Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

The Clinical Significance of Pollen and Fungi Concentrations for Allergic Rhinitis: A Three-Year Study.

INTRODUCTION: The relationship between disease severity and exposure to allergens in allergic rhinitis (AR) patients is not fully clarified presently. We aimed to detect the correlation between airborne pollen and fungi concentrations in a Mediterranean region with symptom scores. METHODS: A total of 98 patients suffering from AR rated their symptoms at the time of exacerbation using the Total 5 Symptoms Score (T5SS) and the Visual Analogue Scale (VAS). Patients' quality of life (QoL) was estimated by using either disease-specific (Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and mini-RQLQ) or generic (Short-Form 36 (SF-36) and Beck Depression Inventory (BDI)) questionnaires. All patients' responses were correlated with aerobiological data. Skin prick tests (SPTs) were used to detect sensitivities to the most common registered pollen and fungi species. RESULTS: A significant positive correlation between total pollen and fungi counts and disease-specific questionnaires was found only for the RQLQ. Accordingly, a significant positive correlation was found between total pollen and fungi counts and T5SS (r = 0.655, p = 0.021), with breathing (r = 0.620, p = 0.032) and sneezing (r = 0.660, p = 0.020) being strongly affected. Moreover, a tendency toward a higher VAS score was found as total pollen and fungi counts increased (r = 0.523, p = 0.081). CONCLUSION: We found a significant correlation between patients' symptoms and pollen and fungal air concentrations. Our results emphasize the clinical significance of pollen and fungi maps in everyday clinical practice.

Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy.

HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome is a life-threatening complication of pregnancy, which is often secondary to preeclampsia. To date, there is no biomarker in clinical use for the early stratification of women with preeclampsia who are under increased risk of HELLP syndrome. Herein, we show that the levels of circulating developmental endothelial locus-1 (DEL-1), which is an extracellular immunomodulatory protein, are decreased in patients with HELLP syndrome compared to preeclampsia. DEL-1 levels are also negatively correlated with the circulating levels of kidney injury molecule-1 (KIM-1), which is a biomarker for disorders associated with kidney damage. Receiver-operating characteristic curve analysis for DEL-1 levels and the DEL-1 to KIM-1 ratio demonstrates that these values could be used as a potential biomarker that distinguishes patients with HELLP syndrome and preeclampsia. Finally, we show that placental endothelial cells are a source for DEL-1, and that the expression of this protein in placenta from patients with HELLP syndrome is minimal. Taken together, this study shows that DEL-1 is downregulated in HELLP syndrome both in the circulation and at the affected placental tissue, suggesting a potential role for this protein as a biomarker, which must be further evaluated.

Development and validation of a prognostic nomogram for overall and disease-specific survival in patients with sarcomatoid urothelial carcinoma.

INTRODUCTION: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data guiding prognosis. In this study, we present the first prognostic nomograms in the literature for 3- and 5-year overall survival (OS) and disease-specific survival (DSS), for patients with SUC derived from the surveillance, epidemiology and end results database (SEER). MATERIALS AND METHODS: Patients with SUC were identified by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8122 (SUC). Patients were randomly divided into a training cohort (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS and DSS were identified with multivariate Cox regression and were used to build the nomograms. Harrel's C-statistic with bootstrap resampling and calibration curves were used for internal (TC) and external (VC) validation. Clinical utility of the nomograms was assessed with the decision curve analysis (DCA). Goodness of fit between the nomograms and the AJCC 8th edition staging system was compared with the likelihood ratio test. RESULTS: A total of 741 patients with SUC were included (507 TC, 234 VC). No statistically significant differences in baseline characteristics were identified between the 2 cohorts. Sex, SEER stage, radical cystectomy and chemotherapy were common variables for the OS and the DSS nomograms with the addition of age in the former. Optimism-corrected C-statistic for the nomograms was 0.68 and 0.67 for OS and DSS respectively. In comparison, C-statistic for AJCC was 0.59 for OS and 0.60 for DSS (P < 0.001). Calibration curves constructed for the nomograms showed appropriate consistency between predicted and actual survival. The nomograms demonstrated optimal clinical utility in the DCA, outperforming the AJCC staging system, by maintaining a higher clinical net benefits than treat all, treat none and AJCC curves, across threshold probabilities. CONCLUSION: We present the first prognostic nomograms developed in patients with SUC. Our models demonstrated superior prognostic performance to the AJCC system, by utilizing a set of variables readily available in daily practice and may serve as useful tools for the individualized risk assessment of these patients.

Tumor Microenvironment and Immune Response in Lip Cancer.

Tumor-infiltrating lymphocytes (TILs) play a significant role in cancer progression and prognosis of patients. The tumor microenvironment (TME) may affect the anti-tumor immune response. We examined the TIL and tertiary lymphoid structure (TLS) density in the invading front and inner tumor stroma, and the lymphocyte subpopulation (CD8, CD4, FOXP3) density in 60 squamous cell carcinomas of the lip. Analysis was performed in parallel with markers of hypoxia (hypoxia-inducible factor (HIF1α), lactate dehydrogenase (LDHA)) and angiogenesis. Low TIL density in the invading tumor front was related with larger tumor size (p = 0.05), deep invasion (p = 0.01), high smooth-muscle actin (SMA) expression (p = 0.01), and high HIF1α and LDH5 expression (p = 0.04). FOXP3+ TILs infiltration and FOXP3+/CD8+ ratios were higher in inner tumor areas, linked with LDH5 expression, and higher MIB1 proliferation index (p = 0.03) and SMA expression (p = 0.001). Dense CD4+ lymphocytic infiltration in the invading front is related to high tumor-budding (TB) (p = 0.04) and angiogenesis (p = 0.04 and p = 0.006, respectively). Low CD8+ TIL density, high CD20+ B-cell density, high FOXP3+/CD8+ ratio and high CD68+ macrophage presence characterized tumors with local invasion (p = 0.02, 0.01, 0.02 and 0.006, respectively). High angiogenic activity was linked with high CD4+, FOXP3+, and low CD8+ TIL density (p = 0.05, 0.01 and 0.01, respectively), as well as high CD68+ macrophage presence (p = 0.003). LDH5 expression was linked with high CD4+ and FOXP3+ TIL density (p = 0.05 and 0.01, respectively). Further research is needed to explore the prognostic and therapeutic value of TME/TIL interactions.

Viral-induced inflammation can lead to adverse pregnancy outcomes.

INTRODUCTION: Parvoviruses are DNA viruses of small size. There have been a number of reports indicating the possible effects of B19 infections during pregnancy. These effects include spontaneous abortions, stillbirth, fetal damage, and quite often, fetal anemia with hydrops fetalis.

Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

Congenital Herpes Simplex Virus: A Histopathological View of the Placenta.

Congenital Herpes simplex virus (HSV) infection is considered a common pregnancy pathology that is not always easy to diagnose. This study aimed to present the spectrum of placental histopathological lesions in pregnancies complicated by HSV infection. MEDLINE and Google Scholar databases were searched using the keywords "HSV" and "placental histopathology" up to June 20, 2022. Study inclusion required presenting placental histopathological anomalies in pregnant women diagnosed with HSV infection antenatally, during labor, or postnatally. Herein, we briefly present placental pathogenesis conditions, which have been correlated with congenital HSV infection, providing clinicians with a short review describing herpetic placental pathology.

CYLD expression in endometrial carcinoma and correlation with clinicohistopathological parameters.

OBJECTIVE: Endometrial cancer is a threat to women health worldwide. Cylindromatosis (CYLD) enzyme is a tumour suppressor, considered an effective prognostic marker in various malignancies, but its role in endometrial carcinoma is not fully elucidated. Here, we sought to estimate the prognostic value of CYLD expression in endometrial carcinoma. MATERIALS AND METHODS: CYLD levels were immunohistochemically evaluated in 65 patients with endometrial carcinoma and inferential statistics were applied. RESULTS: Low or negative CYLD expression significantly correlates with older ages, non-endometrioid and invasive carcinomas, tumours with moderate or poor differentiation and advanced stages. Moreover, non-endometrioid and invasive carcinomas are independent risk factors for weaker CYLD expression. Kaplan-Meier analysis illustrated that negative or low CYLD expression is statistically significantly associated with increased death risk, compared to moderate or high expression. CONCLUSION: This study demonstrates for the first time a clear correlation between CYLD expression and clinicohistopathological parameters of endometrial carcinoma patients, suggesting its use as a potential prognostic/predictive marker for Endometrial Carcinoma.

Gut Barrier Disruption Secondary to Radiofrequency-Assisted Liver Parenchyma Resection in a Porcine Model.

BACKGROUND: Radiofrequency-assisted liver resection (RF-LR) techniques minimize intraoperative blood loss, while avoiding the Pringle maneuver. Both surgical excision and radiofrequency ablation of liver parenchyma compromise gut barrier function with subsequent bacterial translocation. The present study sought to investigate in a porcine model the impact of two RF-LR techniques on the integrity and inflammatory response of the gut barrier. METHODS: Twenty-four pigs were subjected to either (a) partial hepatectomy (PH) employing the "sequential coagulate-cut" technique using a monopolar electrode (SCC group), the one using the bipolar Habib-4X device (group H), or the "crush-clamp" technique (group CC) or (b) sham operation (group Sham). At 48-h post-operation, ileal tissue was excised to be subjected to histopathologic examination, histomorphometric analysis, and immunohistochemical assessment of the mitotic and apoptotic activities and the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and nuclear factor-κB (NFκΒ). RESULTS: Histopathologic score increased in all PH groups, being higher in group SCC, while lower in group H. Villous height decreased in group SCC only. Mitotic index decreased, while apoptotic index increased in all PH groups. An increase in tissue expression score was noted for IL-6 in group CC, for TNFα in all PH groups, being lower in group H compared to group CC, and for NFκB in all PH groups. CONCLUSIONS: The Habib-4X technique for liver resection proved to preserve the integrity of gut barrier, being less injurious in the intestinal mucosa compared to the SCC and CC techniques.

Three-year pollen and fungi calendar in a Mediterranean region of the Northeast Greece.

INTRODUCTION AND OBJECTIVES: Pollen calendars have been proved clinically important in allergic disease management, as differences in airborne allergens exist not only between different countries but also between regions of the same country as well. This study aims to provide new data regarding the atmospheric pollen and fungi content of a Mediterranean region (Western Thrace/North-East Greece) and discuss seasonal trends, differences in pollen grains and fungi spores' circulation over the years, and correlations with climate parameters. MATERIAL AND METHODS: A 7-day continuously running volumetric trap was used to collect circulating pollen grains and fungi spores. Pollen taxa and fungi were characterized by standard protocols and counted as grains /m3 and average total grains and spores. The primary allergenic pollen season was discovered, and their 10-day averages were measured over time. Correlations with temperature, rain, and humidity were assessed by single linear regression analysis. RESULTS: Pollen grains from nine pollen families were identified, including five arboreal, two nonarboreal taxa, and spores from two fungi species. The three most prevalent taxa were Oleaceae, Poaceae, Pinaceae, and Cladosporium in the fungi. Peak pollen concentrations were detected during April and May, with daily averages exceeding 170 grains/m3. Poaceae presented the longest pollen season of 342 days and Oleaceae the shortest, extending to only 110 days, during the 3years. Cladosporium was the fungus with the highest spore concentration (180,129.9 spores) compared with Alternaria (28,026.1 spores). Correlations with meteorological parameters showed variable associations among different taxa, with rainfall and relative humidity being the most significant determinants. CONCLUSION: In this study, the pollenic and fungal spectrum of a Mediterranean region and information that can be proved clinically significant for the appropriate diagnostic and therapeutic approach of allergic patients was presented.

Three-year pollen and fungi calendar in a Mediterranean region of the Northeast Greece

Pollen calendars have been proved clinically important in allergic disease management, as differences in airborne allergens exist not only between different countries but also between regions of the same country as well. This study aims to provide new data regarding the atmospheric pollen and fungi content of a Mediterranean region (Western Thrace/North-East Greece) and discuss seasonal trends, differences in pollen grains and fungi spores’ circulation over the years, and correlations with climate parameters.A 7-day continuously running volumetric trap was used to collect circulating pollen grains and fungi spores. Pollen taxa and fungi were characterized by standard protocols and counted as grains /m3 and average total grains and spores. The primary allergenic pollen season was discovered, and their 10-day averages were measured over time. Correlations with temperature, rain, and humidity were assessed by single linear regression analysis.Results Pollen grains from nine pollen families were identified, including five arboreal, two nonarboreal taxa, and spores from two fungi species. The three most prevalent taxa were Oleaceae, Poaceae, Pinaceae, and Cladosporium in the fungi. Peak pollen concentrations were detected during April and May, with daily averages exceeding 170 grains/m3. Poaceae presented the longest pollen season of 342 days and Oleaceae the shortest, extending to only 110 days, during the 3years. Cladosporium was the fungus with the highest spore concentration (180,129.9 spores) compared with Alternaria (28,026.1 spores). Correlations with meteorological parameters showed variable associations among different taxa, with rainfall and relative humidity being the most significant determinants.Conclusion In this study, the pollenic and fungal spectrum of a Mediterranean region and information that can be proved clinically significant for the appropriate diagnostic and therapeutic approach of allergic patients was presented

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature.

Recurrent implantation failure (RIF) is a multifactorial condition affecting 10-15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients.

Pro-inflammatory cytokines/chemokines, TNF-α, IL-6 and MCP-1, as biomarkers for the nephro- and pneumoprotective effect of silibinin after hepatic ischemia/reperfusion: Confirmation by immunohistochemistry and qRT-PCR.

The present study investigated the potential nephro- and pneumoprotective effect of silibinin (Si) after hepatic ischemia-reperfusion (I/R) injury, by measuring pro-inflammatory factors. Sixty-three rats were randomly assigned into three groups, as follows: (a) the sham group (n = 7 rats), subjected to opening and closing the abdomen; (b) the control group (n = 28 rats), subjected to 45-min hepatic ischemia followed by reperfusion; and (c) the silibinin group (n = 28), subjected to 45-min hepatic ischemia followed by intravenous administration of lyophilised SLB-HP-ß-CD before reperfusion. Control and silibinin groups were further subdivided into time-point groups, according to the duration of reperfusion. TNF-α, IL-6 and MCP-1 expressions were determined immunohistochemically and by qrT-PCR at each time-point. Kidney TNF-α expression was significantly lower at 180 and 240 min, while lung TNF-α expression was significantly lower at 240 min. Comparison between the control and Si group at the same time-points showed very strong evidence of difference at 240 min, with the levels of IL-6 shifting towards lower values in the Si group. Finally, we found a high MCP-1 expression after 120 min. We conclude that hepatic I/R injury remotely increases pro-inflammatory mediators in the kidney and lung, whereas silibinin shows a time-dependent nephro- and pneumoprotective effect.

Differential apoptotic activity in trophoblast of spontaneous abortions and normal pregnancies.

INTRODUCTION: Apoptosis is a key process during normal trophoblastic development and, consequently, the whole gestation. However, in trophoblastic differentiation in spontaneous abortions apoptosis has been hardly investigated. Therefore, the aim of the study was to investigate the correlation between apoptotic frequency in trophoblast and spontaneous abortion incidences. MATERIAL AND METHODS: A total of 72 trophoblastic tissue samples were immunohistochemically examined. 42 of 72 derived from first-trimester spontaneous abortions and the remaining 30 from elective terminations during the same trimester of pregnancy. TUNEL assay and M30 marker were used for apoptosis evaluation by immunohistochemistry. RESULTS: Comparative study of tissues from spontaneous abortions and elective pregnancy terminations demonstrated increased expression of both apoptotic markers in tissues derived from spontaneous abortions compared to normal pregnancies. In addition, statistical analysis correlated maternal age and gravidity with increased spontaneous abortion incidences. Moreover, both M30 and TUNEL staining were significantly correlated with maternal age and primigravidity in spontaneous abortion cases. CONCLUSIONS: Our data proved that elevated apoptotic activity during the first pregnancy trimester is clearly involved in spontaneous abortions. Moreover, two well-established apoptotic markers revealed high statistical significance in the evaluation of post-abortive tissues.

Gut-Barrier Disruption After Laparoscopic Versus Open Major Liver Resection in the Rat.

BACKGROUND: Major liver resection may compromise gut-barrier function, increasing the risk of postoperative infectious complications. The aim of the present experimental study was to compare the effect of the laparoscopic versus the open technique for major liver resection on integrity as well as inflammatory and immune responses of the gut barrier. METHODS: Wistar rats were subjected to open 70% hepatectomy (group H), laparoscopic 70% hepatectomy (group LH), sham operation (group S) or no intervention (group C). At various timepoints (1 hour-1 week) after operation, ileal tissue was excised for oxidative state assessment (TBARS levels), histopathologic examination, histomorphometric analysis, immunohistochemical assessment of the mitotic and apoptotic activity, and tissue expression of inflammatory (interleukin-6, tumor necrosis factor-α, nuclear factor-κB and vascular cell adhesion molecule-1) and immune response biomarkers (CD4+ and CD8+ T-lymphocytes) of the intestinal mucosa. RESULTS: No changes were noted in oxidative state. The histopathologic profile was less deteriorated in group LH compared to group H. Intestinal mucosa atrophy was less intense in group LH compared to group H and was related to an equally compromised crypt cell mitotic activity. Tissue overexpression of interleukin-6, tumor necrosis factor-α, nuclear factor-κΒ, vascular cell adhesion molecule-1, CD4+, and CD8+ T-lymphocytes was less pronounced in group LH compared to group H. CONCLUSION: The employment of the laparoscopic technique for major liver resection in the rat attenuated disruption of the gut barrier compared to the open procedure. This was related to less pronounced inflammatory and immune responses of the intestinal mucosa.

Effect of silibinin on the expression of MMP2, MMP3, MMP9 and TIMP2 in kidney and lung after hepatic ischemia/reperfusion injury in an experimental rat model.

PURPOSE: The protective effect of silibinin on kidney and lung parenchyma during hepatic ischemia/reperfusion injury (IRI) is explored. METHODS: Sixty-three Wistar rats were separated into three groups: sham; control (45 min IRI); and silibinin (200 µL silibinin administration after 45 min of ischemia and before reperfusion). Immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to evaluate the expression levels of MMP2, MMP3, MMP9, and TIMP2 on kidney and lung. RESULTS: Comparing sham vs. control groups, confirmed that hepatic IRI increased both renal and lung MMP2, MMP3, MMP9 and TIMP2 expressions starting at 180 min (p<0.001). Comparison of the control vs. silibinin groups showed a statistically significant decrease in the expression levels of MMP2, MMP3, and MMP9 and increase of TIMP2 in kidney and lung parenchyma. The starting point of this decrease was at 120 min after reperfusion, both for kidney and lung parameters, and it was statistically significant at 240 min (p<0.001) for kidney, while silibinin showed a peak of lung protection at 180 min after hepatic reperfusion (p<0.001). CONCLUSIONS: Hepatic IRI causes distant kidney and lung damage, while a statistically significant protective action, both on kidney and lung parenchyma, is conveyed by the intravenous administration of silibinin.

The positive effect of eugenol on acute pancreatic tissue injury: a rat experimental model.

INTRODUCTION: we present a rat experimental model used to evaluate the possible reduction in the extent of pancreatic tissue injury in acute pancreatitis cases, after administration of eugenol. METHODS: one hundred and twenty Wistar rats were used, which were randomly assigned in 3 groups: sham (n=20), control (n=50) and eugenol (n=50). Acute pancreatitis was induced by biliopancreatic ligation in the control and eugenol groups, but not in the Sham group. In the eugenol group, eugenol was administered per-os. Five histopathological parameters, such as edema, inflammatory infiltration, duct dilatation, hemorrhage and acinar necrosis were evaluated. RESULTS: at 72 h from acute pancreatitis induction, the total histological score was diminished in the eugenol group (p<0.0005) and duct dilatation and inflammatory infiltration were reduced compared to the control group (p<0.05). In addition, at 72 h, eugenol reduced pancreatic myeloperoxidase activity (p<0.0005). CONCLUSION: eugenol, a highly free radical scavenger agent, may have a preventive role in acute pancreatic injury, as it was evident in our rat experimental model.

The hepatoprotective effect of silibinin after hepatic ischemia/reperfusion in a rat model is confirmed by immunohistochemistry and qRT-PCR.

OBJECTIVES: We investigated the positive effect of silibinin after IV administration as silibinin-hydroxypropyl-ß-cyclodextrin lyophilized product, by measuring gene expression and liver tissue protein levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, matrix metalloproteinases matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases-2. METHODS: 63 Wistar rats of age 13.24±4.40 weeks underwent ischemia/reperfusion (I/R) injury of the liver. The animals were randomized into three groups: Sham (S; n = 7); Control (C; n-28); silibinin (Si; n-28). The C and Si groups underwent 45 min ischemia. Si received silibinin-hydroxypropyl-ß-cyclodextrin intravenously immediately before reperfusion at a dose of 5 mg/kg. Both groups were further divided into 4 subgroups, based on euthanasia time (i.e., 60, 120, 180 and 240 min). KEY FINDINGS: qRT-PCR results confirmed the statistically significant reduction of the expression of the pro-inflammatory factors at 240 min after I/R injury (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) and the increase of tissue inhibitor of matrix metalloproteinases-2 in liver tissue in the Si group. Moreover, results of immunohistochemistry levels confirmed that at 240 min pro-inflammatory factors (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases ( matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) had a statistically significantly lower expression in the Si group while tissue inhibitor of matrix metalloproteinases-2 had a higher expression. CONCLUSIONS: Silibinin may have a beneficial effect on the protection of the liver.

A New Controlled Release System for Propolis Polyphenols and Its Biochemical Activity for Skin Applications.

Propolis is a resinous substance produced by bees that exhibits antimicrobial, immunostimulatory and antioxidant activity. Its use is common in functional foods, cosmetics and traditional medicine despite the fact that it demonstrates low extraction yields and inconsistency in non-toxic solvents. In this work, a new encapsulation and delivery system consisting of liposomes and cyclodextrins incorporating propolis polyphenols has been developed and characterized. The antioxidant, antimutagenic and antiaging properties of the system under normal and UVB-induced oxidative stress conditions were investigated in cultured skin cells and/or reconstituted skin model. Furthermore, the transcript accumulation for an array of genes involved in many skin-related processes was studied. The system exhibits significant polyphenol encapsulation efficiency, physicochemical stability as well as controlled release rate in appropriate conditions. The delivery system can retain the anti-mutagenic, anti-oxidative and anti-ageing effects of propolis polyphenols to levels similar and comparable to those of propolis methanolic extracts, making the system ideal for applications where non-toxic solvents are required and controlled release of the polyphenol content is desired.