Effective Anticancer Potential of a New Sulfonamide as a Carbonic Anhydrase IX Inhibitor Against Aggressive Tumors.

This study examines efficiency of a newly synthesized sulfonamide derivative 2-bromo-N-(4-sulfamoylphenyl)propanamide (MMH-1) on the inhibition of Carbonic Anhydrase IX (CA IX), which is overexpressed in many solid tumors including breast cancer. The inhibitory potential of MMH-1 compound against its four major isoforms, including cytosolic isoforms hCA I and II, as well as tumor-associated membrane-bound isoforms hCA IX and XII, was evaluated. To this context, the cytotoxic effect of MMH-1 on cancer and normal cells was tested and found to selectively affect MDA-MB-231 cells. MMH-1 reduced cell proliferation by holding cells in the G0/G1 phase (72 %) and slowed the cells' wound healing capacity. MMH-1 inhibited CA IX under both hypoxic and normoxic conditions and altered the morphology of triple negative breast cancer cells. In MDA-MB-231 cells, inhibition of CA IX was accompanied by a decrease in extracellular pH acidity (7.2), disruption of mitochondrial membrane integrity (80 %), an increase in reactive oxygen levels (25 %), and the triggering of apoptosis (40 %). In addition, the caspase cascade (CASP-3, -8, -9) was activated in MDA-MB-231 cells, triggering both the extrinsic and intrinsic apoptotic pathways. The expression of pro-apoptotic regulatory proteins (Bad, Bax, Bid, Bim, Cyt-c, Fas, FasL, TNF-a, TNF-R1, HTRA, SMAC, Casp-3, -8, P21, P27, and P53) was increased, while the expression of anti-apoptotic proteins, apoptosis inhibitor proteins (IAPs), and heat shock proteins (HSPs) (Bcl-2, Bcl-w, cIAP-2, HSP27, HSP60, HSP70, Survivin, Livin, and XIAP) was decreased. These results propose that the MMH-1 compound could triggers apoptosis in MDA-MB-231 cells via the pH/MMP/ROS pathway through the inhibition of CA IX. This compound is thought to have high potential and promising anticancer properties in the treatment of aggressive tumors.

A mixed-apoptotic effect of Jurinea mesopotamica extract on prostate cancer cells: a promising source for natural chemotherapeutics.

This research investigates the potential use of Jurinea mesopotamica Hand.-Mazz. (Asteraceae) in cancer treatment. In this study, a plant extract was prepared using all parts of J. mesopotamica, and its effect on the proliferation of cancer and normal cells was tested using the MTT method. It was found to have a selective cytotoxic effect on prostate cancer cells, with the lowest IC50 (half-maximal inhibitory concentration) of 10µg/mL found in the butanol extract (JMBE). The extract suppressed the proliferation of prostate cancer cells (67 %), disrupted organelle integrity (49 %), increased reactive oxidative stress (66 %), and triggered cell death (51 %). In addition, apoptotic gene expressions and protein levels increased, and the profile of amino acids related to energy metabolism was elevated. Based on LC-MS/MS results, the plant contained higher levels of flavonoids, including isoquercitrin, cosmosiin, astragalin, nicotiflorin, luteolin, and apigenin. These results suggest that J. mesopotamica has a selective effect on prostate cancer due to its high flavonoid content and might be a promising natural alternative for cancer treatment.

Expression Analysis of the Small GTP-Binding Protein Rac in Pterygium

Objectives: To determine the roles of small GTP-binding proteins Rac1, Rac2, and Rac3 expression in pterygial tissue and to compare these expressions with normal conjunctival tissue. Materials and Methods: Seventy-eight patients with primary pterygium were enrolled. Healthy conjunctival graft specimens obtained during pterygium surgery were used as control tissue. The real-time polymerase chain reaction method on the BioMark HD dynamic array system was utilized in genomic mRNA for the gene expression analysis. Protein expressions were analyzed using western blot and immunohistochemical methods. Results: RAC1, RAC2, and RAC3 gene expressions in pterygial tissues were not markedly elevated when compared to the control specimens (p>0.05). As a very low level of RAC1 gene expression was observed, further protein expression analysis was performed for the Rac2 and Rac3 proteins. Western blot and immunohistochemical analysis of Rac2 and Rac3 protein expression revealed no significant differences between pterygial and healthy tissues (p>0.05). Conclusion: This is the first study to identify the contribution of Rac proteins in pterygium. Our results indicate that the small GTP-binding protein Rac may not be involved in pterygium pathogenesis.

Investigation of the effect of vitamin K1 prophylaxis on newborn screenings tests in newborns.

Background: Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K1. To investigate the interference effect of vitamin K1 on neonatal screening tests and to raise awareness of erroneous measurements. Methods: Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared. Results: In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05). Conclusions: Heel blood samples may yield false results due to vitamin K1 administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.

LC-MS/MS and GC-MS profiling, antioxidant, enzyme inhibition, and antiproliferative activities of Thymus leucostomus H ausskn. & V elen. extracts.

The chemical composition as well as antioxidant, antiproliferative, and enzyme inhibition activities of extracts from aerial parts of Thymus leucostomus H ausskn. & V elen. obtained with hexane, methanol, and water were evaluated. Results showed that the methanol extract had significantly (p < 0.05) the highest total phenolic content (TPC; 107.80 mg GAE/g) and total flavonoids content (TFC; 25.21 mg RE/g) followed by the aqueous extract (102.72 mg GAE/g and 20.88 mg RE/g, respectively). LC-MS/MS-guided profiling of the three extracts revealed that rosmarinic acid (34.8%), hesperetin (42.9%), and linoleic acid (18%) were the dominant compounds in the methanol, aqueous and hexane extracts, respectively. GC-MS analysis of the hexane extract showed that É£-sitosterol (29.9%) was the major constituent. The methanol extract displayed significantly (p < 0.05) the highest Cu++ , Fe+++ , and Mo(VI) ions scavenging and reducing properties while the aqueous extract exerted significantly (p < 0.05) the highest metal chelating power (42.51 mg EDTAE/g). Both the hexane and methanol extracts effectively inhibited the acetylcholinesterase enzyme (2.63 and 2.65 mg GALAE/g, respectively) while the former extract exerted significantly (p < 0.05) the highest butyrylcholinesterase (2.32 mg GALAE/g), tyrosinase (19.73 mg KAE/g), and amylase (1.16 mmol ACAE/g) inhibition capacity. The aqueous extract exhibited the best glucosidase inhibition property (0.49 mmol ACAE/g). The methanol and hexane extracts exerted a higher cytotoxic effect on HT-29 (IC50 : 8.12 µg/mL) and HeLa (IC50 = 8.08 µg/mL) cells, respectively. In conclusion, these results provide valuable insight into the potential use of T. leucostomus bioactive extracts in different pharmaceutical applications.

Protective Effects of Fuziline on Dobutamine-Induced Heart Damage in Mice.

INTRODUCTION: Fuziline is one of the many antioxidants currently being tested to treat cardiac damage. In our study, histopathological and biochemical effects of fuziline were investigated in mice with dobutamine-induced heart damage in vitro. METHODS: Thirty-two adult male BALB/c mice, average weight of 18-20 g, were randomly divided into four groups - Group 1 (sham, n=8), Group 2 (control, dobutamine, n=8), Group 3 (treatment 1, dobutamine + fuziline, n=8), and Group 4 (treatment 2, fuziline, n=8). Biochemical parameters and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were measured. Interleukin 1 beta (IL-1ß), NLR family, pyrin domain containing protein 3 (NLRP3), 8-hydroxy-deoxyguanosine (8-OHDG), gasdermin D (GSDMD), and galectin 3 (GAL-3) levels were analyzed by enzyme-linked immunosorbent assay method, and histopathological examination of heart tissues was performed. RESULTS: When dobutamine + fuziline and fuziline groups were compared, troponin-I (P<0.05), NLRP3 (P<0.001), GSDMD (P<0.001), 8-OHDG (P<0.001), IL-1ß (P<0.001), and GAL-3 (P<0.05) were found to be statistically significant. TOS level was the highest in the dobutamine group (P<0.001) and TAS level was the highest in the fuziline group (P<0.001). OSI level was statistically significant between the groups (P<0.001). In histopathological examination, focal necrosis areas were smaller in the dobutamine + fuziline group than in the dobutamine group, and cardiac myocytes were better preserved. CONCLUSION: Fuziline markedly reduced cardiac damage and pyroptosis in mice with dobutamine-induced heart damage by lowering the levels of GSDMD, 8-OHDG, IL-1ß, and GAL-3. It also prevented necrosis of cardiac myocytes in histopathological evaluation.

Cardioprotective Effect of Pistacia vera L. (Green Pistachio) Hull Extract in Wistar Albino Rats with Doxorubicin-Induced Cardiac Damage.

BACKGROUND: Pistacia vera L. (green pistachio) has been shown to increase antioxidant capacity and protect against cardiovascular diseases and cancer. This study investigated the protective effect of the Pistacia vera L. hull in rats with experimental cardiac damage induced by doxorubicin. METHODS: Sixty adult Wistar albino rats were randomly divided into 5 groups (n = 12). Sham, doxorubicin, doxorubicin + Pistacia vera L. extract 50 mg/kg, doxorubicin + Pistacia vera L. extract 100 mg/kg, and Pistacia vera L. extract 100 mg/kg. Biochemistry parameters, total antioxidant status, total oxidant status, oxidative stress index, 8-hydroxydeoxy guanosine, and caspase 3/7 values were measured in serum samples. Excised heart tissues were examined histopathologically. RESULTS: The groups were statistically significantly different in 8hydroxydeoxy guanosine, caspase 3/7, total antioxidant status, total oxidant status, oxidative stress index, and basal biochemical parameter values (P <.05, P <.001). In group II, 8-hydroxydeoxy guanosine, caspase 3/7, and total oxidant status values increased while the total antioxidant status value decreased (P <.001). In the treatment groups (group III and group IV), 8-hydroxydeoxy guano sine and caspase 3/7 values decreased compared to group II (P < .001). While total oxidant status and oxidative stress index values decreased in the treatment groups, total antioxidant status values increased (P <.001). The histopathological examination of the heart revealed fewer areas of focal necrosis in the treatment groups compared to group II. CONCLUSION: In this study, the cardioprotective effect of Pistacia vera L. hull extract was investigated in vivo. It was shown that Pistacia vera L. hull extract reduced apoptosis and deoxyribonucleic acid damage in the face of cardiac damage and had antioxidant activity. Future studies will increase our knowledge on this subject.

Local myelin damage in the hippocampus fluctuates gut microbiome profile and memory.

The concept of the gut-brain axis has focused research on how gut dysbiosis affects myelin biology in the brain. However, this axis has not been tested to determine whether it conveys the effects of myelin damage on the gut microbiome profile. Therefore, we aimed to investigate how myelin biology is correlated with gut microbiome profile. The impact of local myelin damage in the hippocampus on gut microbiome profile was investigated with 16S rRNA metagenomic sequence and molecular analysis of myelin biology-associated proteins, and its reflections on memory performance were tested with behavioral tests. Local myelin damage in the hippocampus triggered severe gut dysbiosis, p < .05, changed memory performance, p < .05, and deviated emotional responses. Moreover, myelin treatment with clemastine improved gut dysbiosis and behavioral deviations. Our study provides animal-based evidence on the direct interaction between glial biology in the hippocampus and gut microbiome profile. This study proposes a framework for generating new hypotheses bridging different systems to the gut-brain axis.

Novel zinc oxide nanoparticles of Teucrium polium suppress the malignant progression of gastric cancer cells through modulating apoptotic signaling pathways and epithelial to mesenchymal transition.

Management of gastric cancer is still challenging due to resistance to current chemotherapeutics and recurrent disease. Moreover, green- synthesized zinc oxide nanoparticles (ZnO-NPs) using natural resources are one of the most promising therapeutic agents for anticancer therapy. Here we report the facile green synthesis and characterization of ZnO-NPs from Teucrium polium (TP-ZnO-NP) herb extract and the anticancer activities of these nanoparticles on gastric cancer cells. Facile green synthesis of TP-ZnO-NP was achieved using zinc acetate dihydrate. For the characterization of TP-ZnO-NP, UV-vis spectroscopy, FTIR, SEM, XRD and EDX analyses were performed. Antiproliferative and anticancer activities of TP-ZnO-NP were explored using the HGC-27 gastric cancer cell line model. MTT cell viability and colony formation assays were used for the analysis of cell proliferation and migration. Wound healing assay was used to analyze the migration capacities of cells. Annexin V/PI double staining, DNA ladder assay, and Acridine orange/Ethidium bromide staining were performed to analyze the induction of apoptosis. qPCR was used to determine gene expression levels of apoptotic and epithelial to mesenchymal transition marker genes. The aqueous extract of TP served as both a reducing and capping agent for the successful biosynthesis of zinc oxide nanoparticles. Remarkably, synthesized TP-ZnO-NPs were found to have significant antiproliferative and anticancer activities on HGC-27 gastric cancer cells. Collectively, current data suggest that TP-ZnO-NP is a novel and promising anticancer agent for future therapeutic interventions in gastric cancer.

Protective Effects of Fuziline on Dobutamine-Induced Heart Damage in Mice

ABSTRACT Introduction: Fuziline is one of the many antioxidants currently being tested to treat cardiac damage. In our study, histopathological and biochemical effects of fuziline were investigated in mice with dobutamine-induced heart damage in vitro. Methods: Thirty-two adult male BALB/c mice, average weight of 18-20 g, were randomly divided into four groups - Group 1 (sham, n=8), Group 2 (control, dobutamine, n=8), Group 3 (treatment 1, dobutamine + fuziline, n=8), and Group 4 (treatment 2, fuziline, n=8). Biochemical parameters and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were measured. Interleukin 1 beta (IL-1β), NLR family, pyrin domain containing protein 3 (NLRP3), 8-hydroxy-deoxyguanosine (8-OHDG), gasdermin D (GSDMD), and galectin 3 (GAL-3) levels were analyzed by enzyme-linked immunosorbent assay method, and histopathological examination of heart tissues was performed. Results: When dobutamine + fuziline and fuziline groups were compared, troponin-I (P<0.05), NLRP3 (P<0.001), GSDMD (P<0.001), 8-OHDG (P<0.001), IL-1β (P<0.001), and GAL-3 (P<0.05) were found to be statistically significant. TOS level was the highest in the dobutamine group (P<0.001) and TAS level was the highest in the fuziline group (P<0.001). OSI level was statistically significant between the groups (P<0.001). In histopathological examination, focal necrosis areas were smaller in the dobutamine + fuziline group than in the dobutamine group, and cardiac myocytes were better preserved. Conclusion: Fuziline markedly reduced cardiac damage and pyroptosis in mice with dobutamine-induced heart damage by lowering the levels of GSDMD, 8-OHDG, IL-1β, and GAL-3. It also prevented necrosis of cardiac myocytes in histopathological evaluation.

Antioxidant Actions of Thymoquinone, Silymarin, and Curcumin on Experimental Aortic Ischemia-Reperfusion Model in Wistar Albino Rats

ABSTRACT Introduction: Medical improvements are needed to prevent ischemia-reperfusion injury in thoracoabdominal aortic surgery. The aim of this study was to determine the antioxidant effects of thymoquinone, silymarin, and curcumin against ischemia-reperfusion injury associated with abdominal aorta. Methods: Twenty-five Wistar albino rats were included in the study. Sham, control, and treatment (thymoquinone, silymarin, and curcumin) groups were set in equal numbers. Ischemia-reperfusion was applied by clamping (120 minutes) and de-clamping (60 minutes) the infrarenal aorta of all groups, except the sham group. Before reperfusion, thymoquinone, silymarin, and curcumin were given intraperitoneally to the treatment groups. After reperfusion, blood samples were taken from the right ventricle. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were studied in serum samples and histopathological examination was performed on the gastrocnemius muscle. Results: There was a significant difference in TOS and OSI values between the control and sham groups. Both values were found higher in the control group than in the sham group (P<0.05). OSI values were found to be lower in the thymoquinone group compared to the control group (P<0.05). All three parameters were found to be lower in the silymarin group than in the control group (P<0.05). TAS and TOS levels were found to be higher in the curcumin group than in the control group (P<0.05). There was no histopathological difference between the groups. Conclusion: Silymarin and thymoquinone administration decreases oxidative stress in experimental aortic ischemia-reperfusion injury. Antioxidant effect of curcumin was lower than silymarin and thymoquinone.

Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells.

BACKGROUND: Many chemotherapeutic drugs used in cancer treatment have anticancer properties by inducing reactive oxygen species (ROS). However, the same effect occurs in normal cells, limiting the availability of these drugs. Therefore, studies on the detection of new herbal anticancer agents that have selective effects on cancer cells are of great importance. The aim of this study is to investigate the metabolite profile of Cedrus libani tar and its mechanism of anticancer effect on colon cancer cells. METHODS AND RESULTS: Effect of cedar tar on cells (12 cancers and 5 normal cell lines) viability was determined by MTT, apoptosis induction was determined by Annexin-V, ROS and MMP determined by flow cytometry assay. Cleaved caspase-8, 9 and Ɣ-H2AX expression determined by western blot. Apoptotic and antioxidant genes expression level determined by qPCR. Metabolite profiling was performed with LC-MS/MS and GC-MS. Cedar tar showed the highest cytotoxic effect among cancer cells in colon cancer (HCT-116, IC50: 30.4 µg/mL) and its toxic effect on normal cells (HUVEC, IC50: 74.07 µg/mL) was less than cancer cell. Cedar tar increases ROS production in colon cancer cells. The metabolite profile of the cedar tar contains high amounts of metabolites such as fatty acids mainly (Duprezianene, Himachalene and Chamigrene), phenolic compounds (mostly Coumarin, p-coumaric acid, Vanillic acid and tr-Ferulic acid etc.) and organic acids (mainly 3-oh propanoic acid, 2-oh butyric acid and 3-oh isovaleric acid etc.). CONCLUSION: As a result, it has been found that cedar tar has the potential to be used in the treatment of colon cancer.

Antioxidant Actions of Thymoquinone, Silymarin, and Curcumin on Experimental Aortic Ischemia-Reperfusion Model in Wistar Albino Rats.

INTRODUCTION: Medical improvements are needed to prevent ischemia-reperfusion injury in thoracoabdominal aortic surgery. The aim of this study was to determine the antioxidant effects of thymoquinone, silymarin, and curcumin against ischemia-reperfusion injury associated with abdominal aorta. METHODS: Twenty-five Wistar albino rats were included in the study. Sham, control, and treatment (thymoquinone, silymarin, and curcumin) groups were set in equal numbers. Ischemia-reperfusion was applied by clamping (120 minutes) and de-clamping (60 minutes) the infrarenal aorta of all groups, except the sham group. Before reperfusion, thymoquinone, silymarin, and curcumin were given intraperitoneally to the treatment groups. After reperfusion, blood samples were taken from the right ventricle. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were studied in serum samples and histopathological examination was performed on the gastrocnemius muscle. RESULTS: There was a significant difference in TOS and OSI values between the control and sham groups. Both values were found higher in the control group than in the sham group (P<0.05). OSI values were found to be lower in the thymoquinone group compared to the control group (P<0.05). All three parameters were found to be lower in the silymarin group than in the control group (P<0.05). TAS and TOS levels were found to be higher in the curcumin group than in the control group (P<0.05). There was no histopathological difference between the groups. CONCLUSION: Silymarin and thymoquinone administration decreases oxidative stress in experimental aortic ischemia-reperfusion injury. Antioxidant effect of curcumin was lower than silymarin and thymoquinone.

miR-320a promotes p53-dependent apoptosis of prostate cancer cells by negatively regulating TP73-AS1 invitro.

TP73 antisense RNA 1 (TP73-AS1) is an oncogenic long non-coding RNA that is activated in several types of cancers. It has been shown that the activity of TP73-AS1 is controlled by several miRNAs, but post-transcriptional mechanisms that regulate TP73-AS1 activity in prostate cancer remain highly elusive. Accordingly, in the present study, we aimed to determine the miRNAs that are involved in the regulation of TP73-AS1 in prostate cancer and to show the effects of these molecules on the malignant proliferation of prostate cancer cells. Remarkably, colony formation and cell migration were suppressed while cell cycle arrest and apoptosis were induced in prostate cancer cells overexpressing miR-200a and miR-320a. miR-200a and miR-320a were found to be upregulated in TP73-AS1 suppressed prostate cancer cells. Also, TP73-AS1 was shown to be downregulated following miR-200a and miR-320a overexpression. However, overexpression of miR-320a had no significant effect on the expression of TP73. Further analysis revealed that miR-320a induces p53-dependent apoptosis. Consequently, our findings indicate that miR-320a induces p53-dependent apoptosis by negatively regulating TP73-AS1 long non-coding RNA.

Silencing of TP73-AS1 impairs prostate cancer cell proliferation and induces apoptosis via regulation of TP73.

BACKGROUND: Prostate cancer is a malignant disease that severely affects the health and comfort of the male population. The long non-coding RNA TP73-AS1 has been shown to be involved in the malignant transformation of various human cancers. However, whether TP73-AS1 contributes to prostate cancer progression has not been reported yet. Accordingly, here we aimed to report the role of TP73-AS1 in the development and progression of prostate cancer and determine its relationship with TP73. METHODS AND RESULTS: TP73-AS1-specific siRNA oligo duplexes were used to silence TP73-AS1 in DU-145 and PC-3 cells. Results indicated that TP73-AS1 was upregulated whereas TP73 was downregulated in prostate cancer cells compared to normal prostate cells and there was a negative correlation between them. Besides, loss of function experiments of TP73-AS1 in prostate cancer cells strongly induced cellular apoptosis, interfered with the cell cycle progression, and modulated related pro- and anti-apoptotic gene expression. Colony formation and migration capacities of TP73-AS1-silenced prostate cancer cells were also found to be dramatically reduced. CONCLUSIONS: Our findings provide novel evidence that suggests a chief regulatory role for the TP73-TP73-AS1 axis in prostate cancer development and progression, suggesting that the TP73/TP73-AS1 axis can be a promising diagnostic and therapeutic target for prostate cancer.

Asprosin and Oxidative Stress Level in COVID-19 Patients.

BACKGROUND: The global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created great problems in healthcare systems throughout the world. Although, just like other respiratory tract viral infections, it is a disease with pathophysiological processes associated in general with cytokine production, inflammation, cell death, and redox imbalance or oxidative stress, very little is known about the pathology. Also, in recent studies, the effect of asprosin, which has an important and complex role on metabolism, on COVID-19 is unknown. The aim of this study is to determine the level of asprosin, a new hormone that has the potential to affect many metabolic pathways such as glucose metabolism, in COVID-19 patients. In addition, it is to determine whether asprosin is associated with oxidative stress in COVID-19 patients. METHODS: Blood samples were taken from 30 patients diagnosed with COVID-19 confirmed with RT-PCR test and 30 healthy control subjects. The serum asprosin level was analyzed with ELISA, and total antioxidant status (TAS) and total oxidant status (TOS) levels with colorimetric analysis. RESULTS: The asprosin and TAS levels were determined to be statistically significantly decreased in the COVID-19 patients, and the TOS and OSI levels were significantly increased. CONCLUSIONS: It can be thought that a decrease in asprosin level in COVID-19 patients causes a decrease in metabolic activity, prevents sufficient energy production in patients, and therefore oxidative stress increases in patients.

Intracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor.

Carbonic anhydrase IX (CAIX) is a hypoxia-associated transmembrane protein that is critical in the survival of cells. Because CAIX has a key role in pH regulation, its therapeutic effects have been heavily studied by different research laboratories. This study aims to investigate how a synthetic CAIX inhibitor triggers apoptosis in a cancer cell line, HeLa. In this regard, we investigated the effects of the compound I, synthesized as a CAIX inhibitor, on the survival of cancer cells. The compound I inhibited the proliferation of the CAIX+ HeLa cells, kept the cells in G0/G1 phase (74.7%) and altered the cells morphologies (AO/EtBr staining) and the nuclear structure (γ-H2AX staining). CAIX inhibition triggered apoptosis in HeLa cells with a rate of 47.4%. According to the expression of mediator genes (CASP-3, -8, -9, BAX, BCL-2, BECLIN, LC3), the both death pathways were activated in HeLa cells with the inhibition of CAIX with the compound I. The compound I was also determined to affect the genes and proteins that have a critical role in the regulation of apoptotic pathways (pro casp-3, cleaved casp-3, -8, -9, cleaved PARP and CAIX). Furthermore, CAIX inhibition caused changes in pH balance, disruption in organelle integrity of mitochondria, and increase intracellular reactive oxygen level of HeLa cells. Taken together, our findings suggest that CAIX inhibition has a potential in cancer treatment, and the compound I, a CAIX inhibitor, could be a promising therapeutic strategy in the treatment of aggressive tumours.

The relationship among noise, total oxidative status and DNA damage.

PURPOSE: Noise is one of the major environmental health problems and is defined as any unpleasant sound. It was shown that prolonged exposure to noise was associated with progress of diseases. There is no study evaluating the effect of noise on the oxidative parameters of Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS) and DNA damage. AIM: This study aimed to evaluate the effect of noise on TOS, TAC and DNA damage. METHODS: In this study, we included 100 textile factory workers affected by noise as a noise group, and 56 healthy volunteers employed as office workers in our hospital who were not exposed to noise as the control group. Blood samples were obtained from both the groups. Oxidative Stress (OS) was measured by Oxidative stress index (OSI), TOS and TAC. The DNA damage level was measured by 8-Hydroxydeoxyguanosine (8-OHdG). RESULTS: 8-OHdG (21.8 ± 12.0 vs. 14.7 ± 5.6 pg/ml, p = 0.001),TOS (14.1 ± 2.5 vs. 10.9 ± 1.5 mol H2O2 equivalent/l, p < 0.001), TAC (0.96 ± 0.19 vs. 1.54 ± 0.28 Trolox equivalent/l, p < 0.001) and OSI (1.52 ± 0.37, etc. 0.76 ± 0.35 arbitrary units, p < 0.001) were significantly higher in noise group compared to control group. Linear regression analysis showed that noise was the independent predictor of DNA damage (ß = 0.310, p < 0.001). CONCLUSION: In this study, we showed that TOS and DNA damage were significantly higher in subjects exposed to noise when compared with subjects of the control group. Noise was the only independent predictor of the DNA damage. Therefore, early detection of DNA damage and increased OS, early corrective measures may delay the development and progression of diseases such as hypertension, arrhythmias.

miR-19a and miR-421 target PCA3 long non-coding RNA and restore PRUNE2 tumor suppressor activity in prostate cancer.

BACKGROUND: Prostate cancer antigen 3 (PCA3) is the most promising diagnostic biomarker for the differential diagnosis of prostate cancer identified to date. As a dominant-negative oncogene, PCA3 negatively regulates the expression of tumor suppressor PRUNE2 (a human homolog of the Drosophila prune gene) gene. Although interaction between PCA3-PRUNE2 was clearly reported, the precise mechanism how PCA3 is upregulated in prostate cancer remained highly elusive. Accordingly, here we aimed demonstrate the role of microRNAs in PCA3 upregulation and interplay between these miRNAs and PCA3-PRUNE2 axis. METHODS AND RESULTS: We evaluated expression of PCA3, PRUNE2 and miRNAs by quantitative reverse transcription polymerase chain reaction. Overexpression and silencing of miRNAs were achieved by synthetic miRNA mimics and inhibitors, respectively. Colony formation, migration, apoptosis, and cell cycle assays were performed to reveal the effects of miRNA modulation. We identified that PCA3 expression was significantly downregulated in both prostate cancer tissues and cells and inversely correlated with the expressions of miR-19a and miR-421. Restoring the functions of miR-19a and miR-421 by miRNA mimics significantly downregulated the expression of PCA3 and promoted apoptosis and cell cycle blockade and interfered with the proliferation and migration in prostate cancer cells. Conversely, silencing the expressions of these miRNAs yielded the opposite effect. CONCLUSIONS: Collectively, our results uncover a previously unrecognized novel mechanism on PCA3 upregulation in prostate cancer and proved that miR-19a and miR-421 might be responsible for the increased expression of PCA3, indicating that both miRNAs might be novel candidates for prostate cancer diagnosis and therapy.

Soluble ST2 as a Potential Biomarker in Pericardial Fluid of Coronary Artery Patients

Abstract Introduction: The growth Stimulation expressed gene 2 (ST2) (or interleukin 1 receptor-like 1, also known as IL1RL1) is considered a biomarker of poor prognosis in cardiovascular diseases. The aims of this study are to investigate ST2 in the pericardial fluid (PF) of coronary artery disease patients and to contribute to the understanding of the pathophysiology of coronary artery disease. Methods: 40 patients (blood plasma and PF) who underwent coronary artery bypass surgery and 40 controls (blood plasma only) were included in this study. Soluble ST2 (sST2) level was determined by enzyme-linked ımmunosorbent assay method in plasma and PF, and sST2 gene expression was determined by quantitative real-time polymerase chain reaction (QRT-PCR) method. Results: The sST2 level was found to be 44.89 ng/ml and 390.357 ng/ml in the control and patient groups' plasma, and 223.992 ng/ml in the PF of the patient group. An increase in sST2 level was detected in the patient group compared to the control group (P<0.001). The sST2 expression in plasma was higher in the patient group than in the control group. Additionally, sST2 was more expressed in the plasma of the patient group than PF (P<0.001). Conclusion: The fact that sST2 was detected for the first time in a high level in PF showed that this biomarker was closely related with the heart and strengthened its potential to be used as a biomarker. Therefore, sST2 can contribute to the understanding of the pathophysiology of coronary artery disease.