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Due to the development of obstetric and neonatal care, the perinatal mortality rate is gradually decreasing both in the Russian Federation and worldwide. This trend is due to a decline in early neonatal mortality, while the stillbirth rate is becoming a priority by gradually increasing its contribution to perinatal mortality. Despite of development of modern methods of prenatal diagnosis, assessment of biochemical markers of complications of pregnancy, routing of high-risk patients to an expert ultrasonography the problem of antenatal fetal death is not yet conclusive. In developed countries, the rate of stillbirths due to unknown causes is as high as 60% and in the Russian Federation 4.7%. The most common problem in determining thanatogenesis of the case of antenatal fetal death during pregnancy. The aim of the research – compare the pathological features of the placenta at antenatal fetal death and live birth in the outcome of a timely birth using histological and immunohistochemical examination. Materials and methods. The study includes 60 women whose pregnancy was completed in full term of pregnancy (37 weeks 0 days – 41 weeks 6 days). 1 group – patients with antenatal fetal death (n = 30), 2 group – women having a live birth in the outcome of pregnancy (n = 30). A comparative histological and immunohistochemical study of the placenta with determination of the level of expression of GLUT1, HIF-1α and CASP-3 markers was conducted. Results. Mostly antenatal death of the full-term fetus was accompanied by signs of chronic placental insufficiency and hypoxic damage to the stromal-vascular placental part. There has been a statistically significant decrease in GLUT-1 expression and an increase in HIF-1α and CASP-3 expression in placenta of patients with antenatal fetal death in full-term pregnancy. Conclusion. Therefore, the disruption of placenta’s energy function, more pronounced processes of apoptosis and hypoxic tissue damage in patients with antenatal death of full-term fetus correlate with histological signs of chronic placental insufficiency and changes in stromal-vascular tract in patients with antenatal full-term fetal death. Further research into placental abnormalities is needed to prevent adverse outcomes of pregnancy.

20α-hydroxysteroid dehydrogenase (20α-HSD) is a member of the aldo-keto reductase family. These enzymes play a pivotal role in regulating steroid hormones, such as androgens, oestrogen, and progesterone, and are, therefore, considered vital targets for determining whether a pregnancy is maintained. In this study, we investigated the association between 20α-HSD and apoptosis-related genes in luteal tissues (at 30, 60, and 90 days of gestation) and cells from early gestation in cattle. The corpus luteum altered the number of large lutein cells from 30-90 days. The change in the junction of the connective tissue appeared to affect the density of the corpus luteum. In addition, 20α-HSD was detected in the corpus luteum and cultured cells during early pregnancy, in contrast to the results of previous studies. The overall expression pattern of the 20α-HSD and Casp-3 proteins was lower on day 50 of gestation than on days 30 and 90. However, the 20α-HSD expression gradually increased from 30 to 90 days of gestation. When the 20α-HSD protein was increased to 0.5 μg/ml, 1 μg/ml, and 1.5 μg/ml in the luteal cells collected on day 30 of pregnancy, apoptosis was analysed after 48 hours. 20α-HSD generated in the cells was confirmed, and the concentration gradually decreased as the concentration increased. However, the expression of Casp-3 showed an overall similar expression pattern. Notably, the 20α-HSD and Casp-3 proteins were lowest at 1.5 μg/ml supplemented with 20α-HSD, with higher levels in the cytosol than in the cytoplasm. These results suggest that 20α-HSD plays a role in maintaining normal pregnancy, particularly by regulating the progesterone concentrations during luteal cell development.

20α-hydroxysteroid dehydrogenase (20α-HSD) is a member of the aldo-keto reductase family. These enzymes play a pivotal role in regulating steroid hormones, such as androgens, oestrogen, and progesterone, and are, therefore, considered vital targets for determining whether a pregnancy is maintained. In this study, we investigated the association between 20α-HSD and apoptosis-related genes in luteal tissues (at 30, 60, and 90 days of gestation) and cells from early gestation in cattle. The corpus luteum altered the number of large lutein cells from 30–90 days. The change in the junction of the connective tissue appeared to affect the density of the corpus luteum. In addition, 20α-HSD was detected in the corpus luteum and cultured cells during early pregnancy, in contrast to the results of previous studies. The overall expression pattern of the 20α-HSD and Casp-3 proteins was lower on day 50 of gestation than on days 30 and 90. However, the 20α-HSD expression gradually increased from 30 to 90 days of gestation. When the 20α-HSD protein was increased to 0.5 μg/ml, 1 μg/ml, and 1.5 μg/ml in the luteal cells collected on day 30 of pregnancy, apoptosis was analysed after 48 hours. 20α-HSD generated in the cells was confirmed, and the concentration gradually decreased as the concentration increased. However, the expression of Casp-3 showed an overall similar expression pattern. Notably, the 20α-HSD and Casp-3 proteins were lowest at 1.5 μg/ml supplemented with 20α-HSD, with higher levels in the cytosol than in the cytoplasm. These results suggest that 20α-HSD plays a role in maintaining normal pregnancy, particularly by regulating the progesterone concentrations during luteal cell development. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to verify the action of bioactive compounds from Brazilian plants on the leader genes involved in the SARS-CoV-2 pathway. The main human genes involved were identified in GeneCards and UNIPROT platforms, and an interaction network between leader genes was established in the STRING database. To design chemo-biology interactome networks and elucidate the interplay between genes related to the disease and bioactive plant compounds, the metasearch engine STITCH 3.1 was used. The analysis revealed that SMAD3 and CASP3 genes are leader genes, suggesting that the mechanism of action of the virus on host cells is associated with the molecular effects of these genes. Furthermore, the bioactive plant compounds, such as ascorbate, benzoquinone, ellagic acid, and resveratrol was identified as a promising adjuvant for the treatment inhibiting CASP3-mediated apoptosis. Bioactive plant compounds were verified as the main pathways enriched with KEGG and related to viral infection, assessments/immune/infections, and cell proliferation, which are potentially used for respiratory viral infections. The best-ranked molecule docked in the CASP3 binding site was rutin, while the SMAD3 binding site was resveratrol. In conclusion, this work identified several bioactive compounds from Brazilian plants showing potential antiviral functions that can directly or indirectly inhibit the new coronavirus.

Background and Objectives: Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes cognitive impairment. The Aim of this Study: Was to evaluate microvesicles (MVs) and melatonin effects on mitochondrial biogenesis and apoptosis in an experimental model of Alzheimer's disease in rats Methods: Forty-five female rats were divided randomly (9 rats in each group) intoGpI (control) and experimental groups, which included: GpII (AD), GpIII (AD+MVs), GpIV (AD+melatonin), GpV (AD+MVs+melatonin). Induction of AD was done by a single intraperitoneali.p injection of lipopolysaccharide (LPS) of 0.8mg/kg. One week after the AD induction, the treated groups received a single i.p injection of MVs at a dose of 0.2mg/kg or melatonin by i.p injection of 10mg/kg once daily for three weeks or combined therapy of both. When the experiment was over, Y-maze & open field tests were used to assess the cognitive functions. The hippocampus was subjected to histological and immunohistochemical studies for assessment of the morphological changes. Besides, biochemical investigations were performed for AD pathogenesis, mitochondrial biogenesis, inflammatory mediators, and apoptosis. Results: The AD modeling group demonstrated impaired cognitive function, a significant increase in AD markers; Aβ plaques deposition in Congo-red stained sections and the levels of Aβ-42 and p-tau protein, increased apoptotic markers; Casp-3 positive immunostaining and Cyt-c level, a significant reduction in mitochondrial biogenesis markers; gene expressions of PGC-1α, Nrf-2, TFAM and Sirt-1, affection of the brain energy metabolism represented by the AMPK level. Besides, the IL-6 level increased significantly. The therapy with MVs, melatonin, or combined therapy had a curative role against AD with the best results in the combined therapy group. Conclusion: Combined therapy with MVs and melatonin was superior to single therapy for AD. [ABSTRACT FROM AUTHOR]

Hector Katifelis,1 Iuliia Mukha,2 Penelope Bouziotis,3 Nadiia Vityuk,2 Charalampos Tsoukalas,3 Andreas C Lazaris,4 Anna Lyberopoulou,1 George E Theodoropoulos,5 Efstathios P Efstathopoulos,6 Maria Gazouli1,6 1Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2Chuiko Institute of Surface Chemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 3Radiochemical Studies Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Athens, Greece; 4 1st Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece; 5 1st Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 6 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceCorrespondence: Maria Gazouli Email mgazouli@med.uoa.grPurpose: To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor’s metastatic potential and the underlying molecular mechanism.Subjects and Methods: Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively.Results: In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels.Conclusion: Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.Keywords: nanoparticles, cancer, SCID mice, TRAIL, Casp-3

Renal ischemia–reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.

Renal ischemia–reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Thermal injury may lead to multiple organ dysfunction through release of proinflammatory mediators and reactive oxygen radicals. This study investigated the effects of thermal injury on remote organs of rats and the possible protective effect of lutein. Thermal trauma was induced in the back of rats by exposing them to 90 °C bath for 10 s. Rats were sacrificed 48 h after burn, and blood samples were collected to monitor liver and kidney functions. Tissue samples from liver, kidneys, and lungs were taken for studying oxidative stress parameters, gene expressions of TNF-α and Casp-3, besides histopathological examination. Skin scald injury caused significant elevations of liver and kidney function biomarkers in the serum. In tissue samples, increments of MDA, GPx, and 8-OHdG were recorded while GSH level and the activities of CAT and SOD were suppressed. The expressions of TNF-α and caspase-3 mRNA were increased, and histopathological results revealed remote organ injury. Oral administration of lutein (250 mg/kg) resulted in amelioration of the biochemical and molecular changes induced by burn as well as the histopathological alterations. According to the findings of the present study, lutein possesses anti-oxidant, anti-inflammatory, and anti-apoptotic effects that protect against burn-induced damage in remote organs. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE. [ABSTRACT FROM AUTHOR]