Colorectal cancer (CRC) is the third most frequently diagnosed cancer, with rectal cancer (RC) accounting for approximately 35 % of cases, posing a significant health burden. The early phase of R progression is characterized by the accumulation of genetic and epigenetic changes that promote cell growth. These rapidly dividing cells form a benign adenoma, which can eventually transform into malignant tumors and metastasize to other organs. Among the key molecular alterations, a mutation in the Wnt/β-catenin signaling pathway plays a crucial role. Additionally, BRAF mutation contributes to 8-10 % of CRC cases, while mutation in PIK3C pathways is responsible for 20-25 % of cases. The RC involves complex biological mechanisms. This review article highlights the pivotal role of mRNA in diagnosing and predicting the prognosis of RC, explores the various functions of non-coding RNAs (ncRNA,s), and examines the impact of RNA editing and modification on the progression of tumor genesis. Furthermore, we discuss the cellular signaling pathways and microenvironment interaction and pathways like PI3K/Akt/mTOR and Wnt/β-catenin. Advancements in molecular, RNA, and genetic research have evolved the treatment of cancer. Techniques like next-generation sequencing have tremendously opened the biological field of research. Along with this, techniques like CRISPR/Cas9 aid in the developing therapeutic strategies. Proteomics and metabolomics approach further contribute to novel research direction in oncology.

Colorectal cancer (CRC) is linked to the WNT/β-catenin signaling as its primary driver. Aberrant activation of WNT/β-catenin signaling is closely correlated with increased incidence, malignancy, poorer prognosis, and even higher cancer-related death. Research over the years has postulated various experimental models that have facilitated an understanding of the complex mechanisms underlying WNT signaling in CRC. In the present review, we have comprehensively summarized the in vitro, in vivo, patient-derived, and computational models used to study the role of WNT signaling in CRC. We discuss the use of CRC cell lines and organoids in capturing the molecular intricacies of WNT signaling and implementing xenograft and genetically engineered mouse models to mimic the tumor microenvironment. Patient-derived models, including xenografts and organoids, provide valuable insights into personalized medicine approaches. Additionally, we elaborated on the role of computational models in simulating WNT signaling dynamics and predicting therapeutic outcomes. By evaluating the advantages and limitations of each model, this review highlights the critical contributions of these systems to our understanding of WNT signaling in CRC. We emphasize the need to integrate diverse model systems to enhance translational research and clinical applications, which is the primary goal of this review.

Cancer cells undergo metabolic reprogramming, shifting their programs toward aerobic glycolysis and enhanced glutaminolysis to fulfill the requirements of rapid proliferation. Investigating the mechanisms underlying glutaminolysis and its connection with colorectal cancer (CRC) could aid in identifying novel therapeutic targets. PTCD3, a mitochondrial RNA-binding protein, is implicated in cancer progression, and IGF2BP2 regulates mRNA stability and translation. SLC38A2, a key transporter in glutamine metabolism, plays a crucial role in supporting cancer cell growth. This study aims to develop inhibitors of PTCD3 or SLC38A2 to prevent metabolic changes in cancer cells that facilitate rapid growth and metastasis in CRC. RT-qPCR, western blot, IHC, and IF staining assays confirmed the targeted gene and protein expression. Proliferation, migration, and invasion were evaluated using CCK-8 assay, scratch assay, and Transwell assay, respectively. Co-IP, RIP, and dual-luciferase assays were conducted to investigate the interactions among PTCD3, IGF2BP2, and SLC38A2. A CRC xenograft nude mice model was established for additional in vivo validation. PTCD3 was upregulated in CRC and positively correlated with GLS1. PTCD3 knockdown suppressed CRC cell glutaminolysis, thereby inhibiting CRC migration and invasion. PTCD3 promoted SLC38A2 mRNA stability in an IGF2BP2-dependent manner. KAT2A promoted the expression of PTCD3 by increasing H3K27 acetylation. The inhibitory effect of PTCD3 depletion on the glutaminolysis of CRC cells, as well as CRC cell proliferation and migration, was reversed by SLC38A2 overexpression. The in vivo mouse experiments further confirmed that silencing of PTCD3 inhibited CRC tumor growth. In summary, KAT2A upregulates PTCD3 expression by promoting H3K27 acetylation, which promotes glutaminolysis and metastasis in CRC via enhancing SLC38A2 mRNA stability in an IGF2BP2-dependent manner.

Colorectal cancer (CRC) is a significant global health challenge, marked by varying incidence and mortality rates across different regions. The pathogenesis of CRC involves multiple stages, including initiation, promotion, progression, and metastasis, influenced by genetic and epigenetic factors. The chaperone protein glucose-regulated protein 78 (GRP78), crucial in regulating the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, plays a pivotal role in CRC pathogenesis. This review discusses the expression profile of GRP78 in CRC, highlighting its potential as a prognostic biomarker and its role in modulating the cellular mechanisms of CRC, including ER response regulation, cell proliferation, migration and invasion. The complex molecular interactions of GRP78 with key signaling pathways such as protein kinase B (Akt), Wnt, protein kinase R-like ER kinase (PERK), vascular endothelial growth factor (VEGF), and Kirsten rat sarcoma virus (Kras) are explored, elucidating its contributions to tumor survival, proliferation, invasion, and chemoresistance. GRP78's involvement in autophagy, glycolysis, and immune regulation further underscores its importance in CRC progression. The review also covers the therapeutic potential of targeting GRP78 in CRC, examining various natural products like curcumin, epigallocatechin gallate (EGCG), and aloe-emodin, which modulate GRP78 expression and activity. Additionally, GRP78's role in mediating resistance to chemotherapeutic agents like 5-fluorouracil (5-FU) and oxaliplatin is discussed, emphasizing its significance in the development of resistance mechanisms in CRC. In conclusion, GRP78 emerges as a central player in CRC pathogenesis and a promising target for therapeutic interventions aimed at improving treatment outcomes and overcoming chemoresistance in colorectal cancer.

Polyp size is crucial for determining colonoscopy surveillance intervals. We present an artificial intelligence (AI) model for colorectal polyp size measurement without a reference object.

The regression model for polyp size estimation was developed using outputs from two SegFormer models, segmentation and depth estimation. Initially built on colonoscopic images of polyp phantoms, the model underwent transfer learning with 1,304 real-world images. Testing was conducted on 178 images from 52 polyps, independent of the training set, using a snare as the ground truth for size comparison with the AI-based model. Polyps were classified into three size groups: ≤ 5 mm, 5-10 mm, and ≥ 10 mm. Error rates were calculated to evaluate discrepancies in actual size values between the AI model and the snare method. Precision indicated the positive predictive value per size group and recall and Bland-Altman were also conducted.

The Bland-Altman analysis showed a mean bias of -0.03 mm between methods, with limits of agreement from -1.654 mm to 1.596 mm. AI model error rates for actual size discrepancies were 10.74%, 12.36%, and 9.89% for the ≤ 5 mm, 5-10 mm, and ≥ 10 mm groups, respectively, averaging 11.47%. Precision values were 0.870, 0.911, and 0.857, with overall recall of 0.846.

Our study shows that colorectal polyp size measurement by AI model is practical and clinically useful, exhibiting low error rates and high precision. AI shows promise as an accurate tool for measurement without the need for a reference object during screening colonoscopy.

Colorectal cancer (CRC), the third most common cancer worldwide, is one of the deadliest cancers. CRC is known as a cold tumor, characterized by a low immune response that makes it difficult for immune cells to infiltrate and exhibits strong resistance to immunotherapy with checkpoint inhibition. This restricted response is largely attributed to signature gene mutations including mismatch repair (MMR) genes, KRAS, BRAF, APC, and TP53, which are also the main oncogenes in CRC. Mutated signature genes continuously upregulate abnormal signaling pathways, leading to excessive proliferation, cancer progression, and metastasis. Furthermore, it reorganizes the tumor microenvironment (TME) by recruiting immunosuppressive cells. However, the mutation can produce neoantigens that can provoke an immune response, making it a potential target for immunotherapy. In particular, cancer vaccines that leverage the strong neoantigenic properties of these mutations are considered promising for overcoming immune resistance and eliciting anti-tumor responses. In this review, we will describe signature gene mutations in CRC and focus on cancer vaccines targeting these mutations as potential therapies for CRC.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low. Traditional two-dimensional (2D) cell culture systems have been the foundation of cancer research, but their inability to replicate the complex tumor microenvironment (TME) limits their effectiveness.

This paper explores the evolution of CRC models, starting with the limitations of traditional 2D cell culture systems and the significant advancements offered by 3D models. Additionally, it highlights 3D bioprinting and on-chip CRC models, which have enhanced the ability to mimic in vivo conditions.

The transition to advanced 3D models represents a pivotal shift in CRC research, offering considerable improvements over the established 2D models. These models hold promise for the development of patient-specific models that better mimic in vivo conditions. However, the inherent complexity of CRC continues to pose challenges in developing models that can fully capture the disease's multifaceted nature. This complexity and high costs associated with these technologies, along with the need for standardized protocols, pose significant challenges to their widespread adoption.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality globally and presents significant challenges in treatment and patient care. Capecitabine, a widely used prodrug of 5-fluorouracil (5-FU), offers targeted delivery with reduced systemic toxicity compared to traditional chemotherapies. However, capacitabine is associated with adverse effects, such as hand-foot syndrome, gastrointestinal issues, and mucositis. Emerging evidence suggests that probiotics, particularly Bifidobacterium, play a pivotal role in gut microbiota modulation, promoting anti-inflammatory cytokines and short-chain fatty acids, such as butyrate, which possess both intestinal protective and anti-cancer properties. In this review, we explored the potential of Bifidobacterium to improve chemotherapy outcomes by mitigating inflammation and enhancing mucosal immunity in CRC patients. Furthermore, we demonstrated in silico approaches, including molecular docking and protein-protein interaction analysis, for Bifidobacterium and Toll-like receptor 2 (TLR-2), a key mediator of intestinal immunity. Docking results revealed strong binding affinity, suggesting the activation of anti-inflammatory pathways. Notably, this interaction enhanced IL-10 production while reducing pro-inflammatory cytokines, such as IL-6 and TNF-α, fostering gut homeostasis and mitigating chronic inflammation, a key driver of CRC progression. Therefore, future research should focus on personalized probiotics and validating their synergy with chemotherapy and immunotherapy to improve CRC treatment outcomes.

Colorectal cancer (CRC) progression occurs through three stages: adenoma (pre-cancerous lesion), carcinoma in situ (CIS) and adenocarcinoma, with tumor stage playing a pivotal role in the prognosis and treatment outcomes. Despite therapeutic advancements, the lack of stage-specific biomarkers hinders the development of accurate diagnostic tools and effective therapeutic strategies. This study aims to identify stage-specific gene expression profiles and key molecular mechanisms in CRC providing insights into molecular alterations across disease progression. Our methodological approach integrates the use of absolute gene set enrichment analysis (absGSEA) on formalin-fixed paraffin-embedded (FFPE)-derived transcriptomic data, combined with large-scale clinical validation and experimental confirmation. A comparative whole transcriptomic analysis (RNA-seq) was performed on FFPE samples including adenoma (n = 10), carcinoma in situ (CIS) (n = 8) and adenocarcinoma (n = 11) samples. Using absGSEA, we identified significant cellular pathways and putative molecular biomarkers associated with each stage of CRC progression. Key findings were then validated in a large independent CRC patient cohort (n = 1926), with survival analysis conducted from 1336 patients to assess the prognostic relevance of the candidate biomarkers. The key differentially expressed genes were experimentally validated using real-time PCR (RT-qPCR). Pathway analysis revealed that in CIS, apoptotic processes and Wnt signaling pathways were more prominent than in adenoma samples, while in adenocarcinoma, transcriptional co-regulatory mechanisms and protein kinase activity, which are critical for tumor growth and metastasis, were significantly enriched compared to adenoma. Additionally, extracellular matrix organization pathways were significantly enriched in adenocarcinoma compared to CIS. Distinct gene signatures were identified across CRC stages that differentiate between adenoma, CIS and adenocarcinoma. In adenoma, ARRB1, CTBP1 and CTBP2 were overexpressed, suggesting their involvement in early tumorigenesis, whereas in CIS, RPS3A and COL4A5 were overexpressed, suggesting their involvement in the transition from benign to malignant stage. In adenocarcinoma, COL1A2, CEBPZ, MED10 and PAWR were overexpressed, suggesting their involvement in advanced disease progression. Functional analysis confirmed that ARRB1 and CTBP1/2 were associated with early tumor development, while COL1A2 and CEBPZ were involved in extracellular matrix remodeling and transcriptional regulation, respectively. Experimental validation with RT-qPCR confirmed the differential expression of the candidate biomarkers (ARRB1, RPS3A, COL4A5, COL1A2 and MED10) across the three CRC stages reinforcing their potential as stage-specific biomarkers in CRC progression. These findings provide a foundation to distinguish between the CRC stages and for the development of accurate stage-specific diagnostic and prognostic biomarkers, which helps in the development of more effective therapeutic strategies for CRC.

The quality of colonoscopy is significantly influenced by the effectiveness of bowel preparation. In this study, we aimed to evaluate the efficacy, safety, and tolerability of bowel cleansing between a new oral sulfate solution (OSS) and standard polyethylene glycol electrolyte powder (PEG).

This single center, randomized, superiority study recruited 679 outpatients who were assigned to either the new OSS group (Group A) or standard PEG group (Group B). The quality of bowel cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS) and compared between the two groups. Furthermore, data pertaining to the duration of bowel preparation, patient tolerability, and the occurrence of adverse events were also analyzed.

According to BBPS scores, group A demonstrated significantly higher bowel preparation cleanliness than group B. Additionally, group A achieved superior bowel cleansing, as evidenced by a greater proportion of patients with BBPS scores ≥ 8 compared to group B (75.3% vs. 55.2%, P < 0.05). No severe adverse events were reported during examinations in either group.

The magnesium sulfate, sodium sulfate, and potassium sulfate concentrated oral solution is a novel, safe, and effective bowel preparation for colonoscopy.

This study was registered in the Chinese Clinical Trial Registry on 20/02/2024 (clinical trial registration number: ChiCTR2400081004).

Exploring the anti-tumor molecular mechanisms of traditional Chinese medicines has become an important strategy to develop novel anti-tumor drugs in the clinic. Several pharmacological studies have reported the antioxidant, antibacterial, anti-inflammatory, and anti-tumor effects of clove. Previously, we have shown that the active fraction from clove (AFC) can inhibit the growth of tumor cells, particularly colon cancer cells, in vitro. However, the mechanism of action regarding the anti-colon cancer activity of AFC, especially in aerobic glycolysis, has not been adequately investigated. In this study, we found that AFC significantly inhibited the growth of five types of colon cancer cells, downregulated the mRNA and protein levels of M2-type pyruvate kinase (PKM2), and reduced aerobic glycolysis capacity. Transfection of PKM2-siRNA mimicked the inhibitory effects of AFC on aerobic glycolysis in colon cancer cells. Furthermore, the highly expressed, tumor-specific targets c-myc and cyclin D1 in cells were also found to be downregulated following the action of AFC. In the HCT116 cell xenograft nude mice models, the results after AFC administration were consistent with those of the cellular experiments, while AFC caused less liver injury and weight loss than the conventional chemotherapeutic agent 5- fluorouracil (5-FU). In conclusion, AFC inhibits colon cancer growth by downregulating PKM2 to inhibit aerobic glycolysis and reduce the tumor-specific high expression of c-myc and cyclin D1. Future work should explore how it downregulates pyruvate kinase (PK) in the first place, along with the intrinsic mechanism between the downregulation of PKM2 and the downregulation of c-myc.

Colorectal cancer (CRC) is a common malignancy that has become a global burden. The prognostic prediction of CRC patients on the basis of inflammatory biomarkers and nutritional biomarkers has shown some potential but has not been fully explored.

To develop and validate a prognostic model for CRC based on inflammation and nutrition-related biomarkers and to evaluate its predictive value for patient outcomes.

Patients were randomized at a 3:2 ratio into a training cohort (n = 282) or a validation cohort (n = 188). To identify the optimal prognostic factors for constructing the risk score (RS), LASSO Cox regression analysis was conducted. The association between the RS and overall survival (OS) was evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival analysis. Independent risk factors were screened by multivariate Cox regression analysis. Nomograms were constructed and validated on the basis of these factors.

In the training cohort, univariate analysis of all the inflammatory and nutritional biomarkers demonstrated some predictive value. A LASSO-Cox analysis included four biomarkers and constructed an RS. Through ROC analysis, the area under the prognostic curve was 0.795. K-M survival curve analyses revealed that the five-year OS was significantly greater in the Low-RS group than in the High-RS group (P < 0.001). Multivariate analysis demonstrated that the degree of differentiation (P = 0.001), degree of nerve invasion (P = 0.022), and RS (P < 0.001) were independent risk factors. We constructed a nomogram to predict the OS of CRC patients and validated it in a separate cohort. The calibration curve showed high accuracy. Additionally, decision curve analysis for 1-year, 3-year, and 5-year survival probabilities indicated significant clinical utility in predicting survival outcomes.

This study developed a nomogram based on the RS to predict the OS of CRC patients. This nomogram can guide treatment decisions and enable the formulation of personalized follow-up strategies on the basis of predicted recurrence risk, aiming to improve long-term prognosis.

Colorectal carcinoma (CRC) is a leading cause of cancer-related deaths globally. Diagnostic biomarkers are essential for risk stratification and early detection, potentially enhancing patient survival. Our study aimed to explore the potential biomarkers of CRC at the protein and metabolic levels.

Blood serum from CRC patients and healthy controls was analyzed using metabolomic and proteomic techniques. A conjoint analysis was conducted, and samples were split into training and validation sets (7:3 ratio) to develop and evaluate a disease diagnosis classifier model. Immunohistochemistry (IHC) analyses were conducted to validate the results.

We identified 631 differential metabolites and 61 differentially expressed proteins (DEPs) in CRC, involved in pathways such as arginine and proline metabolism, central carbon metabolism in cancer, and signaling pathways including TGF-β, mTOR, PI3K-Akt, and others. Key proteins (CILP2, SLC3A2, EXTL2, hydroxypyruvate isomerase (HYI), ENPEP, LRG1, CTSS, thyrotropin-releasing hormone-degrading ectoenzyme (TRHDE), SELE, and HSPA1A) showed significant expression differences between CRC patients and controls. IHC results showed that compared with the paracancerous tissues, the expression of CILP2, EXTL2, and HYI was significantly downregulated in the CRC tissues (P < 0.05). The classifier model, comprising l-arginine, Harden-Young ester, l-aspartic acid, oxoglutaric acid, l-proline, octopine, l-valine, and progesterone, achieved AUC values of 0.998 and 0.914 in training and validation data sets, respectively.

The identified metabolites and DEPs are promising CRC biomarkers. The developed classifier model based on eight metabolites demonstrates high accuracy for CRC assessment and diagnosis.

Colorectal cancer (CRC) is a prevalent malignancy of the digestive system. Here, we explored the role of M2 macrophage-derived extracellular vesicles (EVs) carrying long non-coding RNA-nuclear paraspeckle assembly transcript 1 (lncRNA-NEAT1) in promoting CRC progression via regulation of the miR-204-5p/regulator of ribosome synthesis 1 (RRS1) axis and cell cycle dynamics. Firstly, we differentiated WTHP-1 cells into M0 and M2 macrophages and transfected M2 macrophages with sh-NEAT1 lentivirus plasmids. EVs were isolated from M2 macrophages and administered to SW480 cells along with miR-204-5p inhibitors or si-RRS1 for 24 h. M2-EVs-derived lncRNA-NEAT1 enhanced CRC cell proliferation, migration, invasion, and viability while reducing apoptosis. This was accompanied by increased expression of RRS1, WEE1 G2 checkpoint kinase (WEE1), cyclin-dependent kinase 1 (CDK1), and CyclinB1, reduced miR-204-5p levels, and a lower proportion of cells in the G2/M phase. Knockdown of lncRNA-NEAT1 in M2 macrophages reversed these effects. Mechanistically, M2-EVs-derived lncRNA-NEAT1 functioned as a competing endogenous RNA (ceRNA), sponging miR-204-5p to upregulate RRS1 expression. In summary, M2 macrophage-derived EVs carrying lncRNA-NEAT1 promote CRC development by modulating the miR-204-5p/RRS1 axis, influencing the cell cycle and apoptosis. These findings provide insights into the tumor-promoting mechanisms of macrophage-derived EVs in CRC.

Mitochondrial-encoded circular RNAs (mecciRNAs) are a newly discovered class of mitochondrial-encoded non-coding RNAs (mt-ncRNAs) that play important biological roles in the cell. This study aimed to examine the expression profile of SCAR/mc-COX2 (has_circ_0089762) in colorectal cancer (CRC) and its relationship with clinicopathological variables. Furthermore, to better understand SCAR/mc-COX2's functional role in CRC, we constructed a competing endogenous RNA (ceRNA) network.

Quantitative real-time PCR (qRT-PCR) was employed to analyze the expression levels of SCAR/mc-COX2 in 40 pairs of CRC samples, consisting of 40 tumor samples and 40 adjacent non-tumoral samples from patients. The ceRNA regulatory network was constructed using online bioinformatics tools. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) enrichment analysis were conducted using the Enrichr database.

The results demonstrated a significant decrease in SCAR/mc-COX2 expression in tumor tissues compared to adjacent non-tumoral tissues (p-value<0.05). In another finding, a significant relationship was observed between pathological T staging and the expression status of SCAR/mc-COX2 (p-value=0.02). Additionally, the Receiver Operating Characteristic (ROC) curve analysis revealed that SCAR/mc-COX2 had an area under the curve (AUC) of 0.77, with 80% sensitivity and 75% specificity. Finally, a ceRNA regulatory network including SCAR/mc-COX2, 5 miRNA, and 9 mRNAs was found.

These findings suggest that SCAR/mc-COX2 may act as a tumor suppressor in CRC, and its dysregulation could play a crucial role in the pathophysiology of this cancer. The significant association with pathological T staging and its robust diagnostic performance (AUC = 0.77, sensitivity = 80%, specificity = 75%) highlight its potential as a novel biomarker for CRC detection and prognosis. Further functional studies are required to elucidate its precise role in CRC tumorigenesis and clinical applicability.

Gastrointestinal tract cancers represent a significant worldwide health concern, accounting for almost one-third of cancer-related deaths. The existing chemotherapy drugs used in gastrointestinal cancers are ineffective, so prognosis is poor, recurrence and metastasis rates are high, and survival time remains short, necessitating the development of novel antitumor drugs that exhibit low toxicity and less potential for the development of drug resistance. This challenge is considerable, but evidence from the past decades supports the medicinal properties and functionalities of bioactive compounds such as flavonoids and acid phenolics with anticancer activities. Our purpose was to find data on the relationship between gastrointestinal cancer and bioactive compounds from Prunus species, focusing on their molecular mechanisms of action.

Studies highlight the potential of bioactive compounds from Prunus species to modulate the cancer cell signaling pathways involved in gastrointestinal tumorigenesis.

The studies reviewed suggest that polyphenols from Prunus species exhibit promising gastrointestinal anticancer activities and could represent an adjunctive therapeutic strategy in cancer treatment. Further studies are necessary to validate these compounds' therapeutic potential and their feasibility as cost-effective treatments for cancer.

Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: Curcuma longa, Astragalus membranaceus, Glycyrrhiza glabra, Althaea officinalis, Echinacea purpurea, Sanguinaria canadensis, Codonopsis pilosula, Hydrastis canadensis, Lobelia inflata, Scutellaria baicalensis, and Zingiber officinale. These plants were selected based on their documented use in traditional medicine and modern clinical practice. Selection criteria involved cross-referencing herbs identified in a scoping review of traditional cancer treatments and findings from an international survey on herbal medicine currently used for lung and colorectal cancer management by our research group and the availability of existing literature on their anticancer properties. The review identifies several isolated phytoconstituents from these plants that exhibit anticancer properties by modulating key signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, and TGF-β in vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric acid, glycyrrhizin, 18-β-glycyrrhetinic acid, astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, and glycyrol. Curcumin and baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome by combining them with piperine or using oral extracts to enhance gut microbiome conversion, integrating traditional knowledge with modern strategies for improved outcomes. Furthermore, herbal extracts from Echinacea, Glycyrrhiza, and Codonopsis, identified in traditional knowledge, are currently in clinical trials. Notably, curcumin and baicalin also modulate miRNA pathways, highlighting a promising intersection of modern science and traditional medicine. Thus, the development of anticancer therapeutics continues to benefit from the synergy of traditional knowledge, scientific innovation, and technological advancements.

To explore the effective components of Guishao Yigong decoction (GYD) in the treatment of colorectal cancer and reveal its potential mechanism of action.

Through network pharmacology, the main target and signaling pathway of GYD therapy for colorectal cancer (CRC) were found. Subsequently, the effect of GYD was verified by in vitro cell viability measurements, colony formation, and scratch healing tests. The effects of GYD on metabolic pathways in vivo were found through plasma metabolomics. Finally, flow cytometry and qPCR experiments were used to verify the cycle-blocking effect of GYD on CRC cells.

Based on the network pharmacological analysis and molecular docking technology, it was found that GYD could restrain the growth of CRC cells by affecting lipid metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathways. A series of cell experiments showed that GYD could inhibit the proliferation, migration and clonogenic ability of CRC cells. Furthermore, the plasma metabolomics results showed that GYD could affect the production of unsaturated fatty acids in mice. Flow cytometry and qPCR experiments further proved that GYD blocked the CRC cells in the G1 phase and modulated the expression of cell cycle-related targets, such as AKT, TP53, CDKN1A, and CDK2.

All the results indicated that GYD could regulate the related metabolism of unsaturated fatty acids. Thus, the cell cycle was blocked and the expressions of the key proteins such as AKT and TP53 were regulated, which achieved the purpose of intervention in colorectal cancer.

Globally, colorectal cancer (CRC) continues to rank among the leading causes of cancer-related death. Systemic toxicity, multidrug resistance, and nonspecific targeting often pose challenges to conventional therapy for CRC. Because it is a complex disease with a complex genetic and environmental pathophysiology, advanced therapeutic strategies are needed. Nanotechnology presents a potential solution that may maximize therapeutic efficacy while minimizing negative effects by enabling personalized delivery of anticancer drugs. This review focuses on recent developments in colorectal drug delivery systems based on nanotechnology. Numerous nanomaterials, including liposomes, dendrimers, micelles, exosomes, and gold nanoparticles, are developed and used. Distinctive characteristics of mentioned nanocarriers are discussed along with strategies that can be employed for enhancing the delivery of drugs to colorectal cancer cells. The review also quotes the most relevant preclinical and clinical studies that show how these nanomaterials improve drug solubility, stability, and targeted delivery while overcoming the shortcomings of conventional therapies. Nanotechnology has made CRC treatment very efficient and advanced, which has opened up new possibilities for targeted drug delivery. Preclinical and clinical studies have also proved that the use of nano-formulations in colon-specific delivery systems have significant results, indicating potential for better patient outcomes. Future research can be done in order to overcome the hurdles regarding biocompatibility, expansion, and regulatory challenges. Large-scale clinical trials and nanomaterial formulation optimization should be the main goals of future research to confirm the efficacy and safety of these novel treatments.

The RNA-binding protein hnRNPA2B1 acts as an m6A reader and plays a role in tumor development. This study investigates the potential mechanism of hnRNPA2B1 in colorectal cancer (CRC) progression. The expression profiles of hnRNPA2B1, circCDYL, and PHF8 in CRC cell lines were analyzed. Following si-hnRNPA2B1 transfection, CRC cell proliferation, invasion, and migration were evaluated by CCK-8 and Transwell. CDYL expression was detected after actinomycin D and RNase R treatment. RIP was conducted to assess the enrichment of hnRNPA2B1 and m6A on circCDYL. RIP and RNA pull-down assays established the interaction between circCDYL and EIF4A3/PHF8. EIF4A3 expression was evaluated using RT-qPCR and Western blot techniques. hnRNPA2B1 and PHF8 displayed high expression levels, whereas circCDYL showed low expression levels in colorectal cancer cells. Inhibition of hnRNPA2B1 reduced CRC cell proliferation, migration, and invasion. hnRNPA2B1 mechanistically elevated the m6A level of circCDYL while decreasing its expression, which in turn reduced the binding of circCDYL to EIF4A3 and enhanced PHF8 expression. In summary, hnRNPA2B1-mediated m6A modification decreases circCDYL expression, which inhibits the interaction of circCDYL with EIF4A3, enhances PHF8 expression, and ultimately facilitates CRC progression.

Precision medicine has revolutionized the treatment of colorectal cancer by enabling a personalized approach tailored to each patient's unique genetic characteristics. Genomic profiling allows for the identification of specific mutations in genes such as KRAS, BRAF, and PIK3CA, which play a crucial role in cell signaling pathways that regulate cell proliferation, apoptosis, and differentiation. This information enables doctors to select targeted therapies that inhibit specific molecular pathways, maximizing treatment effectiveness and minimizing side effects. Precision medicine also facilitates adaptive monitoring of tumor progression, allowing for adjustments in therapy to maintain treatment effectiveness. While challenges such as high costs, limited access to genomic technology, and the need for more representative genomic data for diverse populations remain, collaboration between researchers, medical practitioners, policymakers, and the pharmaceutical industry is crucial to ensure that precision medicine becomes a standard of care accessible to all. With continued advances and support, precision medicine has the potential to improve treatment outcomes, reduce morbidity and mortality rates, and enhance the quality of life for colorectal cancer patients worldwide.

Colorectal cancer (CRC) is one of the deadliest neoplasia. Intrinsic or acquired resistance is the main cause of failure of therapy regimens that leads to relapse and death in CRC patients. The widely used chemotherapeutic agent 5-fluorouracil (5-FU) remains the mainstay for therapeutic combinations. Unfortunately, chemotherapeutic resistance and side effects are frequent events that compromise the success of these therapies; the dysregulation of enzymes that regulate 5-FU metabolism increases the expression and activity of efflux pumps. Additional tumor cell adaptations such as epithelial-mesenchymal transition (EMT), autophagy shaping of the tumor microenvironment, and inflammation contribute to chemoresistance. Finding new strategies and alternatives to enhance conventional chemotherapies has become necessary. Recently, the study of natural compounds has been gaining strength as an alternative to chemotherapeutics in different cancers. Curcumin, trimethylglycine, resveratrol, artemisinin, and some helminth-derived molecules, among others, are some natural compounds studied in the context of CRC. This review discusses the main benefits, mechanisms, advances, and dark side of conventional chemotherapeutics currently evaluated in CRC treatment. We also analyzed the landscape of alternative non-conventional compounds and their underlying mechanisms of action, which could, in the short term, provide fundamental knowledge to harness their anti-tumor effects and allow them to be used as alternative adjuvant therapies.

Altered levels of reactive oxygen species (ROS) are recognized as one of the key factors in mediating tumor cell survival in the tissue microenvironment, where they play a role in the initiation, progression and recurrence/relapse of colorectal cancer (CRC). Tumor cells can adapt to oxidative stress (OS) using genetic or metabolic reprogramming in the long or short term. In addition, tumor cells defend themselves through positive regulation of antioxidant molecules, enhancing ROS-driven proliferation. Balanced oxidative eustress levels can influence chemotherapy resistance, allowing tumor cells to survive treatment. Secondary effects of chemotherapy include increased ROS production and redox stress, which can kill cancer cells and eliminate drug resistance. Anticancer treatments based on manipulating ROS levels could represent the gold standard in CRC therapy. Therefore, exploring the modulation of the response to OS in deregulated signaling pathways may lead to the development of new personalized CRC treatments to overcome therapy resistance. In this review, we explore the role of ROS in the initiation and progression of CRC and their diagnostic implications as biomarkers of disease. Furthermore, we focused on the involvement of ROS in different CRC therapeutic options, such as surgery, radiotherapy, theranostic imaging, chemotherapy and immunotherapy and other precision medicine approaches.

Nitrogen mustard (NM) is a vesicant agent with potent toxic effects on various tissues. Numerous theories have been proposed to explain its toxic mechanisms, yet research on the interconnections among these theories is lacking. This study focuses on analyzing the characteristics of genes involved in NM-induced bronchial injury within the Comparative Toxicogenomics Database (CTD). Subsequently, based on the CTD, we compared and analyzed the acute exposure and delayed changes following exposure in 16HBE cells. The injury processes caused by NM to bronchial and skin tissues are similar, primarily involving metabolism and regulation of nuclear constituents and inflammatory responses within the cellular matrix. During the acute exposure phase, NM rapidly induces nuclear stress, with the JUN family at the core of regulating metabolic and nucleic acid activities, and various nuclear binding proteins exhibit abnormalities. Delayed reactions following acute exposure are primarily centered in the cytoplasmic region, with diverse reaction types, including oxidative stress and responses to exogenous stimuli. Abnormalities in the activity of multiple cellular matrix enzymes are observed, with a relatively even involvement of various stress responses. Communication between the nucleus and cytoplasm is extreme active during the injury, and the content of the communication changes over time. These results suggest a temporal sequence in which NM causes chromatin damage and mediates cytoplasmic stress responses. In prevention and first aid, rapid DNA repair should be the primary focus, while subsequent treatment after acute exposure should focus more on delayed inflammatory and oxidative stress responses.

Gastrointestinal (GI) cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and esophageal cancer, pose a significant medical and economic burden globally, accounting for the majority of new cancer cases and deaths each year. A lack of knowledge about the molecular mechanisms of GI cancers is reflected in the low efficacy of treatment for individuals with late stage and recurring illness. Understanding the molecular pathways that promote the growth of GI cancers may open doors for their therapy. Numerous long non-coding RNAs (lncRNAs) that are produced differently in normal and malignant tissues have been discovered by genome-wide techniques. The role of lncRNAs in the diagnosis, proliferation, metastasis, and drug resistance of different GI cancers has been investigated in recent research. LncRNAs may affect transcription, epigenetic modifications, protein/RNA stability, translation, and post-translational modifications via their interactions with DNA, RNAs, and proteins. Also, by functioning as competing endogenous RNAs (ceRNAs), they control the synthesis of certain microRNAs (miRNAs), which in turn modify the downstream target molecules of these miRNAs. Based on recent studies, lncRNAs in particular, CRNDE and HOTAIR, sponge different miRNAs and their downstream genes, which in turn regulate GI cancers development, including cell proliferation, invasion, migration, and chemoresistance. In this comprehensive review, we present an overview of the biological roles of CRNDE and HOTAIR and their associated mechanisms, miRNAs/mRNA pathways, in various GI cancers, encompassing colorectal cancer, hepatocellular carcinoma, esophageal cancer, and gastric cancer.

The Wnt signaling pathway is critical in the onset and progression of gastrointestinal (GI) cancers. Anomalies in this pathway, often stemming from mutations in critical components such as adenomatous polyposis coli (APC) or β-catenin, lead to uncontrolled cell proliferation and survival. In the case of colorectal cancer, dysregulation of the Wnt pathway drives tumor initiation and growth. Similarly, aberrant Wnt signaling contributes to tumor development, metastasis, and resistance to therapy in other GI cancers, such as gastric, pancreatic, and hepatocellular carcinomas. Targeting the Wnt pathway or its downstream effectors has emerged as a promising therapeutic strategy for combating these highly aggressive GI malignancies. Here, we review the dysregulation of the Wnt signaling pathway in the pathogenesis of GI cancers and further explore the therapeutic potential of targeting the various components of the Wnt pathway. Furthermore, we summarize and integrate the preclinical evidence supporting the therapeutic efficacy of potent Wnt pathway inhibitors with completed and ongoing clinical trials in GI cancers. Additionally, we discuss the challenges of Wnt pathway-targeted therapies in GI cancers to overcome these concerns for effective clinical translation.

In this study, we aimed to investigate the molecular mechanism of Krüppel-like factor 7 (KLF7) in colorectal cancer (CRC) cell invasion and migration. The expression pattern of KLF7 in CRC tissues and the correlation between KLF7 expression and clinical symptoms of CRC were analyzed. CRC cell lines were transfected with si-KLF7, followed by qRT-PCR or western blot detection of KLF7, miR-139-5p, and tumor protein D52 (TPD52) expression, cell counting kit-8 (CCK-8) assay to detect cell viability, and transwell detection of invasion and migration. Chromatin immunoprecipitation (ChIP) analyzed the enrichment KLF7 in the miR-139-5p promoter. The dual-luciferase reporter assay verified the binding relationship between KLF7 and miR-139-5p, and between miR-139-5p and TPD52. In the subcutaneous tumorigenesis experiment, tumor growth was observed and ki67-positive expression was detected. KLF7 is abundantly expressed in CRC cells KLF7 silencing inhibits CRC cell viability, invasion, and migration. KLF7 represses miR-139-5p expression by binding to the miR-139-5p promoter. miR-139-5p targets TPD52 expression. miR-13-5p inhibition or TPD52 overexpression partially counteracted the effect of KLF7 silencing in CRC cells. KLF7 silencing suppresses tumor growth in vivo. In conclusion, KLF7 suppresses miR-139-5p expression by binding to the miR-139-5p promoter, thereby upregulating TPD52 expression and enhancing CRC cell invasion and migration.

Colorectal cancer (CRC) continues to be a global health concern, necessitating further research into its complex biology and innovative treatment approaches. The etiology, pathogenesis, diagnosis, and treatment of colorectal cancer are summarized in this thorough review along with recent developments. The multifactorial nature of colorectal cancer is examined, including genetic predispositions, environmental factors, and lifestyle decisions. The focus is on deciphering the complex interactions between signaling pathways such as Wnt/β-catenin, MAPK, TGF-β as well as PI3K/AKT that participate in the onset, growth, and metastasis of CRC. There is a discussion of various diagnostic modalities that span from traditional colonoscopy to sophisticated molecular techniques like liquid biopsy and radiomics, emphasizing their functions in early identification, prognostication, and treatment stratification. The potential of artificial intelligence as well as machine learning algorithms in improving accuracy as well as efficiency in colorectal cancer diagnosis and management is also explored. Regarding therapy, the review provides a thorough overview of well-known treatments like radiation, chemotherapy, and surgery as well as delves into the newly-emerging areas of targeted therapies as well as immunotherapies. Immune checkpoint inhibitors as well as other molecularly targeted treatments, such as anti-epidermal growth factor receptor (anti-EGFR) as well as anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies, show promise in improving the prognosis of colorectal cancer patients, in particular, those suffering from metastatic disease. This review focuses on giving readers a thorough understanding of colorectal cancer by considering its complexities, the present status of treatment, and potential future paths for therapeutic interventions. Through unraveling the intricate web of this disease, we can develop a more tailored and effective approach to treating CRC.

This study aims to explore the potential targets and anticancer mechanisms of dendrobine from Dendrobium nobile in the treatment of colorectal cancer through network pharmacology, and to experimentally validate its specific effects.

Initially, potential targets of dendrobine were identified using the ITCM Traditional Chinese Medicine database, while colorectal cancer-related genes were obtained from the NCBI Gene database, with the intersection of these datasets taken for further analysis. Functional enrichment analysis was conducted using the Metascape database, and a protein-protein interaction (PPI) network was constructed. Additionally, cell culture, cell proliferation assays, and wound healing assays were performed. The Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways were analyzed using PCR and Western blot experiments.

The PPI network constructed from 152 intersecting genes revealed that these genes play crucial roles in processes such as cell proliferation, apoptosis, and signal transduction. Cell-based assays demonstrated that dendrobine significantly inhibits the proliferation and migration of colorectal cancer cells. Furthermore, PCR and Western blot results indicated that dendrobine suppresses colorectal cancer cell proliferation and migration by modulating the Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways.

Dendrobine exhibits significant anticancer potential against colorectal cancer by regulating the Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways, providing a theoretical foundation and experimental evidence for its therapeutic application in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.

We utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, in vitro experiments were performed on DLX2, a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.

Eight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 FXYD5+ tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 FXYD5+ tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. In vitro experiments confirmed DLX2 as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.

In summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.

Colorectal cancer (CRC) is highly prevalent worldwide, with more patients experiencing colorectal cancer liver metastases (CRLM). This study aimed to identify key genes in CRLM through single-cell sequencing data reanalysis and experimental validation.

The study analyzed single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for gene functional enrichment analysis. The Cancer Genome Atlas (TCGA) data enabled bulk-RNA expression and survival prognosis analysis. Real-time polymerase chain reaction (qPCR) detected mRNA expression, whereas Western blot determined protein levels. Cell function experiments assessed SPARC's impact on CRC cell behavior.

Cluster analysis showed 23 classes among 17 CRLM samples, representing six cell types. A GO and KEGG analysis identified interleukin-1 beta (IL1B), CD2 molecule (CD2), and C-X-C motif chemokine ligand 8 (CXCL8) as significant prognostic factors in CRC. Secreted protein acidic and cysteine rich (SPARC) was one of the top differentially expressed genes (DEGs) in tissue stem cells, confirmed in primary and metastatic lesions. Metastatic lesions showed higher expression of SPARC and CRC stem cell marker leucine-rich repeat containing G protein-coupled receptor 5 (LGR5), which was significantly correlated positively with LGR5 expression. Knockdown of SPARC reduced CRC cell sphere- and colony-formation, invasion, and migration abilities. Overexpression of SPARC significantly increased the malignancy of CRC cells.

Several key genes were identified in the process of CRLM. In CRLM samples and those corresponding to CRC stem cells, SPARC was significantly upregulated. In the therapy of CRLM, SPARC might be a potential target.

WNT3A is an intestinal ligand triggering the Wnt/β-catenin (Wnt) pathway, which can be enhanced by R-spondin 1 (RSPO1) through the RSPO1-LGR axis or antagonized by the adenomatous polyposis coli (APC) protein supporting β-catenin-degradation. Wnt interplays with several pathways including PI3K/mTOR (mTOR). In this study, we evaluated the influence of WNT3A-commercial and home-made culture media and RSPO1 protein on the Wnt and mTOR interplay in non-APC and APC-mutated intestinal patient-derived organoids (PDOs). Normal mucosa (NM) of sporadic CRC and FAP PDOs were cultured with: WNT3A-lacking/containing commercial (A/A+B) or home-made (BASAL/WNT3A-conditioned medium (CM)±RSPO1) media. In non-APC-mutated-PDOs (CRC-NM), WNT3A-CM, over commercial A+B, strongly activated Wnt-target-genes CCND1 and c-MYC. Most importantly, the addition of RSPO1 to home-made WNT3A-CM or A+B led to the downregulation of the mTOR-downstream-effector phospho-S6 ribosomal protein (p-S6R), highlighting the activation of the RSPO1-pS6R in both non-APC (CRC-NM) and APC-mutated (FAP-NM) PDOs, independently from LGR5 gene expression modulation. Our work demonstrates that home-made WNT3A-CM strongly impacts the crosstalk between Wnt and mTOR over commercial media, and proposes RSPO1 as a key regulator of the RSPO1-p-S6R axis in both non-APC and APC-mutated PDOs. Together, these findings represent an important methodological guide for scientists working in these fields to select the most appropriate intestinal PDO media.

One of the critical challenges in managing colorectal cancer (CRC) is the development of oxaliplatin (OXP) resistance. Long non-coding RNAs (lncRNAs) have a crucial role in CRC progression and chemotherapy resistance, with exosomal lncRNAs emerging as potential biomarkers. This study aimed to predict key lncRNAs involved in OXP-resistance using in-silico methods and validate them using RT-qPCR methods in CRC cells and their isolated exosomes. Two public datasets, GSE42387 and GSE119481, were downloaded from the GEO database to identify differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) associated with OXP-resistance in the HCT116 cell line. The analysis of GSE42387 revealed 210 DEGs, and GSE119481 identified 73 DEmiRNAs. A protein-protein interaction (PPI) network analysis of the DEGs identified 133 interconnected genes, from which the top ten genes with the highest degree scores were selected. By intersecting predicted miRNAs targeting these genes with the DEmiRNAs, 38 common miRNAs were found. Subsequently, 224 lncRNAs targeting these common miRNAs were predicted. LncRNA-miRNA-mRNA network were constructed and the top five lncRNAs with the highest degree scores were identified. Analysis using the Kaplan-Meier plotter database revealed that the key lncRNAs NEAT1, OIP5-AS1, and MALAT1 are significantly associated with the overall survival of CRC patients. To validate these lncRNAs, OXP-resistant HCT116 sub-cell line (HCT116/OXR) was developed by exposing parental HCT116 cells to gradually increasing concentrations of OXP. Exosomes derived from both HCT116 and HCT116/OXR cells were isolated and characterized utilizing dynamic light scattering (DLS), transmission electron microscopy (TEM), and Western blotting. RT-qPCR confirmed elevated levels of NEAT1, OIP5-AS1, and MALAT1 in HCT116/OXR cells and their exosomes compared to parental HCT116 cells and their exosomes. This study concludes that NEAT1, OIP5-AS1, and MALAT1 are associated with the OXP-resistance in CRC. The high levels of these lncRNAs in exosomes of resistant cells suggest their involvement in intercellular communication and resistance propagation. This positioning makes them promising biomarkers for OXP-resistance in CRC.

This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.

Patient-derived xenograft (PDX) models are widely acknowledged for their ability to reflect the heterogeneity of human cancers and can be used to improve preclinical models. In this study, we evaluated the factors affecting the tumor formation rate of the PDX colorectal cancer (CRC) model and conducted preliminary drug sensitivity tests.

CRC patients who underwent elective surgery at Shaoxing People's Hospital from November 2019 to October 2020 were included. The tumor tissue obtained from surgery was transplanted to the back of NSG mice, and the PDX model was established and subcultured to the F3 generation. Factors that affected tumorigenicity were analyzed and compared histologically. Drug interventions included 5-fluorouracil, oxaliplatin, and propofol.

Sixty CRC patients were included in this study, and tumorigenesis was observed in CRC tissue derived from 37 cases (62%). The primary tumor malignancy degree (tumor stage and degree of cell differentiation), preoperative carcinoembryonic antigen level, and tumor location in CRC patients could affect the tumorigenicity of the PDX model. Histopathological analysis of CRC-PDX transplanted tumor tissue was highly consistent with the patient's tumor tissue. All four chemotherapy regimens could inhibit tumor growth and cause tumor tissue damage. Propofol could inhibit diarrhea in mice and protect intestinal mucosa.

The CRC-PDX model established in this study can maintain the biological characteristics of primary tumors and can be used as a reference model for the individualized treatment of CRC patients. The degree of malignancy of the primary tumor is the primary factor affecting the tumorigenesis rate of the PDX model.

The metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI.

Genes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein-protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription-quantitative real-time PCR (RT-qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes.

This study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune-related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells.

We distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI.

Colorectal cancer (CRC) poses a significant global health challenge, characterized by substantial prevalence variations across regions. This study delves into the therapeutic potential of rutin, a polyphenol abundant in fruits, for treating CRC. The primary objectives encompass identifying molecular targets and pathways influenced by rutin through an integrated approach combining bioinformatic analysis and experimental validation. Employing Gene Set Enrichment Analysis (GSEA), the study focused on identifying potential differentially expressed genes (DEGs) associated with CRC, specifically those involved in regulating reactive oxygen species, metabolic reprogramming, cell cycle regulation, and apoptosis. Utilizing diverse databases such as GEO2R, CTD, and Gene Cards, the investigation revealed a set of 16 targets. A pharmacological network analysis was subsequently conducted using STITCH and Cytoscape, pinpointing six highly upregulated genes within the rutin network, including TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Gene Ontology (GO) analysis predicted functional categories, shedding light on rutin's potential impact on antioxidant properties. KEGG pathway analysis enriched crucial pathways like metabolic and ROS signaling pathways, HIF1a, and mTOR signaling. Diagnostic assessments were performed using UALCAN and GEPIA databases, evaluating mRNA expression levels and overall survival for the identified targets. Molecular docking studies confirmed robust binding associations between rutin and biomolecules such as TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Experimental validation included inhibiting colorectal cell HT-29 growth and promoting cell growth with NAC through MTT assay. Flow cytometric analysis also observed rutin-induced G1 phase arrest and cell death in HT-29 cells. RT-PCR demonstrated reduced expression levels of target biomolecules in HT-29 cells treated with rutin. This comprehensive study underscores rutin's potential as a promising therapeutic avenue for CRC, combining computational insights with robust experimental evidence to provide a holistic understanding of its efficacy.

Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC.

PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger's and Begg's tests.

Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = -30.17, 95 % CI [-41.10, -19.23], P < 0.001) and Shannon index (WMD = -0.11 95 % CI [-0.18, -0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = -0.07 95 % CI [-0.12, -0.03], P = 0.003), Bifidobacteria (WMD = -0.03 95 % CI [-0.05, -0.01], P = 0.016), and Klebsiella (WMD = -0.01 95 % CI [-0.01, -0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = -0.04 95 % CI [-0.07, -0.02], P = 0.002), Peptostreptococcaceae (WMD = -0.03 95 % CI [-0.05, -0.00], P = 0.021), Lachnospiraceae (WMD = -0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = -0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = -0.01 95 % CI [-0.02, -0.01], P = 0.001), and Lachnoclostridium (WMD = -0.02 95 % CI [-0.03, -0.00], P = 0.040) was decreased in the CRC group, while Proteobacteria (WMD = 0.04 95 % CI [0.02,0.05], P < 0.001) was increased.

The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.