Search Results (1,540)

Background and Objectives: Mucinous adenocarcinoma (MAC) and mucinous components (MCP) in colorectal cancers (CRC) have shown conflicting results regarding their prognostic impact. This study aims to evaluate survival differences between MAC, MCP, and non-mucinous adenocarcinoma (nMAC) in stage II and III CRC patients. Materials and Methods: 224 CRC patients who underwent surgery between 2013 and 2021 were analyzed retrospectively. Patients were classified as nMAC, MCP, or MAC based on the percentage of extracellular mucin. Those who received neoadjuvant therapy, had stage I or IV TNM disease, and emergency cases were excluded. Survival analysis was performed using Kaplan–Meier curves and Cox regression models. Results: MAC patients showed worse survival outcomes compared to nMAC (p = 0.025). No difference in survival was found between MCP and nMAC (p = 0.055). Multivariate analysis identified MAC (OR: 2.814; p = 0.014) and perineural invasion (PNI) (OR: 2.283; p = 0.008) as independent factors associated with worse survival. Kaplan–Meier analysis revealed MAC’s worse prognosis than nMAC (p = 0.027). Conclusions: MAC was shown to have a worse prognosis than nMAC in stage II and III CRC patients, while MCP survival rates were similar with nMAC. These findings suggest that MAC requires more careful treatment approaches, while MCP and nMAC have better survival rates. Further studies focusing on molecular and genetic profiles are needed to better understand these outcomes. Full article

With advances in the treatment of Crohn’s disease (CD), the number of long-term cases is increasing, along with the incidence of CD-related cancers. Here, we discuss the clinical features, diagnosis, treatment, prognosis, and surveillance of CD-related cancers. There are regional differences in the common sites and histological types of CD-related cancers, with right-sided colon cancer accounting for 40% of cases in Europe and the US, and squamous cell carcinoma being common. In Japan, rectal and anal cancers account for 80% of cases, and mucinous carcinoma is common. The prognosis of CD-associated colon cancer and sporadic colon cancer is the same; however, the prognosis of CD-associated rectal cancer is clearly worse than that of sporadic rectal cancer. Early diagnosis is important to improve the prognosis of CD-associated rectal cancer, and it is necessary to establish a surveillance method for CD-associated cancer that combines colonoscopy, anesthetic proctoscopy, and imaging, as appropriate. The basic treatment for CD-related cancer is surgical resection; however, the criteria for selecting the surgical procedure are unclear, and there is no clear evidence for multidisciplinary perioperative treatment including chemotherapy and radiotherapy. Additionally, CD-related rectal and anal cancers have a higher local recurrence rate than that of sporadic rectal cancers; therefore, thorough local control is important. Furthermore, CD-related cancers have different epidemiologies in different regions; therefore, unique diagnostic and treatment strategies must be established for each region. Full article

Background/Objectives: The number of older adults requiring a kidney transplant (KT) is increasing; hence, postoperative sarcopenia prevention is necessary. KT recipients require permanent oral immunosuppressants (ISs), and the gut microbiota (GM) plays a role in various systemic diseases. However, few studies have evaluated post-kidney transplantation frailty and the associations among ISs, GM, and muscle mass alterations. Therefore, we investigated the effects of ISs on GM and skeletal muscle mass in mice and human KT recipients. Methods: Mice were treated with six different ISs, and their skeletal muscle mass, GM diversity, and colonic mucosal function were assessed. Human KT recipients and donors were monitored before and after surgery for 1 year, and GM diversity was evaluated before and 1 month after surgery. Results: The abundance of Akkermansia, crypt depth, and mucin 2 expression were lower in tacrolimus- and prednisolone-treated mice. The psoas muscle volume changes at 1 month and 1 year after surgery were lower in KT recipients than in donors. Furthermore, the beta diversity was significantly different between the operative groups (p = 0.001), and the KT group showed the lowest Shannon index. Conclusions: The findings of this study indicate potential links among ISs, GM, and muscle mass decline. Further investigation is required to improve therapeutic strategies and patient outcomes. Full article

Several immunoregulatory or immune checkpoint receptors including T cell immunoglobulin and mucin domain 3 (TIM-3) have been implicated in glioblastoma progression. Rigorous investigation over the last decade has elucidated TIM-3 as a key player in inhibiting immune cell activation and several key associated molecules have been identified both upstream and downstream that mediate immune cell dysfunction mechanistically. However, despite several reviews being published on other immune checkpoint molecules such as PD-1 and CTLA-4 in the glioblastoma setting, no such extensive review exists that specifically focuses on the role of TIM-3 in glioblastoma progression and immunosuppression. Here, we critically summarize the current literature regarding TIM-3 expression as a prognostic marker for glioblastoma, its expression profile on immune cells in glioblastoma patients and the exploration of anti-TIM-3 agents in glioblastoma pre-clinical models for potential clinical application. Full article

Background: As the population ages, enhancing immune function is crucial to mitigating age-related physiological decline. Since immunostimulant drugs are known to have potential side effects, medicinal plants emerge as promising candidates offering a safer alternative. To leverage the advantages of medicinal plants with fewer side effects and develop a potent immune-enhancing agent, we investigated the efficacy of a novel immunomodulatory candidate derived from the combination of Angelica gigas and Pueraria lobata (CHL). Methods: In vitro, CHL was treated in RAW 264.7 macrophages at various time points, and the experiments conducted in the study were performed using ELISA, Western blot, and RT-qPCR analysis. In vivo, C57BL/6 mice were administrated CHL for 16 days (p.o.) and CTX on the three days (i.p.), and experiments were conducted with ELISA, western blot, RT-qPCR analysis, H&E staining, flow cytometry, gut microbiome, and correlation analysis. Results: In vitro, CHL has upregulated NO and cytokines expression, substantially enhancing the NF-κB and MAPK activation. Furthermore, CHL promoted the TAK1, TRAF6, and MyD88 via TLR2/6 signaling. In vivo, the CHL improved the reduced body weight and immune organs’ indices and recovered various cytokines expression, NK cell cytotoxicity activity, and immune cell population. CHL also improved the histological structure and tight junction markers, mucin-2, and TLR2/6 in the intestines of CTX-induced mice. Conclusions: Overall, CHL demonstrated immunostimulatory potential by enhancing immune responses and restoring immune function, suggesting its promise as a safe and effective immune-enhancing agent. Full article

Background and Objectives: Early-onset colorectal cancer (EO-CRC) has become a significant public health concern due to its alarming rise in incidence and the poor prognosis associated with this disease. The aim of our study was to identify epidemiological, clinical, and paraclinical characteristics that could explain the more aggressive evolution of EO-CRC compared to late-onset colorectal cancer (LO-CRC). Materials and Methods: We conducted a retrospective study over a two-year period, including 204 patients diagnosed with colorectal cancer (CRC). The patients were divided into two subgroups: those with EO-CRC and those with LO-CRC. Statistical analysis was performed using IBM SPSS Statistics, Version 29.0. Results: EO-CRC was identified in 11.3% of the patients included in the study. Compared to LO-CRC patients, EO-CRC patients exhibited a tendency for more distal tumor localization and a stenotic endoscopic appearance (43.5% vs. 29.3%). Regarding histopathological diagnosis, EO-CRC patients demonstrated a higher proportion of the mucinous histologic subtype (34.8% vs. 14.4%) and a significantly greater percentage of poorly differentiated tumors (39.1% vs. 14.5%; p = 0.010). Immunohistochemical results, available for a limited number of patients, revealed higher CDX2 positivity in LO-CRC patients (p = 0.012) and higher HER2 positivity in EO-CRC patients (p = 0.002). Smoking (p = 0.006) and hypertension (p = 0.002) were more prevalent in EO-CRC patients than in LO-CRC patients. Conclusions: Patients with EO-CRC exhibit distinct histopathological and molecular characteristics compared to those with LO-CRC, which may contribute to their poorer prognoses. The higher prevalence of the mucinous histological subtype, poor tumor differentiation, increased HER2 expression, and reduced CDX2 expression suggest potential molecular pathways driving the aggressive nature of EO-CRC. These findings highlight the need for tailored screening strategies and personalized therapeutic approaches in younger CRC patients. Future studies should further investigate the underlying mechanisms and potential biomarkers that could guide early diagnoses and targeted treatments. Full article

Mucinous cystic neoplasm of the liver (MCN-L) is a rare benign tumor accounting for less than 5% of all liver cysts, with MCN-L in the hilar region being exceptionally uncommon and often misdiagnosed due to its complex presentation. A 48-year-old woman presented with obstructive jaundice following initial laparoscopic drainage of hepatic cysts, where pathology initially indicated benign cystic lesions. Months later, imaging revealed an enlarged cystic lesion in the left liver lobe with intrahepatic bile duct dilation. Further evaluations, including ultrasound, enhanced CT, and MRI, confirmed a large cystic lesion compressing the intrahepatic bile ducts. After a multidisciplinary discussion, hepatic cyst puncture and drainage were performed, temporarily alleviating jaundice. However, she returned with yellowish-brown drainage fluid and worsening jaundice, prompting cyst wall resection. Postoperative pathology confirmed MCN-L. Three months later, jaundice subsided, and a hepatic resection of segment 4 was performed, with pathology confirming low-grade MCN-L. At a 12-month follow-up, the patient showed no abnormalities. This case highlights the diagnostic and therapeutic challenges of MCN-L in the hilar region, as it can easily be mistaken for other liver cystic lesions on imaging. Pathologic examination is essential for definitive diagnosis, and early radical surgical resection is critical to improve prognosis and reduce the risk of malignancy and recurrence. Full article

The increasing use of high-resolution cross-sectional imaging has significantly enhanced the detection of pancreatic cystic lesions (PCLs), including pseudocysts and neoplastic entities such as IPMN, MCN, and SCN. However, accurate categorization of PCLs remains a challenge. This study aims to improve PCL evaluation by developing and validating a radiomics-based software tool leveraging machine learning (ML) for lesion classification. The model categorizes PCLs into mucinous and non-mucinous types using a custom dataset of 261 CT examinations, with 156 images for training and 105 for external validation. Three experienced radiologists manually delineated the images, extracting 38 radiological and 214 radiomic features using the Pyradiomics module in Python 3.13.2. Feature selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by classification with an Adaptive Boosting (AdaBoost) model trained on the optimized feature set. The proposed model achieved an accuracy of 89.3% in the internal validation cohort and demonstrated robust performance in the external validation cohort, with 90.2% sensitivity, 80% specificity, and 88.2% overall accuracy. Comparative analysis with existing radiomics-based studies showed that the proposed model either outperforms or performs on par with the current state-of-the-art methods, particularly in external validation scenarios. These findings highlight the potential of radiomics-driven machine learning approaches in enhancing PCL diagnosis across diverse patient populations. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic databases were used for mutational correlation analysis. p-value ≤ 0.05 was considered as significant. Results: A total of thirty-nine patients with resected IPMN with complete clinical and sequencing data were identified and included in the final cohort. The male-to-female distribution was 21:18, and the mean age was 70.1 ± 9.1 years. GNAS mutations occurred in 23.1% of patients, and 89.7% of patients had iIPMN. In iIPMN patients, GNAS mutation was strongly associated with improved disease-free survival: all GNAS-mutant patients survived to follow-up with significantly fewer recurrences than in GNAS wild-type (WT) patients (p = 0.013). Mutated GNAS closely co-occurred with wild-type KRAS (p < 0.001), and further analysis of large genomic PDAC datasets validated this finding (OR 3.47, p < 0.0001). Conclusions: Our study suggests prognostic value of mutational status in malignant resected IPMNs. WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations. Full article

In this article, we introduce nano-differential fluorimetry (nano-DSF) as an analytical technique that is suitable for investigating polyphenol–protein interactions in solution. Nano-DSF monitors conformational changes in proteins induced by external agents upon interaction at the molecular level. We demonstrate the suitability of this technique to qualitatively monitor an interaction between selected dietary polyphenols and selected proteins including BSA, ovalbumin, amylase, pepsin, trypsin, mucin and ACE-1. Protein conformational changes induced by dietary polyphenols can be investigated. As a major advantage, measurements are carried out at a high dilution, avoiding the precipitation of polyphenol–protein complexes, allowing the rapid and efficient acquisition of quantitative and qualitative binding data. From this concentration, quantitative binding data could be obtained from the fluorescence response curve in line with published values for the association constants. We demonstrate that qualitative interactions can also be established for real food extracts such as cocoa, tea or coffee containing mixtures of dietary polyphenols. Most importantly, we demonstrate that polyphenols of very different structural classes interact with the same protein target. Conversely, multiple protein targets show an affinity to a series of structurally diverse polyphenols, therefore suggesting a dual level of promiscuity with respect to the protein target and polyphenol structure. Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article

T cell phenotypes and kinetics are emerging as crucial factors associated with immunotherapeutic responses in a wide range of solid cancer types. However, challenges remain in understanding the spatial and temporal profiles of T cells with differential phenotypes due to difficulties in single-cell analysis with preserved tissue structures. Here, we provide an optimized 12-marker multiplex immunohistochemical (IHC) panel and single-cell-based quantitative assessment to identify the spatial distributions of T cell phenotypes in formalin-fixed paraffin-embedded sections. This panel revealed differential T cell populations with spatial localizations in human tonsil tissue, where the percentages of CD8⁺ T cell-expressing programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin domain 3 (TIM3), and other T cell phenotypic markers vary by tonsillar tissue components such as follicles, parenchyma, and epithelium. A specimen from salivary gland adenocarcinoma during hyper-progression, followed by anti-PD-1 treatment, exhibited the exclusion of CD8⁺ T cells from the intratumoral regions. Although the vast majority of peritumoral CD8⁺ T cells exhibited proliferative effector T cell phenotypes with PD-1⁻TIM3⁻Ki67⁺CD45RA⁺, intratumoral CD8⁺ T cells showed exhausted phenotypes with PD-1⁺TIM3⁻ and increased Eomes expression, which might be related to poor therapeutic response in this case. To verify these findings in the context of temporal changes, we analyzed six longitudinal samples from a single patient with maxillary sinus cancer, observing increased T cell exhaustion along with metastasis and progression. Together, highly multiplexed IHC can be applied to analyze the spatiotemporal phenotypes of T cells, potentially contributing to the understanding of the mechanisms of resistance to immunotherapy. Full article

Objectives: Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. Materials and Methods: A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. Results: A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol (p = 0.005 and p = 0.031), with a marked reduction in CF lymphocytes (p = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). Conclusions: CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration. Full article

Carrageenan (CGN) has side effects on the intestinal barrier. Damage to the intestinal barrier is associated with exposure to sulfate groups. Food matrix has significant influence on the exposure quantity of sulfate groups and conformation in κ-CGN, but the corresponding side effects are not reported specifically. This study aimed to explore the regulatory effect of κ-CGN dissolved in aqueous (κ-CGN) and in 3% casein (κ-carrageenan-casein, κ-CC) on the intestinal barrier and microbiota homeostasis. Research has shown that both κ-CGN and κ-CC can induce different extents of intestinal barrier damage through disrupting microbiota homeostasis. Importantly, κ-CGN in casein with lower sulfate groups content was found to repair the intestinal barrier injury induced by an equivalent dose of κ-CGN aqueous through increasing the abundance of Oscillibacter and decreasing Weissella. These alleviating effects were reflected in lower levels of tumor necrosis factor (TNF)-α and C-reaction protein (CRP), higher levels of interleukin (IL)-10, raised secretion of mucus and goblet cells, and improved expression of epithelial cell compact proteins zonula occluden (ZO)-1 and mucin protein 2 (MUC2). This study states that κ-CGN in casein has a positive regulatory effect on the intestinal barrier damage compared to in aqueous solution, which can provide guidance for processing and utilization of CGN. Full article