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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.

To evaluate the antitumor efficacy of Ag Au Trp NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor's metastatic potential and the underlying molecular mechanism. Ag Au Trp NPs 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 Ag Au Trp NPs 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. In the 4T1 tumor-bearing SCID mice, Ag Au Trp NPs 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. Based on our results, Ag Au Trp NPs express anti-tumor and anti-metastatic effects in vivo. Ag Au Trp NPs 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.

Background: Diabetes seems to be associated with increased inflammation and induced apoptosis in several tissues. Urtica dioica and Lamium album have shown to possess a variety of beneficial properties like anti-inflammatory effects. In this experimental study, we tried to evaluate the effects of U. dioica and L. album extracts on the expression level of cyclooxygenase-2 (COX-2; as an inflammation marker) and caspase-3 (CASP-3; as an apoptotic marker) in the liver and kidney tissues of diabetic rats. Methods: Thirty-two male Wistar rats were randomly allocated to four groups: normal control, diabetic control, diabetic treated with U. dioica (100 mg/kg/daily), and diabetic treated with L. album (100 mg/kg/daily) for 28 days. At the end of the study, liver and kidney tissues were harvested and mRNA expression level of COX-2 and CASP-3 was determined by real-time PCR technique. Also, serum glucose was measured. Results: Liver COX-2 mRNA in diabetic rats was significantly higher than normal control rats (P=0.02). However, U. dioica and L. album caused significant decrease in mRNA expression of liver COX-2 in diabetic rats (P=0.015 and P=0.03, respectively). Also, in diabetic rats treated with both extracts, serum glucose was remarkably lower than diabetic control rats (P<0.0001 and P<0.01, respectively). Conclusion: It appears that U. dioica and L. album might decrease liver damage by decreasing the inflammatory effects of COX-2 in streptozocin-induced diabetic rats. Since these plant extracts may influence diabetes by several mechanisms, further research in this field is warranted.

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.

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.

Ocular squamous cell carcinoma represents the most prevalent form of cancer in cattle and exerts a deleterious effect on animal welfare and breeders. This study sought to elucidate the relationship between DNA damage and apoptosis with the aim of advancing our understanding of the pathogenesis of the disease. Nine bovine tissue samples with suspected ocular squamous cell carcinoma (OSCC) were examined histopathologically and immunohistochemically. The taken tissue samples, in histopathological examinations by haematoxylin‐eosin (HE), staining revealed the presence of neoplastic cells exhibiting various grades of differentiation. It observed the presence of polygonal or ovoid‐shaped cells with hyperchromatic nuclei and vesicular cytoplasm, as well as mitotic figures and bizarre giant cells. Islets and caudal extensions of the tumour cells were observed to contain keratin deposits. Immunohistochemical staining of OSCC tissues was performed using γ‐H2AX for DNA double‐strand breaks, 8‐OHdG for DNA oxidation and CASP‐3 biomarkers for nuclear apoptosis. The immunohistochemical examination demonstrated that the expression of 𝛾‐H2AX and 8‐OHdG was markedly elevated, while CASP‐3 expression was relatively diminished in aggressive tumours. In contrast, the opposite was observed in low‐grade tumours. This study is the first to report DNA double‐stranded breaks in eye cancers, and it has also shown that DNA helix breaks and guanine oxidation are effective in cancer pathogenesis. It has also been determined that apoptotic defence reactions due to DNA damage are reduced. In light of these findings, we made a significant contribution to the development of BOSCC carcinogenesis. This is the first study to report an increase in double‐stranded DNA breaks in BOSCC, an important tumoural disease of cattle. In this study, where an increase in DNA oxidation was also shown, we determined that apoptotic defence reactions were reduced, contributing to the pathogenesis.

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.

Aim:To identify potential prognostic biomarkers and uncover new mechanisms underlying hepatocellular carcinoma (HCC).Background:HCC is a prevalent and fatal malignancy originating from hepatic cells, with a consistently rising incidence in recent decades. Objective: To identify potential prognostic biomarkers, specifically focusing on the role of PAK1-interacting protein 1 (PAK1IP1), and to uncover novel mechanistic insights in HCC.Methods:HCC-related datasets (GSE45267 and GSE49515) and data from The Cancer Genome Atlas (TCGA) were retrieved for the analysis of differentially expressed genes (DEGs). The common DEGs were subsequently subjected to weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI), risk model, expression, survival, and prognostic nomogram to determine key genes associated with HCC. Further, the key gene was analyzed using clinical feature analysis, immunoassay, and cell experiments to investigate its exact role in HCC.Results:Based on the above comprehensive analysis, we targeted the key gene PAK1IP1 with a good prognostic value in HCC. PAK1IP1 showed a remarkably higher increase in tumor samples than in normal samples, which might be related to immune cell infiltration in liver cancer. It was up-regulated in HCC cells, and its knockdown could suppress HCC proliferation and migration. Besides, enzyme-linked immunosorbent assay (ELISA) showed that PAK1IP1 could regulate lipopolysaccharide (LPS)—induced pyroptosis of HCC cells. Knocking down PAK1IP1 could lead to increased expression of caspase 3 (CASP-3), gasdermin E (GSDME)-N, cleaved caspase-1, and gasdermin-D (GSDMD)-N in HCC cells, inducing pyroptosis, thereby inhibiting the development of HCC.Conclusion:To summarize, PAK1IP1 was identified as a promising prognostic biomarker, and the knockdown of PAK1IP1 can induce pyroptosis to suppress HCC development, which sheds new light on HCC tumorigenesis.

An electronic cigarette (e-cigarette) is initially marketed as an assistant product to quit smoking or limit its use. However, recent studies suggest the opposite, describing it as a product that lacks adequate quality and user safety. The present study aimed to investigate the effect of e-cigarette flavoring agent (cinnamon flavor) on the neural retina development of chick embryos and apoptosis induction after the early and late apoptosis stages by quantitative detection of gene expression CASP-3 at both embryonic days E9 and E17. Fertilized chicken eggs were divided into two groups: control and treatment, and each group included two embryonic days; E9 and E17. For each treatment stage, two dosages of the treatment were applied, 2% and 5%. The neural retinas were dissected from the sclera and retinal pigment epithelium for subsequent RNA extraction and histological examination. This study indicated that aerosol of the subtle cinnamon flavor e-liquid causes downregulated expression of CASP3 in neural retina development. In addition, the hematoxylin and eosin (H&E)-stained sections showed multiple structural changes in the retinal layers and evidence of apoptotic cell death. Cell death was visible and abundant in E9, and E17 concludes that flavor vapor condensate treatment caused neuronal cell death. CASP-3 was downregulated, which indicates that cell death occurred independently of CASP-3.