemoradiotherapy + surgery + chemotherapy can improve overall survival compared to surgery alone, but only in patients with preoperative high-risk factors. We suggest that patients with no preoperative high-risk factors may be considered for surgery alone, neoadjuvant chemoradiotherapy + surgery + chemotherapy is recommended for patients with preoperative risk factors.

Yifei sanjie Pills Alleviate Chemotherapy-Related Fatigue by Reducing Skeletal Muscle Injury and Inhibiting Tumor Growth in Lung Cancer Mice.

Chemotherapy-related fatigue (CRF), one of the most severe adverse effects observed in cancer patients, has been theoretically related to oxidative stress, and antioxidant treatment might be one of the most valuable therapeutic approaches. However, there are still few effective pharmacological therapies. Yifei Sanjie pills (YFSJ), a classical formula used to treat lung cancer as complementary and alternative medicine, have been proved to alleviate CRF of lung cancer patients in clinical practices. However, the underlying mechanisms have not been clarified. In this study, our data showed that YFSJ alleviated CRF presented as reversing the decline of swimming time and locomotor activity induced by cisplatin (DDP). Moreover, YFSJ significantly reduces the accidence of mitophagy and mitochondrial damage and reduces apoptosis in skeletal muscle tissues caused by DDP. It probably works by decreasing the oxidative stress, inhibiting the activation of the AMPK/mTOR pathway, decreasing protein expression levels of Beclin1 and other autophagy-related proteins, and attenuating the activation of Cytochrome c (cyto. C), Cleaved Caspase-9 (c-Casp 9), and other apoptosis-related proteins. Furthermore, YFSJ enhanced DDP sensitivity by specifically promoting oxidative stress and activating apoptosis and autophagy in the tumor tissues of mice. It was also found that YFSJ reduced the loss of body weight caused by DDP, reversed the ascent of serum concentrations of alanine aminotransferase (ALT), aminotransferase (AST), and creatinine (CREA), increased the spleen index, and prolonged the survival time of mice. Taken together, these results revealed that YFSJ could alleviate CRF by reducing mitophagy and apoptosis induced by oxidative stress in skeletal muscle; these results also displayed the effects of YFSJ on enhancing chemotherapy sensitivity, improving quality of life, and prolonging survival time in lung cancer mice received DDP chemotherapy.

Luteolin induces pyroptosis in HT-29 cells by activating the Caspase1/Gasdermin D signalling pathway.

Luteolin, which is a natural flavonoid, has anti-inflammatory, antioxidant, and anticancer properties. Numerous studies have proven that luteolin inhibits the growth of many types of cancer cells by promoting apoptosis, autophagy, and cell cycle arrest in tumour cells. However, in vivo research on this topic has been limited. In addition, other studies have shown that luteolin exerts a good inhibitory effect on apoptosis-resistant cancer cells. While existing studies have not completely elucidated the mechanism underlying this phenomenon, we assume that luteolin, which is a natural compound that exerts its effects through various mechanisms, may have the potential to inhibit tumour growth. In our study, we proved that luteolin exerted a good inhibitory effect on the proliferation of colon cancer cells according to CCK8 and EdU fluorescence assays, and the same conclusion was drawn in animal experiments. In addition, we found that luteolin, which is an antioxidant, unexpectedly promoted oxidative stress as shown by measuring the levels of oxidative balance-related indicators, such as reactive oxygen species (ROS), SOD, H2O2 and GSH. However, the decreased oxidation of luteolin-treated HT-29 cells after treatment with the active oxygen scavenger NAC did not reverse the inhibition of cell growth. However, the Caspase1 inhibitor VX765 did reverse the inhibition of cell growth. Western blotting analysis showed that luteolin treatment increased the expression of Caspase1, Gasdermin D and IL-1ß, which are members of the pyroptosis signalling pathway, in colon cancer cells. We further intuitively observed NLRP3/Gasdermin D colocalization in luteolin-treated HT-29 cells and mouse tumour tissues by immunofluorescence. These results suggest that luteolin inhibits the proliferation of colon cancer cells through a novel pathway called pyroptosis. This study provides a new direction for the development of natural products that inhibit tumour growth by inducing pyroptosis.

Cancer type classification using plasma cell-free RNAs derived from human and microbes.

The utility of cell-free nucleic acids in monitoring cancer has been recognized by both scientists and clinicians. In addition to human transcripts, a fraction of cell-free nucleic acids in human plasma were proven to be derived from microbes and reported to have relevance to cancer. To obtain a better understanding of plasma cell-free RNAs (cfRNAs) in cancer patients, we profiled cfRNAs in ~300 plasma samples of 5 cancer types (colorectal cancer, stomach cancer, liver cancer, lung cancer, and esophageal cancer) and healthy donors (HDs) with RNA-seq. Microbe-derived cfRNAs were consistently detected by different computational methods when potential contaminations were carefully filtered. Clinically relevant signals were identified from human and microbial reads, and enriched Kyoto Encyclopedia of Genes and Genomes pathways of downregulated human genes and higher prevalence torque teno viruses both suggest that a fraction of cancer patients were immunosuppressed. Our data support the diagnostic value of human and microbe-derived plasma cfRNAs for cancer detection, as an area under the ROC curve of approximately 0.9 for distinguishing cancer patients from HDs was achieved. Moreover, human and microbial cfRNAs both have cancer type specificity, and combining two types of features could distinguish tumors of five different primary locations with an average recall of 60.4%. Compared to using human features alone, adding microbial features improved the average recall by approximately 8%. In summary, this work provides evidence for the clinical relevance of human and microbe-derived plasma cfRNAs and their potential utilities in cancer detection as well as the determination of tumor sites.

Appendico-vesicocolonic fistula: A case report and review of literature.

BACKGROUND: Appendico-vesicocolonic fistulas and appendiceal-colonic fistulas are two kinds of intestinal and bladder diseases that are rarely seen in the clinic. To our knowledge, no more than 4 cases of appendico-vesicocolonic fistulas have been publicly reported throughout the world, and no more than 100 cases of appendiceal-colonic fistulas have been reported. Although the overall incidence is low, an early diagnosis is difficult due to their atypical initial symptoms, but these diseases still require our attention. CASE SUMMARY: Here, we report a case of a 77-year-old male patient diagnosed with an appendico-vesicocolonic fistula combined with an appendiceal-colonic fistula. The main manifestations were diarrhea and urine that contained fecal material. The diagnosis was confirmed by multiple laboratory and imaging examinations. A routine urinalysis showed red blood cells and white blood cells. Abdominal and pelvic computed tomography scans showed close adhesions between the bowels and the bladder, and fistulas could be seen. Colonoscopy and cystoscopy and some other imaging examinations clearly showed fistulas. The preoperative diagnoses were a colovesical fistula and an appendiceal-colonic fistula. The fistulas were repaired by laparoscopic surgical treatment. The diseased bowel and part of the bladder wall were removed, followed by a protective ileostomy. The postoperative diagnosis was an appendico-vesicocolonic fistula combined with an appendiceal-colonic fistula, and the pathology suggested inflammatory changes. The patient recovered well after surgery, and all his symptoms resolved. CONCLUSION: The final diagnosis in this case was a double fistula consisting of an appendico-vesicocolonic fistula combined with an appendiceal-colonic fistula.

Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in colorectal cancer.

BACKGROUND: It is generally accepted that colorectal cancer (CRC) originates from cancer stem cells (CSCs), which are responsible for CRC progression, metastasis and therapy resistance. The high heterogeneity of CSCs has precluded clinical application of CSC-targeting therapy. Here, we aimed to characterize the stemness landscapes and screen for certain patients more responsive to immunotherapy. METHODS: Twenty-six stem cell gene sets were acquired from StemChecker database. Consensus clustering algorithm was applied for stemness subtypes identification on 1,467 CRC samples from TCGA and GEO databases. The differences in prognosis, tumor microenvironment (TME) components, therapy responses were evaluated among subtypes. Then, the stemness-risk model was constructed by weighted gene correlation network analysis (WGCNA), Cox regression and random survival forest analyses, and the most important marker was experimentally verified. RESULTS: Based on single-sample gene set enrichment analysis (ssGSEA) enrichments scores, CRC patients were classified into three subtypes (C1, C2 and C3). C3 subtype exhibited the worst prognosis, highest macrophages M0 and M2 infiltrations, immune and stromal scores, and minimum sensitivity to immunotherapies, but was more sensitive to drugs like Bosutinib, Docetaxel, Elesclomol, Gefitinib, Lenalidomide, Methotrexate and Sunitinib. The turquoise module was identified by WGCNA that it was most positively correlated with C3 but most negatively with C2, and five hub genes in turquoise module were identified for stemness model construction. CRC patients with higher stemness scores exhibited worse prognosis, more immunosuppressive components in TME and lower immunotherapeutic responses. Additionally, the model's immunotherapeutic prediction efficacy was further confirmed from two immunotherapy cohorts (anti-PD-L1 in IMvigor210 cohort and anti-PD-1 in GSE78220 cohort). Mechanistically, Gene Set Enrichment Analysis (GSEA) results revealed high stemness score group was enriched in interferon gamma response, interferon alpha response, P53 pathway, coagulation, apoptosis, KRAS signaling upregulation, complement, epithelial-mesenchymal transition (EMT) and IL6-mediated JAK-STAT signaling gene sets. CONCLUSIONS: Our study characterized three stemness-related subtypes with distinct prognosis and TME patterns in CRC patients, and a 5-gene stemness-risk model was constructed by comprehensive bioinformatic analyses. We suggest our stemness model has prospective clinical implications for prognosis evaluation and might facilitate physicians selecting prospective responders for preferential use of current immune checkpoint inhibitors.