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.
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.
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.
Background
Laparoscopic liver resection offers a safe and feasible option primarily for the excision of hepatic neoplasms. Timely recovery of liver volume is a key factor for improving prognosis and ...post-operative mortality of patients undergone liver resection. The aim of the present study was to compare liver regeneration after laparoscopic over open partial hepatectomy.
Methods
Wistar rats were subjected to laparoscopic 70% hepatectomy (group LAP-HEP), open 70% hepatectomy (group HEP), sham operation (group Sham) or no intervention (group Control). At various timepoints following operation (1 h–2 weeks), the liver was excised to assess relative liver weight, thiobarbituric acid reactive substances (TBARS) levels, mitotic activity, tissue expression of Nuclear Factor-κB (NFκB), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) and the histopathologic profile.
Results
No differences were seen in relative liver weight between hepatectomy groups. Mitotic index was increased in all operative study groups, being higher in group LAP-HEP than in group HEP. TBARS levels were higher in group LAP-HEP compared to group HEP. NFκB and VCAM-1 tissue expression scores were increased in all operative study groups with VCAM-1 being higher in group HEP, while ICAM-1 was overexpressed only in hepatectomy groups. Mild histopathologic lesions were noted in hepatectomy groups with the histopathologic score being higher in group HEP (24 h).
Conclusions
Laparoscopic liver resection enhanced hepatocyte mitotic activity which was accompanied by mild oxidative stress and a less pronounced local inflammatory response and tissue injury to that of the open technique.
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 (
= 0.05), deep invasion (
= 0.01), high smooth-muscle actin (SMA) expression (
= 0.01), and high HIF1α and LDH5 expression (
= 0.04). FOXP3
TILs infiltration and FOXP3
/CD8
ratios were higher in inner tumor areas, linked with LDH5 expression, and higher MIB1 proliferation index (
= 0.03) and SMA expression (
= 0.001). Dense CD4
lymphocytic infiltration in the invading front is related to high tumor-budding (TB) (
= 0.04) and angiogenesis (
= 0.04 and
= 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 (
= 0.02, 0.01, 0.02 and 0.006, respectively). High angiogenic activity was linked with high CD4
, FOXP3
, and low CD8
TIL density (
= 0.05, 0.01 and 0.01, respectively), as well as high CD68
macrophage presence (
= 0.003). LDH5 expression was linked with high CD4
and FOXP3
TIL density (
= 0.05 and 0.01, respectively). Further research is needed to explore the prognostic and therapeutic value of TME/TIL interactions.
: 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.
: 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.
: 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.
: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.
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.
IntroductionCataract formation is a prevalent issue worldwide, and understanding the cellular processes involved is crucial to advancing treatment options. The scope of the study was to explore the ...presence of apoptotic cells in the lens epithelium of Greek patients with senile cataracts using transmission electron microscopy (TEM).MethodsTwenty-one patients with senile cataracts were included in this cross-sectional study, and their anterior lens capsules were thoroughly examined. The presence of apoptosis was ultrastructurally investigated, and its association with age, gender, biomicroscopic type of cataract, the coexistence of exfoliation syndrome (XFS), diabetes mellitus, and glaucoma was statistically correlated.ResultsWe detected apoptotic cells in nine of the 21 patients. Morphological features indicative of apoptosis in the nuclei included degradation, nuclear membrane irregularity, reduction of nuclear volume, condensation, and margination of chromatin. The cytoplasm either appeared denser or contained vacuoles. Budding with membrane blebbing and pinopode-like projections were frequently observed. Apoptotic cells appeared smaller, exhibiting loose connections with neighboring cells and the basement membrane (BM). Interestingly, apoptotic bodies were also detected.ConclusionsNone of the examined risk factors showed a connection to apoptosis, whereas neighboring lens epithelial cells (LECs) phagocytose apoptotic bodies, seemingly assumed the role of macrophages. Comparing apoptosis rates between populations with different sun exposure levels could help reveal the relationship between ultraviolet B radiation exposure, apoptosis, and cataract formation.
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.
Aim
: The aim of this study was the correlation of Epstein-Barr virus (EBV) and parvovirus-B19 infections with inflammation levels in placental tissue coming from spontaneous abortions and elective terminations cases. We also investigated whether viral presence could cause spontaneous abortions by associating the expression levels of inflammatory markers with adverse pregnancy outcomes.
Materials and methods
: One hundred ninety-four placental samples were used, 152 included in the study group coming from spontaneous abortions while 42 controls were used from cases of elective terminations. Hematoxylin and eosin (H&E) staining was performed to investigate morphological changes in the tissues, and then indirect immunohistochemistry to evaluate the expression of TNF-α, IL-6, IL-1α, B19, and EBV. Statistical analysis was performed using SPSS v. 19.0 (IBM).
Results
: Higher inflammation levels were observed with statistical significance in the spontaneous abortions group (
p
<0.001) and they were correlated with statistical significance with B19 or EBV presence (
p
<0.001). Viral presence was only found in the spontaneous abortions group. Both simple and multiple logistic regression confirmed that viral presence was an independent prognostic factor for high expression of all inflammatory biomarkers with statistical significance (
p
<0.001).
Conclusions
: Our results clearly indicate a specific pattern. Viral presence can deregulate inflammatory processes in the maternal-fetal environment and thus work as a trigger for spontaneous abortions.
The aim of this study was to assess the antioxidant, photoprotective, and antiaging effects of Greek propolis. Propolis was subjected to n-heptane or methanol extraction. Total phenolic/flavonoid ...content and antioxidant potential were determined in the extracts. Promising extracts were evaluated for their cytoprotective properties using human immortalized keratinocyte (HaCaT) or reconstituted human skin tissue following exposure to UVB. Assessment of cytotoxicity, DNA damage, oxidative status, and gene/protein expression levels of various matrix metalloproteinases (MMPs) were performed. The propolis methanolic fractions exhibited higher total phenolic and flavonoid contents and significant in vitro antioxidant activity. Incubation of HaCaT cells with certain methanolic extracts significantly decreased the formation of DNA strand breaks following exposure to UVB and attenuated UVB-induced decrease in cell viability. The extracts had no remarkable effect on the total antioxidant status, but significantly lowered total protein carbonyl content used as a marker for protein oxidation in HaCaT cells. MMP-1, -3, -7, and -9, monitored as endpoints of antiaging efficacy, were significantly reduced by propolis following UVB exposure in a model of reconstituted skin tissue. In conclusion, propolis protects against the oxidative and photodamaging effects of UVB and could be further explored as a promising agent for developing natural antiaging strategies.
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