Diagnostic and prognostic significance of keloid-like collagen remodeling patterns in the extracellular matrix of colorectal cancer.

Background: The desmoplastic reaction is considered a promising prognostic parameter for colorectal cancer. However, intermediate desmoplastic reaction is characterized by sizeable stromal heterogeneity, including both small amounts of keloid-like collagen (KC) in the fibrotic stroma and thick tufts of KC circumferentially surrounding cancer nests and occupying most of the fields of view. The present study aimed to evaluate the diagnostic and prognostic significance of KC histophenotyping with a quantitative visual assessment of its presence in the stroma of the invasive margin of TNM (The "tumor-node-metastasis" classification) stage II/III colorectal cancer (CRC). Methods and results: 175 resected tumors from patients with TNM stage II/III CRC were examined. Keloid-like collagen was assessed according to Ueno H. criteria. KC was assessed at the primary tumor invasive margin using Hematoxylin & Eosin and Masson's trichrome staining. The cut-off point for KC was examined using "the best cutoff approach by log-rank test." Using a cutoff point of 30%, we histologically divided fibrous stroma in the invasive area into two groups: "type A"-KC ≤ 0.3 and "type B"-KC>0.3. Type A stroma was observed in 48% of patients, type B-in 52%. The association between collagen amount and 5-year recurrence-free survival (5-RFS) was assessed using Cox regression analysis. Kaplan-Meier analysis and log-rank tests were used to assess the significance of survival analysis. Analysis of categorical variables showed that increased KC in CRC stroma predicted adverse outcomes for 5-RFS (hazard ratio [HR] = 3.143, 95%, confidence interval [CI] = 1.643-6.012, p = 0.001). Moreover, in Kaplan-Meier analysis, the log-rank test showed that type B exhibited worse 5-RFS than type A (p = 0.000). Conclusion: KC is an independent predictor of 5-year overall and RFS in patients with TNM stage II/III CRC treated with surgery, with worse survival rates when the amount of KC increases by >30%.

Modeling Mediated Crossover Acute and Subacute Damage to the Pulmonary System During Systemic (Subcutaneous) Administration of Bleomycin in Mice to Test the Potential Therapeutic Effect of Polyphenols / Modelado del Daño Agudo y Subagudo Cruzado Mediado al Sistema Pulmonar Durante la Infección Sistémica (Subcutánea) de Administración de Bleomicina a Ratones para Probar el Posible Efecto Terapéutico de los Polifenoles

SUMMARY: The potential anti-inflammatory and antifibrotic activity of polyphenolic extracts of blueberry and grape was evaluated in a mouse model of lung damage induced by subcutaneous administration of bleomycin. The results of testing the polyphenolic extracts on two different systemic administration variants of bleomycin (intraperitoneal and subcutaneous) were compared. It was found that regardless of the method of bleomycin administration, indirect cross-acute and subacute damage to the pulmonary system was observed. Both patterns exhibited the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice resulted in a significant decrease in theseverity of acute and subacute patterns of lung damage, suggesting their protective properties for the microcirculatory bed and a pronounced anti-inflammatory effect.

La potencial actividad antiinflamatoria y antifibrótica de los extractos polifenólicos de arándano y uva se evaluó en un modelo de daño pulmonar en ratón inducido por la administración subcutánea de bleomicina. Se compararon los resultados de las pruebas de los extractos polifenólicos en dos variantes diferentes de administración sistémica de bleomicina (intraperitoneal y subcutánea). Se encontró que, independientemente del método de administración de bleomicina, se observaba daño indirecto cruzado, agudo y subagudo al sistema pulmonar. Ambos patrones exhibieron la misma prevalencia y gravedad. La administración de extractos polifenólicos de arándano y uva a ratones dio como resultado una disminución significativa en la gravedad de los patrones agudos y subagudos de daño pulmonar, lo que sugiere sus propiedades protectoras del lecho micro- circulatorio y un efecto antiinflamatorio pronunciado.

Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft.

This study aimed to compare the new bone formation, the process of remodeling, and the viability of bone grafts, using a combination of platelet-rich plasma (PRP) and Marburg bone graft versus bone grafts without any additional elements. For this study, 48 rabbits (with 24 rabbits in each group) were used. Bone defects were made in the femur, and the bone graft used was the human femoral head prepared according to the Marburg Bone Bank. Rabbits were divided into the following groups: heat-treated bone graft (HTBG group) and HTBG with PRP (HTBG + PRP group). After 14, 30, and 60 days post-surgery, the assessment of the results involved X-ray, histopathological, and histomorphometric analyses. The greater new bone formation was detected in the HTBG + PRP group on the 14 and 30 day (p < 0.001). Furthermore, the group using bone grafts with PRP demonstrated notably enhanced remodeling, characterized by stronger bone integration, more significant graft remineralization, and a circular pattern of newly formed bone. The PRP-bone graft complex improves bone tissue repair in the bone defect in the initial stages of bone regeneration. PRP has been identified to enhance the remodeling process and amplify the osteoconductive and osteoinductive capabilities of HTBGs.

The histological assessment of new bone formation with zolendronic acid loaded bone allograft in rabbit femoral bone defect.

The aim of this experimental study was to evaluate the effect of zolendronic acid (ZOL) combined with bone allograft prepared using the Marburg Bone Bank System on bone formation in the implant remodeling zone. Femoral bone defects with a diameter of 5 mm and a depth of 10 mm were created in 32 rabbits. Animals were divided into 2 similar groups: Group 1 (control), where defects were filled with bone allograft, and Group 2, where allograft was combined with ZOL. Eight animals from each group were sacrificed at 14- and 60-days post-surgery and bone defect healing was assessed using histopathological and histomorphometric analyses after 14 and 60 days. The results showed that new bone formation within the bone allograft was significantly greater in the control group than in the ZOL-treated group after 14 and 60 days (p<0.05). In conclusion, local co-administration of ZOL on heat-treated allograft inhibits allograft resorption and new bone formation in the bone defect.

Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress.

The current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-α and IFN-γ levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4-induced hepatotoxicity in rats.