Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

It was aimed to evaluate whether gallic acid (GA) have a beneficial effect in the testicular ischemia/reperfusion injury (IRI) model in rats for the first time. Testicular malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1 protein, nuclear factor kappa B, tumor necrosis factoralpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor 6, CCAAT-enhancer-binding protein homologous protein and caspase-3 levels were determined using colorimetric methods. The oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis levels increased statistically significantly in the IRI group compared with the sham operated group (p < 0.05). GA application improved these damage significantly (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. Our findings suggested that GA may be evaluated as a protective agent against testicular IRI.

Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats.

The aim of this study was to determine the possible therapeutic effect of chlorogenic acid (CGA) on cisplatin (CDDP)-induced ovarian damage in rats. Rats were first exposed to CDDP (5 mg/kg) and then treated CGA (1.5 and 3 mg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by CDDP administration (p < 0.05). Treatments with CGA significantly alleviated these markers dose-dependently (p < 0.05). These data reveal that CGA may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue.

Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

Alpha-pinene neutralizes cisplatin-induced reproductive toxicity in male rats through activation of Nrf2 pathway.

PURPOSE: Testicular toxicity is one of the most important side effects of cisplatin (CP) therapy. Alpha-pinene (AP) is a naturally occurring monoterpene with antioxidant character in plants. Here, we aimed to evaluate the therapeutic activity of AP against CP-induced testicular toxicity by including the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway in rats. METHODS: Thirty male rats were divided into 5 groups: control, CP, CP + AP (5 and 10 mg/kg) and only AP (10 mg/kg). CP was administered intraperitoneally at a dose of 5 mg/kg on the first day, followed by three consecutive injections of AP. Serum reproductive hormone levels were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of AP on this situation were also addressed. RESULTS: Treatment with CP significantly increased OS, inflammation, ERS and apoptosis in testicular tissue. Administrations of AP resulted in an amelioration of these altered parameters. The mechanism of therapeutic effect of AP appeared to involve induction of Nrf2. Furthermore, these results were also confirmed by histological data. CONCLUSION: Results suggest that AP can exhibit therapeutic effects against CP-induced testicular toxicity. It can be concluded that AP may be a potential molecule to abolish reproductive toxicity after chemotherapy.

Evaluation of the therapeutic effects of arbutin on cisplatin-induced ovarian toxicity in rats through endoplasmic reticulum stress and Nrf2 pathway.

Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.

Gentisic acid ameliorates cisplatin-induced reprotoxicity through suppressing endoplasmic reticulum stress and upregulating Nrf2 pathway.

Reproductive toxicity is a serious side effect of cisplatin (CP) chemotherapy. Gentisic acid (GTA) is a phenolic acid with strong antioxidant properties. Here, we aimed to determine therapeutic effect of GTA against CP-induced testicular toxicity in rats for the first time. Male Sprague-Dawley rats received a single dose of CP (5 mg/kg; intraperitoneal) and treated with GTA (1.5 and 3 mg/kg; intraperitoneal; 3 consecutive days). The levels of oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis biomarkers were assessed in the testicular tissue of rats. In addition, how CP affects the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and the effect of GTA on this situation were also addressed in the testicular tissue. CP administration induced histopathological changes in testicular tissue of rats with a significant increase in OS, inflammation, ERS and apoptosis biomarkers and a decrease in antioxidant capacity and Nrf2 expression levels. Administrations of GTA resulted in an amelioration of these altered parameters. These data suggest that GTA may be a potential therapeutic agent against CP-induced testicular toxicity. Activation of the Nrf2 pathway plays a key role of this therapeutic effect of GTA.

The ameliorative effect of Primula vulgaris on cisplatin-induced nephrotoxicity in rats and quantification of its phenolic components using LC-ESI-MS/MS.

Cisplatin (CDDP) is an important chemotherapeutic agent, accumulation of which in kidney tissue causes nephrotoxicity and renal failure. The aim of this study was to evaluate, for the first time in the literature, the protective effect of dimethyl sulfoxide (DMSO) extract of Primula vulgaris leaf (PVE) against CDDP-induced nephrotoxicity in rats. The PVE content was characterized using liquid chromatography-mass spectrometry. Nephrotoxicity was induced with a single dose of CDDP (7.5 mg/kg). Thirty female Wistar-Albino rats were divided into five groups (control, DMSO, CDDP (7.5 mg/kg), CDDP + PVE (25 mg/kg), and CDDP + PVE (50 mg/kg)). Biochemical and histopathological analyses were then performed. Rutin, gallic acid, p-coumaric acid and protocatechuic acid were identified as major components of PVE. Total antioxidant status and glutathione (GSH) values increased significantly in the serum samples from the treatment group compared to the CDDP group, while blood urea nitrogen, creatinine, oxidative stress index, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total oxidant status, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CDDP group, while TNF-α, caspase-3, 8-OHdG, MDA levels and damage scores decreased significantly. In conclusion, PVE exhibited strong protective effects through its anti-apoptotic, antioxidant, and anti-inflammatory activities against nephrotoxicity and oxidative damage caused by CDDP in rats.

Protective potential of pterostilbene against cyclophosphamide-induced nephrotoxicity and cystitis in rats.

PURPOSE: Cyclophosphamide (CYP) is an antitumor drug. However, in addition to its antitumor affect, CYP can also lead to nephrotoxicity and hemorrhagic cystitis. The purpose of this study was to investigate the potential protective effects of Pterostilbene (Pte), a natural antioxidant as a resveratrol analog against CYP-induced nephrotoxicity and cystitis in rats. METHODS: Twenty-one male Sprague Dawley rats were divided into 3 equal groups. The control group and the CYP group (CYPG) received 1 ml/kg sunflower oil per day, and the CYP + Pte group (CYP + PteG) 40 mg/kg per day Pte dissolved in sunflower oil once a day via the oral route for 14 days. In addition, on day 9 of the experiment, CYPG and CYP + PteG received a single dose of 200 mg/kg CYP dissolved in saline solution, while the control group received a single dose of 10 ml/kg saline solution, via the intraperitoneal route. Bladder and kidney tissues were collected for histological and biochemical evaluations. RESULTS: Pte was observed to reduce CYP-derived increases in malondialdehyde level, total oxidant status (TOS), the oxidative stress index (OSI), and apoptosis in kidney tissues and to cause an increase in superoxide dismutase levels. It also reduced CYP-derived increases in TOS, OSI, and apoptosis in bladder tissue. Moreover, Pte also ameliorated histopathological findings associated with CYP-induced tissue damage in both the kidney and bladder. CONCLUSION: Our study findings show that Pte may exhibit a protective effect against CYP-induced nephrotoxicity and cystitis.

Vanillic acid abrogates cisplatin-induced ovotoxicity through activating Nrf2 pathway.

Although cisplatin (CDDP) is an effective anticancer agent, the ovotoxicity that can occur in female patients limits its use. Oxidative stress (OS) and inflammation are known to contribute to CDDP-induced ovotoxicity. Vanillic acid (VA) is a dietary herbal secondary metabolite with high free radical scavenging activity. It was aimed to evaluate the therapeutic effects of VA against CDDP-induced ovotoxicity in rats in this study for the first time. Ovotoxicity was achieved with a single dose of CDDP (5 mg/kg) in female rats. The therapeutic effect of VA was evaluated with 3-day administration of two different doses (5 and 10 mg/kg). While OS, inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were measured in tissue samples, the levels of reproductive hormones were determined in serum samples using colorimetric methods. The results showed that CDDP-induced nuclear factor erythroid 2-associated factor 2 (Nrf2) inhibition combined with increased OS, inflammation, ERS and apoptosis increased ovarian damage. VA treatments reversed these changes via activating Nrf2 pathway dose-dependently. In addition, histopathological findings also supported the biochemical results. VA may be a good therapeutic molecule candidate for CDDP-induced ovarian damage due to strong antioxidant and Nrf2 activator properties.

Arbutin abrogates testicular ischemia/reperfusion injury in rats through repression of inflammation and ER stress.

The aim of this study was to investigate the effects of arbutin (ARB) administration on oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis in an experimental testicular torsion/detorsion (T/D)-induced testicular injury model for the first time. A total of 24 male Sprague-Dawley rats were divided into four groups with six rats in each group: sham control, T/D, T/D+ARB (50 mg/kg) and T/D+ARB (100 mg/kg). Torsion and detorsion times were applied as 4 h and 2 h, respectively. The levels of lipid peroxidation [malondialdehyde (MDA)] and oxidative stress [total oxidant status (TOS) and total antioxidant status (TAS)] in testicular tissues were determined using colorimetric methods. The levels of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], antioxidant system [superoxide dismutase (SOD) and catalase (CAT)], pro-inflammatory cytokines [high mobility group box 1 (HMGB1), nuclear factor kappa B protein 65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and myeloperoxidase (MPO)], ER stress [78-kDa glucose-regulated protein (GRP78), activating transcription factor 6 (ATF6) and CCAAT-enhancer-binding protein homologous protein (CHOP)] and apoptosis (caspase-3) markers in testicular tissues were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. In the T/D group, it was determined that statistically significant increasing in the levels of oxidative stress, inflammation, ER stress and apoptosis compared with sham control group (p < 0.05). ARB administrations statistically significantly restored testicular I/R damage in a dose dependent manner (p < 0.05). In addition, it was determined that the data of histological examinations supported the biochemical results. Our findings support the hypothesis that ARB may be used as a protective agent against T/D-induced testicular damage.

Syringic acid ameliorates ischemia/reperfusion-induced testicular injury in rats via suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

PURPOSE: To investigate the possible protective role of syringic acid on torsion/detorsion-induced testicular injury using biochemical and histopathological approaches for the first time. METHODS: A total of 24 rats were divided into 4 groups: sham control, torsion/detorsion, torsion/detorsion + syringic acid (50 mg/kg and 100 mg/kg). Tissue malondialdehyde, total oxidant status and total antioxidant status levels were determined using colorimetric methods. Tissue 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1, nuclear factor kappa B protein 65, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor-6, C/EBP homologous protein and caspase-3 levels were determined using commercial enzyme-linked immunosorbent assay kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: Compared with the control group, the levels of oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis were significantly increased in the torsion/detorsion group (p < 0.05). Syringic acid administrations statistically significantly restored these damage in a dose dependent manner (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. CONCLUSION: The overall results suggest that syringic acid emerges as a potential compound for the treatment of testicular torsion and may be subject to clinical trials.

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study.

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENTWhat is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential.What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential.What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity.

An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway.

The aim of the present study was to investigate the role of Rhododendron luteum extract (RLE) in the induction of Nrf2­related oxidative stress and endoplasmic reticulum (ER) stress in human cervical cancer (HeLa) cells. The antiproliferative effect of RLE on HeLa and fibroblast cells was determined using the MTT assay. The effects of RLE on the cell cycle, apoptosis, and production of reactive oxygen species (ROS) in HeLa cells were evaluated using fluorescent probes. The mRNA expression levels of Nrf2 [and its targets glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD)], and C/EBP homologous protein (CHOP, an ER stress marker were determined using reverse transcription­quantitative polymerase chain reaction (RT-PCR). The results demonstrated that RLE exhibited a selective cytotoxic effect (2.9-fold) on HeLa cells compared to fibroblast cells. RLE arrested the cell cycle at the S phase, and induced apoptosis, ER stress, and ROS formation. In addition, RLE significantly suppressed the expression levels of Nrf2, GCLC and G6PD (0.65, 0.69, and 0.54-fold, respectively) and increased the expression of CHOP (4.48-fold) in HeLa cells at 72 h of treatment (p < 0.05). These results show that the antiproliferative effect of RLE occurs through the Nrf2 and ER stress pathways, and the results should now be supported by further in vivo studies.

circRNAs in drug resistance of breast cancer.

Breast cancer (BC) is the most common heterogeneous disease in women and one of the leading causes of cancer-related death. Surgery, chemotherapy, radiotherapy, hormone, and targeted therapy are the gold standards for BC treatment. One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics, resistance that severely limits the use and effectiveness of the drugs used for BC treatment. Therefore, it is essential to develop new strategies to improve therapeutic efficacy. Circular RNAs (circRNAs) are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5', and 3'; ends. Accumulating evidence suggests that circRNAs have a vital role in cancer development, progression, and BC resistance to chemotherapy. The purpose of this review is to discuss the biological properties of circRNAs, and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment, by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance, such as drug efflux, apoptosis dysfunction, autophagy, and DNA damage repair. CircRNAs are associated with drug resistance via ATP-binding cassette (ABC) efflux transporters, while some others by inhibition of cell apoptosis, thus leading to resistance to tamoxifen in BC cells. In contrast, others are involved in the promotion of BC cells chemoresistance by doxorubicin-induced autophagy. CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment. CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.

Reference change value and measurement uncertainty in the evaluation of tumor markers.

The use of measurement uncertainty among clinical laboratories becomes widespread. Measurement uncertainty can be reported with the result, as well as be used in certain reference change value (RCV) calculation equations. RCV is especially recommended for use in tests with a low individuality index. In our study, we calculated the measurement uncertainty of AFP, CA 125, CA 15-3, CA 19-9, CEA tumor markers with the ISO TS 20914:2019. We compared results with limits. Two Beckman Coulter DXI-800 (Minnesota, USA) autoanalysers' results were used. We calculated the RCV values using the classical Fraser method, logarithmic Lund Method, and Clinical Laboratory Standards Institute (CLSI) method as Minimal Difference (MD). We found the same permissible measurement uncertainty limit as 15.97% for all five tumor markers. The highest RCV value was found as 90% upstream for AFP test with Lund logarithmic approach, the lowest RCV value was found as 12% for CEA with MD, all other RCV results were between these two values. We do not recommend the use of MD, as values for Biological variation are not used in the MD approach. We also recommend using the logarithmic approach, although it gives higher results. There are also clinical studies on the significance of tumor markers in a follow-up that show different results. These differences may be because the studies are conducted with different systems. Therefore, each laboratory needs to calculate its own RCV values. We also recommend informing the clinicians about the tests with high measurement uncertainty.

Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models.

Six extracts were obtained from plant species Hypericum perforatum L., collected at Samsun in Turkey. The aim of this study was to examine the mechanisms of the anticancer activity of these extracts. Methanol, ethyl-acetate and hexane were used as a solvents for extraction from both branch-body part of the plant (extracts 1, 2 and 3) and from plant flowers (extracts 4, 5 and 6). The cytotoxic effects of the extracts were determined against 2D and 3D cancer cell models. Cell cycle changes of treated HeLa cells were analyzed by flow cytometry. Measurements of gene and microRNA expression levels in treated HeLa cells were done by quantitative real time PCR. Five examined extracts (2-6) exerted selective concentration-dependent cytotoxic effects on HeLa, K562, and A549 cancer cells, while the extract 1 exhibited very weak cytotoxicity. The extract 6 showed the highest intensity of cytotoxic activity. All tested extracts (2-6) demonstrated the ability to induce apoptosis in HeLa cells through activation of caspase-3. These extracts remarkably decreased gene expression levels of MMP2, MMP9, TIMP3, and VEGFA in HeLa cells. Flower extracts might have stronger effects on miR128/193a-5p/335 level changes than branch-body extracts. Hypericum perforatum extracts exerted weaker cytotoxic effects on 3D HeLa spheroids when compared with their effects on 2D monolayer HeLa cells. Taken together, results of our research may suggest the promising anticancer properties of the Hypericum perforatum extracts.

Biomarker potentials of miRNA-associated circRNAs in breast cancer (MCF-7) cells: an in vitro and in silico study.

Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related with deaths. circRNAs operate as part of competing endogenous RNAs (ceRNAs) mechanisms, which play critical roles in the different biological processes of breast cancer such as proliferation, migration, and apoptosis. The goal of the present study is to identify the potential predictive biomarker for breast cancer diagnosis in the circRNA network by in vitro and in silico analyzes. 40 miRNAs were obtained from the miRWalk database and their combinatorial target genes (potential ceRNAs) were identified with ComiR. We stated that the cancer-specific circRNA genes in MCF-7 cells using the cancer-specific circRNA (CSDC) database, and obtained the ones showing potential ceRNA activity in our previous analysis among them. Identified genes with remarkable expression differences between BCa and normal breast tissue were determined by the GEPIA database. Moreover, the Spearman correlation test in the GEPIA database was used for the statistical analysis of the relationship between DCAF7 and SOGA1, SOGA1 and AVL 9, DCAF7 and AVL 9 gene pairs. And also, DCAF7, SOGA1, and AVL9 gene expression levels were detected in MCF-7 and MCF-10A cells by RT-qPCR method. DCAF7, SOGA1, and AVL9 gene were significantly more expressed to BCa tissue and MCF-7 cells than normal breast tissue and MCF-10 A cells. And also, DCAF7 and SOGA1, SOGA1 and AVL9, DCAF7 and AVL9 genes pairs were found to be significantly correlated with BCa. These genes may be considered as potential predictive biomarkers to discriminate BCa patients from healthy persons. Our preliminary results can supply a new perspective for in vitro and vivo studies in the future.

Circulating serum miR-200c and miR-34a-5p as diagnostic biomarkers for endometriosis.

OBJECTIVE: Endometriosis is defined by the presence of endometrial glands and stroma grow in areas outside the uterus. A simple blood test for endometriosis-specific biomarkers would offer a more timely accurate diagnosis of the disease and could lead to earlier treatment intervention. Alterations in microRNA (miRNA) levels in blood may reflect changes during normal physiologic processes and have been related to several pathologic conditions, including gynecologic diseases. In the present study, we aim to evaluate the level of serum miR-34a-5p and miR-200c from women with and without endometriosis, and to explore the potential of miRNAs as reliable non-invasive biomarkers in the diagnosis of endometriosis. METHODS: Expression levels of miRNAs were performed by quantitative real-time polymerase chain reaction (qRT-PCR). Serum cancer antigen 125 (CA-125) levels were analyzed by autoanalyzer. RESULTS: miR-34a-5p expression levels were decreased and miR-200c expression levels were increased in the endometriosis patients compared to the control group. According to the areas under the ROC curve (AUC) values, miR-200c and miR-34a-5p may serve as biomarkers for the diagnosis of endometriosis. Serum miR-34a-5p and miR-200c had a sensitivity of 78.95 % and 100 % and a specificity of 49.12 % and 100 %, respectively, for the detection of endometriosis. CONCLUSION: Serum miRNAs may provide a promising opportunity for diagnosis of endometriosis. Understanding the role of circulating miRNAs will serve a better comprehension of the systemic effects of endometriosis and offer options for new treatments. It is clear that more work is needed in this area.

Circular RNAs serve as miRNA sponges in breast cancer.

Circular RNAs are a large group of non-coding RNAs with a closed-loop structure. circRNAs play significant roles in many biological processes as miRNA sponges, regulators for gene transcription, combining with RNA-binding proteins and translation of protein. Nowadays, circRNAs have become a research hotspot in the field of cancer and molecular biology. Accumulating evidences have indicated that circRNAs participate in the initiation and development of various cancers such as breast cancer. Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related deaths. The goal of the present review is to introduce biogenesis, function characteristics and types of circRNAs, and also their biological functions on breast cancer, especially as miRNA sponges. Additionally, we discuss their use as a new therapeutic target for the treatment of breast cancer.

Dorycnium pentaphyllum Extract Has Antiproliferative Effect on Human Cervix and Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.