The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats

Little is known about the effective role of Hypericum perforatum on hepatic ischemia-reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE50) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE50 significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment-control group (p < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body

Gallic acid reduces experimental colitis in rats by downregulation of cathepsin and oxidative stress

Objective: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) with common, repetitive inflammation of the colon and rectum, which is highly defined by loss of blood on colon mucosa, ulceration and acute inflammation. The present study aimed to investigate the potential protective effects of gallic acid (GA) through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model, using biochemical and histopathological parameters. Materials and Methods: The study consisted of four groups, each including seven rats, namely control group, colitis group, colitis-GA 50 mg/kg group and colitis-GA 100 mg/kg group. Colon tissue samples were analyzed for malondialdehyde (MDA), myeloperoxidase (MPO), cathepsin B and cathepsin L values. Results: Tissue MDA, MPO, cathepsin L and cathepsin B values increased significantly in colitis group (p=0.028, p=0.038, p=0.024, p=0.019, respectively). However, MDA, MPO, cathepsin L and cathepsin B values showed a significant decrease in animals with GA (at a dose of 100 mg/kg) administration in TNBS-induced colitis in rats (p=0.021, p=0.026, p=0.019, p=0.031, respectively). Colitis group was defined by the severe detriment of surface epithelium, submucosal edema and inflammatory cell infiltration. Treatment with GA significantly decreased inflammatory cell infiltration. Conclusion: GA can be used as an effective agent in the treatment of colitis due to its inhibitory properties in multiple pathways and its potent antioxidant effect

Pro-inflammatory 'M1 macrophage' vs anti-inflammatory 'Hydrocortisone' a new approach to wound healing in HaCaT cells

Background and Aims: Wound healing is a process of repairing the skin that has lost its integrity through inflammation, proliferation, and remodeling. Macrophages exhibit adaptability, transitioning from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype throughout wound healing for optimal outcomes. Hydrocortisone's M2c polarization makes it a key agent for balancing M1/M2 polarization. In this study, we specifically explored the effects of M1 macrophages and hydrocortisone on cell migration and wound healing in HaCaT keratinocytes.Methods: To better understand how macrophages contribute to wound healing, we created a co-culture scratch assay model of HaCaT cells using M1-polarized macrophages derived from THP-1 cells. In addition, we administered hydrocortisone, 'an anti-inflammatory drug', to our experimental groups to compare the effects. We determined the proliferation effects of different concentrations of hydrocortisone and PMA on HaCaT cells. Then, we evaluated the effects of polarized M1 macrophages and hydrocortisone on the wound healing of HaCaT cells by scratch assay and COL1A1 mRNA gene expression levels.Results: As a result, it was determined that 100 mu M hydrocortisone increased HaCaT cell migration and COL1A1 mRNA gene expression compared to control, while M1 polarized macrophages decreased these effects negatively.Conclusion: To understand the macrophages responsible for the mechanisms of wound healing, much more study is required. Macrophages are a vital component in the healing process for wounds, and the shifting of M1/M2 in the treatment of wounds can potentially lead to the enlargement of novel treatment methods

Uncommon site of prostatic adenocarcinoma metastasis thyroid cartilage

Aim: Prostate cancer is the most common malignancy in men and tends to metastases to bone, lung, liver, pleura and adrenal glands. Herein we presented a case of prostate carcinoma with an atypical site of metastasis. Method: An 83-years-old male patient with a known diagnosis of prostate cancer and newly developed mass in the left lung was referred to fludeoxyglucose (FDG) positron emission tomography (PET)/computerized tomography (CT) and Ga-68 prostate membrane antigen (PSMA)/PET/CT. Results: FDG PET/CT demonstrated hypermetabolic mass located in apicoposterior segment of the left lung and multiple hypermetabolic metastatic lesions in skeletal system including the right side of the thyroid cartilage. Then, patient underwent Ga-68 PSMA PET/CT due to an increase in prostate-specific antigen level (12.39 ng/mL). Ga-68 PSMA PET/CT revealed PSMA accumulation in the mass located in left lung, intense PSMA uptake in the prostatic gland and increased uptake in the widespread metastatic lesions of skeletal system involving the right side of the thyroid cartilage. Conclusion: Ga-68 PSMA is a useful tool for evaluating the distant and unexpected metastases of prostate cancer. Cartilaginous tissue is a resistant site for metastasis because its rich structure of protease inhibitors prevents the destruction of extracellular matrix components. In this patient with advanced stage prostate cancer, both FDG and PSMA uptake were observed in the thyroid cartilage metastasis

Phytoestrogenic Activities of Daucane Esters from Ferulago campestris on MCF-7 Cell Lines

Introduction: Daucane sesquiterpenes are natural compounds possessing several biological activities thus being considered as good pharmacophoric models for the study of novel bioactive agents. Daucane esters are sesquiterpene compounds that are typical of Ferula and related species. Derivatives were reported from different Ferula and Ferulago species and the various natural compounds possess a common structure characterized by fused hepta- and penta- atomic rings with different hydroxylated positions that could be esterified by organic acids. Daucane obtained from roots of Ferulago campestris and Ferula glauca were previously studied as antiproliferative and antiapoptotics in human tumor cell lines. Hence, phytoestrogenic activities of daucane esters isolated from F. campestris were examined on MCF-7 cell lines using the Real-Time XCELLigence impedance analysis. Methods: Extracted and purified daucane esters tested on MCF-7 cells to measure cell growth and proliferation using real-time xCELLigence cell impedance analysis (Roche Applied Science) on disposable E-plates with 48 (16x3) wells containing integral sensor electrode arrays. This method uses impedance technology as an indicator of cell attached (1,2). Results: We tested 13 different natural daucane derivatives for the ability to interact with estrogenic receptor in a cellular model. Concentrations were selected as 6 and 25 µg/mL in order to avoid possible cytotoxic effects of the tested compounds in the assay conditions. Among the tested compounds (1-13) applied at 6 µg/mL concentrations for the assessment of MCF-7 cell proliferation after 24, 48 and 72 hours, compounds 4, 6, 7 and 9-13 exhibited significant increases in cell index (CI) values relative to controls. However, it was estimated that not all of these increases were depending on time of exposure elapsed. Conclusions: The obtained data revealed moderate effect for several of the considered daucane esters. Surprisingly the compound 12 the only compound of the series that present a free phenolic group was not active while severeal derivatives possessing more lipophylic or non aromatic ester substitutions (as compounds 4, 6, 7, 9, 11, 13) presented significant effects in the used model

Enhanced angiogenesis of human umbilical vein endothelial cells via THP-1-derived M2c-like macrophages and treatment with proteasome inhibitors 'bortezomib and ixazomib'

The leading cause of cancer-related death is lung cancer, with metastasis being the most common cause of death. To elucidate the role of macrophages in lung cancer and angiogenesis processes, we established an in vitro co-culture model of A549 or HUVEC with THP-1 cells that polarized to M2c macrophages with hydrocortisone. The proteasome inhibitors bortezomib and ixazomib were investigated for their effects on proliferation, invasion, migration, metastasis, and angiogenesis pathways. The effects of bortezomib and ixazomib on gene expression in gene panels, including crucial genes related to angiogenesis and proteasomes, were investigated after the co-culture model to determine these effects at the molecular level. In conclusion, bortezomib and ixazomib showed antiproliferative effects in both cells, as well as in M2c macrophage co-culture. M2c macrophages also increased invasion in A549 cells and both invasion and migration in HUVEC. mRNA expression upregulation, specifically in the NFKB and VEGF genes, supported the metastatic and angiogenic effects found in A549 and HUVEC with M2c macrophage co-culture. Additionally, bortezomib inhibited the VEGFB pathway in HUVEC and NFKB1 in A549 cells. The significant findings obtained as a result of this study will provide information regarding angiogenesis induced by M2 macrophages.Trkiye Bilimsel ve Teknolojik Arascedil;timath;rma Kurumu [319S088]; Scientific and Technological Research Council of Turkey (TUBITAK)This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under Grant No. 319S088