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Background Mesenchymal stem cells (MSCs) therapy is a novel treatment strategy for cancer and a wide range of diseases with an excessive immune response such as ulcerative colitis (UC), due to its powerful immunomodulatory properties and its capacity for tissue regeneration and repair. One of the promising therapeutic options can focus on MSC-secreted exosomes (MSC-Exo), which have been identified as a type of paracrine interaction. In light of a wide variety of recent experimental studies, the present review aims to seek the recent research advances of therapies based on the MSC-Exo for treating UC and colorectal cancer (CRC). Methods A systematic literature search in MEDLINE, Scopus, and Google Scholar was performed from inception to December 2021 using the terms [(“colorectal cancer” OR “bowel cancer” OR “colon cancer” OR “rectal cancer”) AND (exosome) AND (stem cell) AND (“inflammatory bowel disease” OR “Crohn's disease” OR “colitis”)] in titles and abstracts. Findings Exosomes derived from various sources of MSCs, including human umbilical cord-derived MSCs (hUC-MSCs), human adipose-derived MSCs (hAD-MSCs), human bone marrow-derived MSCs (hBM-MSCs), and olfactory ecto-MSCs (OE-MSCs), have shown the protective role against UC and CRC. Exosomes from hUC-MSCs, hBM-MSCs, AD-MSCs, and OE-MSCs have been found to ameliorate the experimental UC through suppressing inflammatory cells including macrophages, Th1/Th17 cells, reducing the expression of proinflammatory cytokines, as well as inducing the anti-inflammatory function of Treg and Th2 cells and enhancing the expression of anti-inflammatory cytokines. In addition, hBM-MSC-Exo and hUC-MSC-Exo containing tumor-suppressive miRs (miR-3940-5p/miR-22-3p/miR‐16‐5p) have been shown to suppress proliferation, migration, and invasion of CRC cells via regulation of RAP2B/PI3K/AKT signaling pathway and ITGA2/ITGA6. Key messages The MSC-Exo can exert beneficial effects on UC and CRC through two different mechanisms including modulating immune responses and inducing anti-tumor responses, respectively.

Frailty is a significant factor contributing to an increased risk of adverse clinical outcomes in older cancer patients. This study aims to investigate the impact of the 5-item modified frailty index (mFI) on both short-term and long-term prognosis in elderly rectal cancer patients who underwent radical resection. And, by integrating the 5-item mFI with clinicopathological characteristics, a postoperative severe complications nomogram and a cancer-specific survival (CSS) prediction nomogram were further constructed. Demographic, clinical, and therapeutic data were collected from 1,034 patients aged ≥ 70 years with rectal cancer who underwent proctectomy between 2017 and 2022. Patients were categorized into three groups based on their mFI scores: 318 patients with mFI = 0, 404 patients with mFI = 1, and 312 patients with mFI ≥ 2. Comparisons among these groups revealed that higher 5-item mFI scores were associated with an increased incidence of both overall and severe postoperative morbidity, prolonged recovery times, and elevated total medical costs. Multivariate logistic regression analysis indicated that an mFI score of ≥ 2 [odds ratio = 2.856, 95% confidence interval (CI): 1.542–5.290, P  < 0.001] was an independent risk factor for severe postoperative complications. Similarly, in competing risk analysis, the 5-item mFI was identified as an independent prognostic factor for CSS (subdistribution hazard ratio = 2.00, 95% CI: 1.47–2.72, P  < 0.001). The postoperative severe complications nomogram and CSS prediction nomogram AUC values were 0.726 and 0.844, respectively, both demonstrating promising predictive capabilities. In conclusion, the 5-item mFI serves as a concise and effective tool for preoperative frailty stratification and for predicting clinical outcomes in elderly rectal cancer patients.

Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70–74; 75–79; 80–84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.

Appendectomy impacts the homeostasis of gut microbiome in patients. We aimed to study the role of appendectomy in colorectal cancer (CRC) risk through causing gut microbial dysbiosis. Population-based longitudinal study (cohort 1, n  = 129,155) showed a 73.0% increase in CRC risk among appendectomy cases throughout 20 years follow-up (Adjusted sub-distribution hazard ratio (SHR) 1.73, 95% CI 1.49–2.01, P  < 0.001). Shotgun metagenomic sequencing was performed on fecal samples from cohort 2 ( n  = 314). Gut microbial dysbiosis in appendectomy subjects was observed with significant enrichment of 7 CRC-promoting bacteria ( Bacteroides vulgatus, Bacteroides fragilis, Veillonella dispar, Prevotella ruminicola, Prevotella fucsa, Prevotella dentalis, Prevotella denticola ) and depletion of 5 beneficial commensals ( Blautia sp YL58, Enterococcus hirae, Lachnospiraceae bacterium Choco86, Collinsella aerofaciens, Blautia sp SC05B48 ). Microbial network analysis showed increased correlation strengths among enriched bacteria and their enriched oncogenic pathways in appendectomy subjects compared to controls. Of which, B. fragilis was the centrality in the network of the enriched bacteria. We further confirmed that appendectomy promoted colorectal tumorigenesis in mice by causing gut microbial dysbiosis and impaired intestinal barrier function. Collectively, this study revealed appendectomy-induced microbial dysbiosis characterized by enriched CRC-promoting bacteria and depleted beneficial commensals, signifying that the gut microbiome may play a crucial role in CRC development induced by appendectomy.

Increasing antibiotic resistance to bacterial infections causes a serious threat to human health. Efficient detection and treatment strategies are the keys to preventing and reducing bacterial infections. Due to the high affinity and antigen specificity, antibodies have become an important tool for diagnosis and treatment of various human diseases. In addition to conventional antibodies, a unique class of “heavy-chain-only” antibodies (HCAbs) were found in the serum of camelids and sharks. HCAbs binds to the antigen through only one variable domain Referred to as VHH (variable domain of the heavy chain of HCAbs). The recombinant format of the VHH is also called single domain antibody (sdAb) or nanobody (Nb). Sharks might also have an ancestor HCAb from where SdAbs or V-NAR might be engineered. Compared with traditional Abs, Nbs have several outstanding properties such as small size, high stability, strong antigen-binding affinity, high solubility and low immunogenicity. Furthermore, they are expressed at low cost in microorganisms and amenable to engineering. These superior properties make Nbs a highly desired alternative to conventional antibodies, which are extensively employed in structural biology, unravelling biochemical mechanisms, molecular imaging, diagnosis and treatment of diseases. In this review, we summarized recent progress of nanobody-based approaches in diagnosis and neutralization of bacterial infection and further discussed the challenges of Nbs in these fields.

Background Extrachromosomal circular DNA (eccDNA) has potential in tumor diagnosis, particularly for improving diagnostic accuracy and early cancer detection; however, many challenges remain in its application to clinical practice. Methods We conducted a Circle‐Seq analysis on clinical samples at different stages of colorectal cancer progression to examine the dynamic changes of eccDNA during the progression of colorectal cancer. We used breakpoint-specific PCR to verify candidate eccDNAs identified by Circle‐Seq. The results were further validated using the AOM/DSS-induced colorectal cancer model. Results There was an increase in the abundance of eccDNA with the progression of colorectal cancer. The genes associated with these eccDNA molecules were primarily related to signaling pathways involved in tumor development and metastasis. Our analysis also revealed that eccDNA abundance positively correlates with gene expression, and eccDNA derived from specific genes has potential value for the early diagnosis of tumors. Conclusions This study revealed a connection between eccDNA and colorectal cancer progression and highlights the clinical potential of eccDNA for the early diagnosis of colorectal cancer.

Tumor tissues contain both tumor and non-tumor cells, which include infiltrated immune cells and stromal cells, collectively called the tumor microenvironment (TME). Single-cell RNA sequencing (scRNAseq) enables the examination of heterogeneity of tumor cells and TME. In this review, we examined scRNAseq datasets for multiple cancer types and evaluated the heterogeneity of major cell type composition in different cancer types. We further showed that endothelial cells and fibroblasts/myofibroblasts in different cancer types can be classified into common subtypes, and the subtype composition is clearly associated with cancer characteristic and therapy response.

Tumor budding is a long-established independent adverse prognostic marker for colorectal cancer (CRC), yet assessment of tumor budding was not reproducible. Therefore, development of precise diagnostic approaches to tumor budding is in demand. In this study, we first performed bioinformatic analysis in our single-center CRC patients’ cohort (n = 84) and identified tumor budding-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify hub genes and construct a prognostic signature. Nomogram model was used to identified hub genes score for tumor budding, and the receiver operating characteristic (ROC) curve and calibration plot indicated high accuracy and stability of hub gene score for predicted the prognosis of CRC. The association between budding-associated hub genes and score and prognosis of CRC were further verified in TCGA CRC cohort (n = 342). Then gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to explore the signaling pathways related to the tumor budding and validated by immunohistochemistry (IHC) of our clinical samples. Subsequently, immune infiltration analysis demonstrated that there was a high correlation between hub genes score and M2-like macrophages infiltrated in tumor tissue. In addition, somatic mutation and chemotherapeutic response prediction were analyzed based on the risk signature. In summary, we established a tumor budding diagnostic molecular model, which can improve tumor budding assessment and provides a promising novel molecular marker for immunotherapy and prognosis of CRC.

PD-1/PD-L1 immune checkpoint inhibitors are currently the most commonly utilized agents in clinical practice, which elicit an immunostimulatory response to combat malignancies. However, all these inhibitors are currently administered injection using antibody-based therapies, while there is a growing need for oral alternatives. This study has developed and synthesized exosome-wrapped gold-peptide nanocomplexes with low immunogenicity, which can target PD-L1 and activate antitumor immunity through oral absorption. The PDL1 was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and gel silver staining. The transmembrane ability of PDL1 was evaluated by flow cytometry and immunofluorescence. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) assay. ELISA experiments were conducted to detect serum and tissue inflammatory factors, as well as serum biochemical indicators. Tissue sections were stained with H&E for the evaluation of the safety of PDL1 . An MC38 colon cancer model was established in immunocompetent C56BL/6 mice to evaluate the effects of PDL1 on tumor growth . Immunohistochemistry (IHC) staining was performed to detect cytotoxicity factors such as perforin and granzymes. First, PDL1 was successfully synthesized, and milk exosome membranes were encapsulated through ultrasound, repeated freeze-thaw cycles, and extrusion, resulting in the synthesis of PDL1 . Multiple characterization results confirmed the successful synthesis of PDL1 nanoparticles. Furthermore, our data demonstrated that PDL1 exhibited excellent colloidal stability and superior cell transmembrane ability. and experiments revealed that PDL1 did not cause damage to multiple systemic organs, demonstrating its good biocompatibility. Finally, in the MC38 colon cancer mouse model, it was discovered that PDL1 could inhibit the progression of colon cancer, and this tumor-suppressive effect was mediated through the activation of tumor-specific cytotoxic T lymphocyte (CTL)-related immune responses. This study has successfully designed and synthesized an oral nanotherapeutic, PDL1 , which demonstrates small particle size, excellent colloidal stability, transmembrane ability in tumor cells, and biocompatibility. experiments have shown that it effectively activates T-cell immunity and exerts antitumor effects.

Purpose Robotic lateral lymph node dissection (LLND) has been described as a safe and feasible procedure for local advanced rectal cancer. The aim of this study was to evaluate the learning curve for robotic-assisted LLND. Methods We collected data on 78 consecutive patients who underwent robotic-LLND at our hospital. The learning curve was analyzed using the cumulative sum (CUSUM) method to assess changes in the unilateral LLND operative times across the case sequence. Results Among the 78 patients, 52 underwent bilateral LLND and 26 underwent unilateral LLND. A total of 130 consecutive data were recorded. We arranged unilateral robotic-LLND operative times and calculated cumulative sum values, allowing the differentiation of three phases: phase I (learning period, cases 1–51); phase II (proficiency period, cases 52–83); and phase III (mastery period, cases 84–130). As the learning curve accumulated, the operation time and estimated blood loss of unilateral robotic-LLND decreased significantly with each phase ( P  < 0.05). By 12 months after surgery, the International Prostatic Symptom Score of patients at phase III was significantly lower than at phase I ( P  < 0.05). Conclusion The CUSUM curve shows three phases in the learning of robotic-LLND. The estimated learning curve for robotic-assisted rectal-LLND is achieved after 51 cases.