Colon Cancer Research Articles

The role of celastrol in inflammation and diseases.

Celastrol is one of the main active ingredients extracted from the plant Tripterygium wilfordii Hook F. A growing number of studies have shown that celastrol has various pharmacological effects, including anti-inflammation, anti-rheumatism, treatment of neurodegenerative diseases, and anti-tumor. This article systematically summarized the mechanism and role of celastrol in lipid metabolism and obesity, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, inflammatory bowel disease, neurodegenerative diseases, and cancer and other diseases (such as diabetes, respiratory-related diseases, atherosclerosis, psoriasis, hearing loss, etc.). The celastrol played roles in inflammation response, cell apoptosis, autophagy, ferroptosis, and lipid metabolism mainly by acting on chondrocytes, macrophages, mitochondria, and endoplasmic reticulum (ER) through NF-κB, STAT, MAPK, TLR, PI3K-AKT-mTOR, and other signal pathways. This review could provide a reference for the clinical application and further development and utilization of celastrol.

Outcomes of Colectomy for Nonmalignant Polyps and Colon Cancer: A Propensity Score-Matched Analysis.

In the United States, while most nonmalignant polyps are effectively treated through endoscopic removal, colectomy remains a treatment option for selected cases of nonmalignant polyps (NMPs) and colon cancer. This study aimed to compare postoperative outcomes for colectomies in these two conditions, hypothesizing similar complication rates. We conducted a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database from 2015 to 2021, including patients who underwent elective colectomies for colon cancer or NMPs. Using a 2:1 propensity score matching for demographics, American Society of Anesthesiologists classification, surgical methods, and comorbidities, we evaluated outcomes such as 30-d mortality, complications, anastomotic leakage, and hospital stay duration. A total of 47,960 patients, including 30,549 colon cancer patients and 17,411 NMP patients, were included after propensity score matching analysis. We concluded that there was no significant difference in mortality and reoperation rates which were 0.6% and 3.3% in patients undergoing colectomy with colon cancer, compared to 0.5% and 3.1% in those with NMP, respectively [P=0.64, P=0.21,]. In addition, the anastomotic leak rates were remarkably similar in both the colon cancer (2.4%) and NMP (2.2%) groups. [P=0.13]. Most of the 30-d postoperative surgical complications, such as sepsis, septic shock, wound disruption, and urinary tract infection exhibited similar incidence rates, however, some of them, such as readmission, pulmonary embolism, and length of stay, varied between the groups. Our findings underscore the similar postoperative outcomes between colon cancer and NMP groups, advocating for consideration of advanced endoscopic techniques for NMPs to potentially enhance patient care and outcomes.

Dysfunctional mitochondrial bioenergetics sustains drug resistance in cancer cells.

Resistance to drugs is one of the major issues affecting the response to pharmacological treatments for tumors. Different mechanisms have been proposed to explain the development of cancer drug resistance (CDR), and several approaches to overcome it have been suggested. However, the biological basis of CDR remains unclear. Here, we investigated whether mitochondrial damage and consequent mitochondrial dysfunction are major causes of drug resistance in different tumors. To this end, we used cell lines from three tumors: hepatocellular carcinoma, breast cancer, and colon cancer. We then applied a protocol that recapitulates chemotherapy regimens in patients, rendering each cell line resistant to the drug commonly used in their respective treatments. The combination of cellular respiration analysis, gene expression analysis of cytochrome c oxidase isoforms, and mass spectrometry assessment of cardiolipin reveals that mitochondrial dysfunction is the underlying cause of the resistant phenotype. Importantly, we disclosed for the first time the rapid inhibition of oxidative phosphorylation (OXPHOS) by L-lactate, the major product of fermentation. Finally, we demonstrated that inhibition of lactic acid fermentation and activation of OXPHOS can increase drug sensitivity in all tested drug-resistant cancer cells. Taken together, our results suggest that inhibiting fermentation and enhancing mitochondrial function in cancer cells may be a concrete option to control the worrisome phenomenon of CDR.

Endoplasmic Reticulum-Targeted Polymer-Manganese Nanocomplexes for Tumor Immunotherapy.

Manganese ions (Mn2+) are an immune activator that enhances the activation of both cGAS and STING proteins. The STING signaling activation and subsequential immune responses are predominantly associated with endoplasmic reticulum (ER). Therefore, ER targeting of Mn2+ in the subcellular compartments would promote the activation of STING signaling pathways. Herein, we report the design of ER-targeted manganese-based nanocomplexes (NCs) by complexation of Mn2+ with a zwitterionic polymer, poly[2-(N-oxide-N,N-dimethylamino) ethyl methacrylate] (OPDMA). The Mn/OPDMA nanocomplexes (Mn/OPDMA NCs) keep a long blood circulation for tumor accumulation and trigger adsorption-mediated transcytosis for extravasation and deep tumor penetration. Notably, in the tumor-associated macrophages, the Mn/OPDMA NCs can preferentially translocate to their ERs, significantly enhancing cGAS-STING pathway activation for tumor-associated macrophage polarization and IFN-β secretion. In mouse colon and hepatocellular cancer models, the intravenously administrated Mn/OPDMA NCs efficiently remodel tumor immune microenvironment, greatly retard tumor growths by 2.4- to 5-fold, and prolong the mouse survivals compared to free Mn2+-treated mice. This study provides the ER-targeted delivery of Mn2+ that achieves robust STING activation and, thus, potent systemic tumor inhibition without the toxicity of free Mn2+.

Potential prognostic and predictive biomarkers: METTL5, METTL7A, and METTL7B expression in gastrointestinal cancers.

The methyltransferase gene family is known for its diverse biological functions and critical role in tumorigenesis. This study aimed to identify these family genes in common gastrointestinal (GI) cancers using comprehensive methodologies. Gene identification involved analysis of scientific literature and insights from The Cancer Genome Atlas (TCGA) database. RNA sequencing (RNA-seq) data for colon, gastric, pancreatic, esophageal, and liver cancers were collected, processed, and normalized. Differential expression analysis was conducted using R software with the Limma package. Additionally, real-time PCR analysis was performed on 30 tumor and 30 normal tissue samples from patients with colon and gastric cancer. Pathway analysis was conducted via the EnrichR web tool, while survival analysis used Cox regression methods, and biomarker potential was assessed with the pROC package. Prognostic significance was evaluated by examining associations between gene expression, patient survival, and recurrence rates. The study also investigated diagnostic potential through receiver operating characteristic (ROC) analysis, and assessed how small molecules affect gene expression, with implications for drug resistance and sensitivity, analyzed via CCLE and GDSC datasets. Findings revealed METTL5 overexpression in colon, liver, esophagus, and pancreas cancers, while METTL7A was underexpressed in gastric, esophagus, liver, and colon cancers. METTL7B expression varied, being higher in gastric and esophagus cancers but lower in liver and colon cancers. Enrichment analysis identified pathways related to these genes, and survival analysis associated altered METTL7A and METTL5 expressions with poor prognosis and higher recurrence rates. These findings suggest that METTL genes could serve as predictive biomarkers in GI cancers, offering potential implications for patient prognosis and treatment response.

Risk of Lymph Node Metastasis in T2 Colon Cancer: A Nationwide Population-Based Cohort Study.

Similar to T1 colon cancer (CC), risk stratification may guide T2 CC treatment and reduce unnecessary major surgery. In this study, prediction models were developed that could identify T2 CC patients with a lower risk of lymph node metastasis (LNM) for whom (intensive) follow-up after local treatment could be considered. A nationwide cohort study was performed involving pT2 CC patients who underwent surgery between 2012 and 2020, using data from the Dutch ColoRectal Audit, which were linked to the Nationwide Pathology Databank. Four machine learning models were evaluated to predict LNM. LNMs were found in 1877/9803 patients (19.1%). Independent risk factors included (younger) age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.979-0.990), left-sided CC (OR 1.5, 95% CI 1.4-1.7), poor differentiation (OR 1.7, 95% CI 1.4-2.2), and lymphovascular invasion (LVI; OR 4.1, 95% CI 3.6-4.7). A deficient mismatch repair (MMR) status significantly lowered the risk of LNM (OR 0.3, 95% CI 0.2-0.5). The general linear model demonstrated the highest prediction accuracy, achieving area under the receiver operating characteristic curves of 0.67 and 0.68, with good calibration. In the absence of risk factors, elderly patients (≥74years of age) had a predicted risk of LNM of 10.7%, yet up to 30% experienced postoperative complications, with mortality rates reaching up to 3.5%. Patients with a deficient MMR status had a predicted risk of LNM of 6.1% if LVI was absent and the tumor was well-differentiated. The risk of LNM should be weighed against surgical risks. The findings of this study will enable clinicians to make more deliberate considerations about these competing risks before making a shared decision.

IKZF1 promotes pyroptosis and prevents M2 macrophage polarization by inhibiting JAK2/STAT5 pathway in colon cancer.

Pyroptosis and macrophage pro-inflammatory activation play an important role in hepatocellular carcinoma (HCC) progression. However, the specific regulatory mechanisms remain unclear. We identified pyroptosis-related differentially expressed genes (DEGs) based on the GSE4183 and GSE44861 datasets as well as EVenn database. Expression levels of key genes were detected by qRT-PCR. IKZF1 was overexpressed in colon cancer cells and tumor-bearing mice, and its functions were assessed by various cell biology assays in vitro and in vivo. To investigate the interactions between IKZF1 and macrophages, a co-culture system was constructed. The activator RO8191 or inhibitor ruxolitinib of the JAK/STAT pathway was employed to confirm whether IKZF1 inhibited colon cancer development by regulating JAK2/STAT5 pathway. Pyroptosis-related hub genes RBBP7, HSP90AB1, and RBBP4 were highly expressed, while IKZF1, NLRP1, and PYCARD were lowly expressed. These hub genes had good performance in distinguishing colon cancer from controls. Furthermore, overexpression of IKZF1 inhibited tumor growth and promoted pyroptosis. Overexpression of IKZF1 suppressed cell proliferation, metastasis, and inactivated JAK2/STAT5 signaling pathway in colon cancer cells. Furthermore, upregulation of IKZF1 promoted M1 macrophage polarization while inhibiting M2 macrophage polarization in vivo and in vitro by inhibiting the JAK2/STAT5 signaling pathway. This study identifies IKZF1 as a potential biomarker inactivating JAK2/STAT5 pathway for colon cancer.

Implementation of the Box-Behnken Design in the Development and Optimization of Methotrexate-Loaded Microsponges for Colon Cancer.

Methotrexate (MTX) is an effective anticancer agent with limited water solubility, resulting in lower absorption in the gastrointestinal tract when administered orally. The present aim of the study is to construct sustained-release formulation of MTX-loaded microsponges with enhanced intestinal absorption and bioavailability using a quasi-emulsion solvent diffusion method. The Box-Behnken design (BBD) was adopted for this purpose. Particle size, encapsulation efficiency (EE), Q 2 h % (% drug release in 2 h), and Q 24 h % (% drug release in 24 h) were used as dependent factors, and polyvinyl alcohol, solvent, and stirring speed were used as independent factors. The prepared microsponges were characterized to assess their particle size and encapsulation efficacy (%). Attenuated total reflectance-Fourier transform infrared spectroscopy and differential scanning calorimetry were used to verify the compatibility study. Moreover, the cytotoxicity study was conducted on the HT-29 cell line. The optimized formulation exhibited a % encapsulation efficacy of 87.191% and a particle size of 2.176 µm. Furthermore, the optimized formulation demonstrated sustained drug release (85.71%) in Simulated Gastric Fluid (SGF) fluid at different pHs 1.2, 6.8, and 7.4. The stability study of the optimized formulation revealed good stability in terms of drug release, % encapsulation efficacy, and particle size. The results of the optimized formulation demonstrated that the viability of HT-29 colon cancer (CC) cells was dose-dependently decreased by MTX-loaded microsponges. BBD was successfully employed for the development and optimization of MTX microsponges filled in Eudragit S-100-coated hard gelatin capsule, depicting their potential release of MTX from microsponges capsule only at the colonic region and found to be potential carrier system for CC.

Factor analysis of postsurgical gastroparesis syndrome after right hemicolectomy for colon cancer

Factor analysis of postsurgical gastroparesis syndrome after right hemicolectomy for colon cancer

ASO Visual Abstract: Neoadjuvant Immunotherapy Followed by Surgery Compared with Upfront Surgery Alone in Operable Colon Cancer with Deficient Mismatch Repair-Modelling Oncological Outcomes and Numbers Needed to Treat.

ASO Visual Abstract: Neoadjuvant Immunotherapy Followed by Surgery Compared with Upfront Surgery Alone in Operable Colon Cancer with Deficient Mismatch Repair-Modelling Oncological Outcomes and Numbers Needed to Treat.

Expression, characterization and anti-colon cancer activity of recombinant ginseng peptides with amino acid tandem repeats.

Ginseng peptides, small molecule active ingredients in ginseng, are mainly extracted naturally or synthesised chemically, but high costs and difficulties hinder further research. In this study, a ginseng hexapeptide FKEHGY, named antitumor peptide 0601 (AT0601) and its five tandem sequence repeats AT0605, were expressed in Bacillus subtilis WB600 for the first time, and the bioactivity study showed that the anticancer activity of AT0605 was even significantly higher than that of AT0601 for colon cancer CT26 cells, with IC50s of 16.82±1.3 μM (48 h) and 855.57±6.04 μM (48 h), respectively, i.e. AT0605 achieves the same inhibition rate for CT26 cells at a concentration 50 times lower than that of AT0601. Similar to the ginseng peptide AT0601, recombinant AT0605 also inhibited cell growth by blocking cells in the G1 phase and activated the mitochondria-associated caspase pathway to induce apoptosis. In conclusion, all two kinds of the recombinant ginseng peptides could also inhibit cell proliferation through mechanisms such as inhibiting cell cycle arrest and inducing a decrease in mitochondrial membrane potential.

Impact of surgical specialization on long-term survival after emergent colon cancer resections.

The impact of surgical specialization on long-term survival in patients undergoing emergent colon cancer resections remains unclear. A retrospective analysis was conducted on all patients who underwent emergent colon cancer resections at a secondary care hospital between 2010 and 2020. The most senior surgeon performing the procedures was classified as colorectal surgeon (CS) or non-colorectal surgeon (NCS). NCS was further divided into acute care surgeons (ACSs) or general surgeons (GSs). Overall survival (OS) and cancer-free survival (CFS) were compared in patients operated by surgeons with different specializations. A total of 235 emergent resections were performed during the study period, of which 99 (42%) were performed by CS and 136 (58%) by NCS. In adjusted Cox regression analyses, OS and CFS were similar in patients operated on by CS and NCS (hazard ratio (HR) for OS: 1.02 (0.72-1.496), p = 0.899 and HR for CFS: 0.91 (0.61-1.397), p = 0.660). Similarly, OS and CFS were equivalent in patients operated by ACS and CS (HR for OS: 1.10 (0.75-1.62), p = 0.629 and HR for CFS: 1.24 (0.80-1.92), p = 0.343). However, patients operated by GS had significantly shorter OS and CFS (HR for OS: 1.78 (1.05-3.00), p = 0.031 and HR for CFS: 1.83 (1.02-3.26), p = 0.041) compared with those operated by ACS and CS. Long-term survival after emergent colon cancer resections was similar in patients operated on by CS and NCS, and the subgroup of ACS, indicating equivalent comparable surgical quality. The less favorable poorer survival observed for patients operated on by GS may possibly be due to less frequent exposure to colorectal and emergent surgery.

Amphiphilic Polyaspartamide Derivatives with Cholesterol Introduction Enhanced Ex Vivo mRNA Transfection Efficiency to Natural Killer Cells.

Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its ex vivo delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the α-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the ex vivo engineering of NK cells.

Attractor Landscape Analysis Reveals a Reversion Switch in the Transition of Colorectal Tumorigenesis.

A cell fate change such as tumorigenesis incurs critical transition. It remains a longstanding challenge whether the underlying mechanism can be unraveled and a molecular switch that can reverse such transition is found. Here a systems framework, REVERT, is presented with which can reconstruct the core molecular regulatory network model and a reversion switch based on single-cell transcriptome data over the transition process is identified. The usefulness of REVERT is demonstrated by applying it to single-cell transcriptome of patient-derived matched organoids of colon cancer and normal colon. REVERT is a generic framework that can be applied to investigate various cell fate transition phenomena.

Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth.

Colorectal cancer (CRC) usually creates an immunosuppressive microenvironment, thereby hindering immunotherapy response. Effective treatment options remain elusive. Using scRNA-seq analysis in a tumor-bearing murine model, it is found that lobeline, an alkaloid from the herbal medicine lobelia, promotes polarization of tumor-associated macrophages (TAMs) toward M1-like TAMs while inhibiting their polarization toward M2-like TAMs. Additionally, lobeline upregulates mRNA expression of secreted Ly-6/UPAR-related protein 1 (Slurp1) in cancer cells. The inhibitory effects of lobeline on tumor load and TAM polarization are almost completely eliminated when Slurp1-deficient MC38 cells are subcutaneously injected into mice, suggesting that lobeline exerts an antitumor effect in a Slurp1-dependent manner. Furthermore, using target-responsive accessibility profiling, MAPK14 is identified as the direct target protein of lobeline. Mechanistically, upon binding to MAPK14 in colon cancer cells, lobeline prevents nuclear translocation of MAPK14, resulting in decreased levels of phosphorylated p53. Consequently, negative transcriptional regulation of SLURP1 by p53 is suppressed, leading to enhanced transcription and secretion of SLURP1. Finally, combination therapy using lobeline and anti-PD1 exhibits stronger antitumor effects. Taken together, these findings suggest that remodeling the immunosuppressive microenvironment using small-molecule lobeline may represent a promising therapeutic strategy for CRC.

Ameliorative effect of aqueous leaf extract of Pistacia lentiscus L. against oxaliplatin-induced hepatic injury, oxidative stress, and DNA damage in vitro and in vivo.

The current study aimed to assess the preventive effects of aqueous leaf extract of Pistacia lentiscus (ALEPL) against Oxaliplatin (OXA)-induced DNA damage, hepatic injury, and oxidative stress. The in vitro cytotoxic and genotoxic effects of OXA and ALEPL on HCT116 colon cancer cells were evaluated using the MTT (Tetrazolium salt reduction) assay and comet assay. The in vivo study involved 24 female NMRI (Naval Medical Research Institute) mice that were equally divided into four groups as follows: Control group, ALEPL-treated group (100 mg/kg), OXA-treated group (7 mg/kg), and ALEPL-treated group (100mg/kg) + OXA (7mg/kg). All animals were sacrificed 48 h after OXA treatment. Samples of liver and blood were collected for histopathological, micronucleus, and biochemical analyses. Oxidative stress parameters were also evaluated through non-enzymatic and enzymatic antioxidant activities. Our findings demonstrated that ALEPL contains high phenolic compounds. In the MTT assay, OXA exerted the most potent cytotoxic effect, but ALEPL alone showed no toxic effect in HCT116 cells. Furthermore, OXA administration caused significant DNA fragmentation both in vitro and in vivo, elevated serum biochemical parameters, and confirmed acute liver damage through histopathological observations compared to the control group. OXA exposure also led to a decrease in hepatic glutathione (GSH) and an increase in lipid peroxidation and antioxidant enzyme activities. From the results of our study, ALEPL pretreatment significantly restored the hepatic toxicity and DNA damage as well as the oxidative stress profile induced by OXA.

Canadian Association of Radiologists Cancer Diagnostic Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Cancer Expert Panel is made up of physicians from the disciplines of radiology, medical oncology, surgical oncology, radiation oncology, family medicine/general practitioner oncology, a patient advisor, and an epidemiologist/guideline methodologist. The Expert Panel developed a list of 29 clinical/diagnostic scenarios, of which 16 pointed to other CAR guidelines. A rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of the remaining 13 scenarios. Recommendations from 21 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop the recommendation for these scenarios. During recommendation formulation, one additional scenario was mapped to an existing CAR guideline scenario, leaving 12 scenarios with new recommendations. The guideline focuses on cancer diagnosis and does not cover cancer staging, follow-up, and surveillance. This guideline presents the methods of development and the referral recommendations for suspected pancreatic cancer, suspected liver cancer, incidental liver mass, incidental colon mass or suspected colon cancer, suspected anal cancer, suspected penile cancer, suspected cervical cancer, suspected endometrial/uterine cancer, suspected vulvar cancer, suspected vaginal cancer, suspected haematologic malignancies, and suspected skin cancer. The guideline also points to other CAR guidelines for suspected neck, thyroid, brain, lung, intracardiac/pericardial, esophageal/gastric, renal, adrenal, bladder, testicular, prostate and ovarian cancers, suspected soft tissue mass or tumour, suspected bone tumour, suspected bone tumour --myeloma, suspected spine tumours, and incidental lung cancer.

Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer

BACKGROUND Type II diabetes mellitus (T2DM) has been associated with increased risk of colon cancer (CC) and worse prognosis in patients with metastases. The effects of T2DM on postoperative chemoresistance rate (CRR) and long-term disease-free survival (DFS) and overall survival (OS) in patients with stage III CC who receive curative resection remain controversial. AIM To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III CC. METHODS This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage III CC from 2018 to 2021. Based on preoperative T2DM history, the patients were categorized into non-DM (n = 160) and DM groups (n = 118). The latter was further divided into well-controlled (n = 73) and poorly controlled (n = 45) groups depending on the status of glycemic control. DFS, OS, and CRR were compared between the groups and Cox regression analysis was used to identify risk factors. RESULTS Patients in the DM and non-DM groups demonstrated similar DFS, OS, and CRR (DFS: 72.03% vs 78.75%, P = 0.178; OS: 81.36% vs 83.12%, P = 0.638; CRR: 14.41% vs 7.5%, P = 0.063). Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM (DFS: 62.22% vs 78.07%, P = 0.021; OS: 71.11% vs 87.67%, P = 0.011; CRR: 24.40% vs 8.22%, P = 0.015). High preoperative fasting plasma glucose [DFS: Hazard ratio (HR) = 2.684, P < 0.001; OS: HR = 2.105, P = 0.019; CRR: HR = 2.214, P = 0.005] and glycosylated hemoglobin levels (DFS: HR = 2.344, P = 0.006; OS: HR = 2.119, P = 0.021; CRR: HR = 2.449, P = 0.009) indicated significantly poor prognosis and high CRR, while T2DM history did not (DFS: HR = 1.178, P = 0.327; OS: HR = 0.933, P = 0.739; CRR: HR = 0.997, P = 0.581). CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels, but not T2DM history, were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage III CC.

Rising Burden of Colon and Rectum Cancer in China: An Analysis of Trends, Gender Disparities, and Projections to 2030.

Colon and rectum cancer (CRC) is a major health burden in China, with notable gender disparities. This study was designed to analyze trends in CRC incidence, prevalence, and mortality from 1990 to 2021 and to project future trends. Using data from the Global Burden of Disease (GBD) Study 2021, we examined CRC burden in China, including incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Joinpoint regression, Bayesian age-period-cohort (BAPC) models, and age-period-cohort (APC) analysis identified trends and projected incidence up to 2030. In 2021, CRC incidence was 658,321 cases, disproportionately affecting males, with an age-standardized incidence rate of 42.24 per 100,000 in males and 21.87 per 100,000 in females. The CRC-related deaths reached 275,129, with higher mortality in males (18.95 per 100,000) than females (9.34 per 100,000). The DALYs totaled 6,848,390 and largely impacted males. Joinpoint analysis showed a persistent increase in incidence and prevalence, especially in younger cohorts, whereas mortality declined slightly but began rising again after 2015. The BAPC analysis projected further incidence growth, particularly in males, through 2030. The APC analysis revealed higher CRC risk among younger cohorts, suggesting increasing early-onset CRC linked to lifestyle risk factors, such as smoking, high alcohol consumption, and diets low in fiber and calcium, with a stronger effect on males. The increase of CRC incidence and prevalence in China, particularly among males, underscores the need for targeted prevention and early detection. Future research should address gender disparities and modifiable lifestyle risks through public health interventions.

The impact of apoptosis-inducing MAPK and glycolytic pathways modulated by Aloe vera and royal jelly in lung and colorectal cancer

Lung and colon cancer are among the most commonly diagnosed and fatal cancer types in the world. Due to their metastatic properties, they complicate the treatment process and pose a great threat to human health. These aggressive types of cancer are resistant to chemotherapy drugs. Therefore, it is extremely important to investigate the therapeutic effects of natural compounds. In our previous study, effective doses of Royal Jelly (RJ) (100 mg/mL) and Aloe vera (AVE) (20 µg/mL) were determined and tested separately and in combination on lung and colorectal cancer cells. Glycolytic capacities were determined using the Seahorse XFe24 Analyzer, total transcriptome profiles were sequenced using NovaSeq 6000, and BAX and BCL-2 gene levels were determined using RT-qPCR. It was seen that RJ and RJ + AVE affected glycolytic capacity and more genes in lung cancer cells. In HT29, AVE alone was seen to reduce glycolytic capacity and RJ + AVE combination was seen to reduce the expression level of genes related to cell proliferation and cycle. After RJ + AVE treatments, the apoptotic process which is triggered via MAPK pathway was found in lung cancer. Moreover, BAX levels increased and BCL-2 levels decreased both lung and colorectal cancer cells. It was observed that the combination of RJ and AVE affected the glycolysis process, cell cycle, proliferation and apoptosis on lung and colorectal cancer. In particular, the combination of RJ + AVE was found to be more effective on lung cancer.