Randomized clinical trial of astaxanthin supplement on serum inflammatory markers and ER stress-apoptosis gene expression in PBMCs of women with PCOS.

Polycystic ovarian syndrome (PCOS) is related to pro-apoptotic and pro-inflammatory conditions generated by Endoplasmic reticulum (ER) stress. This study aimed to determine the effect of Astaxanthin (ASX), as carotenoid with potent antioxidant and anti-inflammatory properties, on serum inflammatory markers, apoptotic factors and ER stress-apoptotic genes in peripheral blood mononuclear cells (PBMCs) of women with PCOS. This randomized, double-blind clinical trial included 56 PCOS patients aged 18-40. For 8 weeks, subjects were randomly assigned to one of two groups: either 12 mg ASX (n = 28) or placebo (n = 28). Real-time PCR was used to quantify gene expression associated with ER stress-apoptosis in PCOS women's PBMCs. The levels of TNF-α, IL18, IL6 and CRP were determined by obtaining blood samples from all patients before and after the intervention using Enzyme-linked immunosorbent assay (ELISA). Also, the levels of active caspase-3 and caspase-8 were detected in the PBMC by ELISA kit. Furthermore, we evaluated the efficacy of ASX on disease symptoms. Following the 8-week intervention, ASX supplementation was able to reduce the expression of GRP78 (p = 0.051), CHOP (p = 0.008), XBP1 (p = 0.002), ATF4 (0.038), ATF6 (0.157) and DR5 (0.016) when compared to the placebo. However, this decrease was not statistically significant for ATF6 (p = 0.067) and marginally significant for GRP78 (p = 0.051). The levels of TNF-α (p = 0.009), IL-18 (p = 0.003), IL-6 (p = 0.013) and active caspase-3 (p = 0.012) were also statistically significant lower in the therapy group. However, there was no significant difference in CRP (p = 0.177) and caspase-8 (p = 0.491) levels between the treatment and control groups. In our study, ASX had no significant positive effect on BMI, hirsutism, hair loss and regularity of the menstrual cycle. It appears that ASX may benefit PCOS by changing the ER stress-apoptotic pathway and reducing serum inflammatory markers; however, additional research is required to determine this compound's potential relevance.

High Anti-Müllerian Hormone Strongly Correlates with Reproductive Outcomes in Women Undergoing Assisted Reproduction.

BACKGROUND: In a retrospective cohort of 881 women with gynecologic and unexplained infertility, we aimed to study the relationship between serum AMH levels and ART outcomes. This retrospective cohort includes 881 infertile women aged 20 - 45 who underwent their first fresh autologous non-preimplantation genetic diagnosis ART cycles between 2012 and 2020. METHODS: We assessed the correlation between AMH levels and reproductive outcomes among infertile women with different causes of infertility (including endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility). RESULTS: We found a strong correlation between high AMH levels and reproductive outcomes independent of age and the cause of infertility in women undergoing ART. In all patients with gynecologic and unexplained infertility, higher AMH correlated with the improved number of oocytes (p < 0.001), MII oocytes (p < 0.001), good-quality embryos (p < 0.001), chemical pregnancy rate (p < 0.001 in women < 37; and p = 0.002 in women over 37), clinical pregnancy rate (p < 0.05), and live birth rate (p = 0.05). CONCLUSIONS: Serum AMH concentrations can be invaluable for predicting ovarian reserve and reproductive outcomes in young and advanced-age infertile patients undergoing ART. However, it should not be used as the sole predictive marker for disqualifying infertile women from ART treatment. Further large cohort studies are warranted to determine an exact cutoff point for AMH to provide an accurate ART success prediction.

Protective roles of seminal plasma exosomes and microvesicles during human sperm cryopreservation.

RESEARCH QUESTION: Do seminal plasma microvesicles and exosomes, as two subtypes of extracellular vesicles, exert cryoprotective properties in sperm cryopreservation? DESIGN: Microvesicles and exosomes isolated from normozoospermic semen samples (n = 10) by serial ultracentrifugation were determined using scanning electron microscopy, dynamic light scattering and western blot analysis. The interactions between extracellular vesicles and spermatozoa were detected using Dil labelling. Purified spermatozoa from different normozoospermic samples (n = 25) were then treated individually with exosomes or microvesicles for 1 h and subsequently cryopreserved. The effects of extracellular vesicles during cryopreservation were investigated by determining post-thaw sperm motility, morphology, viability, reactive oxygen species (ROS) generation, lipid peroxidation, total antioxidant capacity (TAC), mitochondrial membrane potential (MMP), DNA integrity, and apoptosis rate. RESULTS: Microvesicles and exosomes displayed a round-shape morphology, with about 70% of exosomes ranging from 43-144 nm, microvesicles ranging from 144.5-486 nm and both expressed tetraspanin markers. Fluorescence microscopy showed that exosomes and microvesicles absorbed mainly in the sperm head and less frequently in the neck and tail. The post-thawing results indicated that the diluent with exosomes or microvesicles had improved sperm motility (P = 0.007), morphology (P < 0.001) and viability (P < 0.001) compared with untreated samples. The ROS levels decreased significantly (P = 0.001), with a consequent decrease in DNA damage (P = 0.001). The TAC activity (P = 0.001) and MMP levels (P = 0.001) were also significantly improved; levels of malondialdehyde (MDA) (P = 0.62) and apoptosis rate (P = 1.000) remained unchanged. CONCLUSION: Seminal plasma microvesicles and exosomes could protect spermatozoa from cryopreservation chilling injuries.

Serum progesterone levels greater than 32.5 ng/ml on the day of embryo transfer are associated with lower live birth rate after artificial endometrial preparation: a prospective study.

BACKGROUND: Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during frozen embryo transfer (FET) cycles. However, still the questions regarding the maximum threshold level, and the highest allowed dosage of hormonal medications remain unresolved. The present study was conducted to determine whether there is any relationship between the serum progesterone and estradiol levels on the day of ET, and live birth rate (LBR) in patients receiving HRT in FET cycles. METHODS: In this prospective cohort study, eligible women who were undergoing their first or second FET cycles with the top graded blastocyst stage embryos were included. All patients received the same HRT regimen. FET was scheduled 5 days after administration of the first dosage of progesterone. On the morning of ET, 4-6 h after the last dose of progesterone supplementation, the serum progesterone (P4, ng/ml) and estradiol (E2, pg/ml) levels were measured. RESULTS: Amongst the 258 eligible women that were evaluated, the overall LBR was 34.1 % (88/258). The serum P4 and E2 values were divided into four quartiles. The means of women's age and BMI were similar between the four quartiles groups. Regarding both P4 and E2 values, it was found that the LBR was significantly lower in the highest quartile group (Q4) compared with the others, (P = 0.002 and P = 0.042, respectively). The analysis of the multivariable logistic regression showed that the serum level of P4 on ET day, was the only significant predictive variable for LBR. The ROC curve revealed a significant predictive value of serum P4 levels on the day of ET for LBR, with an AUC = 0.61 (95 % CI: 0.54-0.68, P = 0.002). The optimum level of serum P4, with 70 % sensitivity and 50 %specificity for LBR, was 32.5 ng/ml. CONCLUSIONS: The present study suggests that a serum P4 value at the maximum threshold on the day of FET is associated with reduced LBR following blastocyst transfer. Therefore, measuring and monitoring of P4 levels during FET cycles might be necessary. However, the results regarding the necessity for the screening of serum E2 levels before ET, are still controversial, and further prospective studies are required.

Effect of sulforaphane on apoptosis, reactive oxygen species and lipids peroxidation of human sperm during cryopreservation.

Sperm cryopreservation is a common procedure to preserve viable sperm for an indefinite period. This procedure has numerous detrimental effects on sperm function due to increased generation of reactive oxygen species (ROS). During cryopreservation, while ROS increases, antioxidant enzymes level decreases. It has been shown that a relationship exist between lower antioxidant levels and infertility. l-Sulforaphane (SFN) is an isothiocyanate in cruciferous vegetables of the brassica class that has potent protective effects against oxidative stress. The purpose of the present study was to evaluate the effects of SFN supplementation during the freeze-thaw process on different parameters of human spermatozoa which can influence sperm fertilizing ability. Samples were collected from 25 healthy men and each sample was divided into three groups: fresh, control (untreated frozen/thawed samples) and treatment (treated frozen/thawed with SFN) groups. Sperm parameters, ROS production (using flow cytometry), plasma membrane integrity (using flow cytometry), Lipid peroxidation (using ELISA) were evaluated. Our results demonstrated that 5 µM SFN improved all parameters of sperm including viability (P < 0.001), motility, and morphology (P < 0.05) after the freeze-thaw process. Furthermore, SFN reduced the levels of intracellular hydrogen peroxide (P < 0.01) and superoxide anion (P < 0.05). Also, SFN significantly increased the percentage of viable sperm cells with the intact plasma membrane (P < 0.001) and decreased the level of lipid peroxidation after the freeze-thaw process (P < 0.01).Our findings showed that spermatozoa treatment with 5 µM SFN before the freeze-thaw process has protective effects against oxidative stress and could decrease the detrimental effects of this process on sperm quality.

Does myoinositol supplement improve sperm parameters and DNA integrity in patients with oligoasthenoteratozoospermia after the freezing-thawing process?

Sperm cryopreservation is a routine method in andrology and IVF laboratory. However, the sperm quality and its fertilizing capacity have been decreased during this process. The purpose of this experiment was to determine the role of myoinositol as a supplement in amelioration of total and progressive sperm motility, DNA fragmentation, total antioxidant capacity (TAC), reactive oxygen species (ROS), and lipid peroxidation after the freezing-thawing process on patients with oligoasthenoteratozoospermia (OAT) syndrome. Semen samples obtained from 40 patients were divided into two aliquots and freezed with simple and 2 mg/mL myoinositol (MYO) supplemented freezing media. All samples were thawed and assessed after one month. Semen parameters were analyzed in terms of the motility by CASA, the level of total ROS by fluorimetry, TAC and MDA by colorimetric assay and finally DNA fragmentation by TUNEL assay. Our results clearly showed that MYO could improve total (37.46 vs. 12.91, p < 0.001) and progressive motility (21.92 vs. 6.49, p < 0.001) in experimental group compared to control group. A higher TAC level was observed in the MYO treated group in comparison to control group (1.11 vs. 0.91, p = 0.05). While MYO supplementation could not be effective on ROS level, it reduced DNA fragmentation of sperm after freeze-thaw process (p = 0.01). Therefore, MYO could be a good supplement for sperm freezing to reduce the detrimental effects of freezing process especially on DNA integrity, which is an important factor in the success of ART, in OAT suffered patients.

A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer.

BACKGROUND: Prostate cancer is the second most common malignancy in men in the world, and radiotherapy is used as a standard treatment modality for this cancer. Although this treatment modality effectively kills prostate cancerous cells, it unavoidably irradiates the organs/tissues that are away from the treatment site. In this regard, radiation-induced testicular toxicities following prostate radiotherapy can affect sexual function, reproduction, and quality of life in cancer survivors. This review summarizes the available data on testicular exposure to radiation during prostate radiotherapy and the consequences on testicular function. METHODS: To illuminate the radiation-induced testicular toxicities following prostate radiotherapy, a systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline in PubMed, Web of Science, Scopus, Embase, and clinical trials electronic databases up to September 2018. According to a set of prespecified inclusion and exclusion criteria, 31 eligible articles providing data on testicular function following radiotherapy in patients with prostate cancer were included in the study. RESULTS: According to the different radiotherapeutic techniques used for prostate cancer treatment, the total tumor dose and scattered testicular dose values were ranging from 36.25 to 78.00 Gy and 0.06 to 6.48 Gy, respectively. Luteinizing hormone and follicle-stimulating hormone levels after prostate radiotherapy were significantly higher in comparison with the pretreatment levels. Around 60% of the studies showed that testosterone levels after prostate radiotherapy were significantly lower than the pretreatment levels. Furthermore, erectile dysfunction (ED), as an adverse side effect resulting from prostate radiotherapy, was reported and this complication is significantly correlated with lower satisfaction with sexual life. Testicular atrophy following prostate radiotherapy has also been observed and its frequency in patients with prior prostate radiotherapy is 2.5 times more than that in the patients without prior radiotherapy. CONCLUSION: The data revealed that the scattered dose to testicular tissues during prostate radiotherapy can lead to testicular atrophy, variation of the male sex hormones, and quality of sexual life.

Adjuvant chemotherapy with melatonin for targeting human cancers: A review.

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.

Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy.

Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.

Disruption of the redox balance with either oxidative or anti-oxidative overloading as a promising target for cancer therapy.

Oxidative stress acts as a double-edged sword by being both a promoter and a suppressor of cancer. Moderate oxidative stress is beneficial for cancer cell proliferative and invasiveness features, while overexposure of the cells to oxidative insults could induce cancer cell apoptosis and reduce hypoxia along with modulating the immune system for regression of tumor. Cancer cells and cancer stem cells have highly efficient redox systems that make them resistant to oxidative insults. The redox disruptive approach is an area of current research and key for oxidative targeted cancer therapies. This disruption is applicable by using either oxidative or anti-oxidative overloading strategies, specifically on cancer cells without influencing normal cells or tissues around tumor. The activity of tumor suppressor cells within tumor microenvironment is needed to be maintained in patients receiving such approaches.

Macrophage polarity in cancer: A review.

Macrophages are the most abundant cells within the tumor stroma displaying noticeable plasticity, which allows them to perform several functions within the tumor microenvironment. Tumor-associated macrophages commonly refer to an alternative M2 phenotype, exhibiting anti-inflammatory and pro-tumoral effects. M2 cells are highly versatile and multi-tasking cells that directly influence multiple steps in tumor development, including cancer cell survival, proliferation, stemness, and invasiveness along with angiogenesis and immunosuppression. M2 cells perform these functions through critical interactions with cells related to tumor progression, including Th2 cells, cancer-associated fibroblasts, cancer cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells. M2 cells also have negative cross-talks with tumor suppressor cells, including cytotoxic T cells and natural killer cells. Programed death-1 (PD-1) is one of the key receptors expressed in M2 cells that, upon interaction with its ligand PD-L1, plays cardinal roles for induction of immune evasion in cancer cells. In addition, M2 cells can neutralize the effects of the pro-inflammatory and anti-tumor M1 phenotype. Classically activated M1 cells express high levels of major histocompatibility complex molecules, and the cells are strong killers of cancer cells. Therefore, orchestrating M2 reprogramming toward an M1 phenotype would offer a promising approach for reversing the fate of tumor and promoting cancer regression. Macrophage switching toward an anti-inflammatory M1 phenotype could be used as an adjuvant with other approaches, including radiotherapy and immune checkpoint blockades, such as anti-PD-L1/PD-1 strategies.

Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients.

PURPOSE: AKTs have a pivotal role in the granulosa-lutein cell (GC) proliferation and folliculogenesis, and there is a reciprocal feedback between AKT with androgen. Therefore, we aimed to evaluate the role of AKTs in GCs of hyperandrogenic (+HA) PCOS cases. METHOD: There were three groups: control, +HA PCOS and -HA (non-hyperandrogenic) PCOS. All groups were subjected to GnRH antagonist protocol for stimulation of ovulation. Follicular fluid was aspirated from large follicles, and GCs were isolated using cell strainer method. AKT1, AKT2, AKT3, and androgen receptor (AR) mRNA expressions were analyzed with quantitative real-time PCR (qRT-PCR), and total-AKT and p-AKT (Ser473 & Thr308) were investigated using western blotting. RESULTS: There were high levels of AKT1, AKT2, and AR mRNA expressions and high levels of p-AKT protein expression in the +HA PCOS group (p ≤ 0.05). There was a direct positive correlation between free testosterone (FT) and total testosterone (TT) with the levels of AKT1, AKT2, and p-AKT (Ser473), and also between FT with the levels of AR. CONCLUSION: High expressions of AKT1 and AKT2 through possible relation with androgen may cause GCs dysfunction in the +HA PCOS patients.

Effect of Trolox on sperm quality in normozospermia and oligozospermia during cryopreservation.

This study evaluated the effects of different concentrations of Trolox supplementation to cryoprotective agent (CPA) on post-thaw apoptosis-like events that include translocation of phosphatidyl serine (PS) to the cell surface, alterations in mitochondrial membrane potential (MMP), and DNA integrity of normozoospermic and oligoozoospermic semen samples. Spermatozoa from 20 normozoospermic men and 20 patients with oligoozoospermia were cryopreserved with cryo-protective agent containing 0, 20, 40, and 80 µM Trolox. Pre-cryopreservation and post-thaw sperm MMP, PS externalization and DNA fragmentation were evaluated by flow cytometry. Sperm frozen in extender with Trolox had greater MMP, lower DNA fragmentation and externalization of PS in both groups, though the most effective dose of Trolox in normozoospermic and oligoozoospermic semen samples were different. These findings support the use of Trolox as freezing extender supplement to improve the quality of cryopreserved human sperm, measured in terms of early apoptosis changes and DNA integrity, in both normozoospermic and oligoozoospermic men.

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial.

BACKGROUND: This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS). METHODS: Fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial. RESULTS: Resveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05). CONCLUSIONS: These findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction. TRIAL REGISTRATION NUMBER: http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

Astaxanthin treatment ameliorates ER stress in polycystic ovary syndrome patients: a randomized clinical trial.

Astaxanthin (ASX), as a natural carotenoid compound, exists in various types of seafood and microorganisms. It has several possible beneficial therapeutic effects for patients with polycystic ovary syndrome (PCOS). Patients with PCOS also suffer from endoplasmic reticulum (ER) stress. In the present work, it was hypothesized that ER stress could be improved by ASX in PCOS patients. Granulosa cells (GCs) were obtained from 58 PCOS patients. The patients were classified into ASX treatment (receiving 12 mg/day for 60 days) and placebo groups. The expression levels of ER stress pathway genes and proteins were explored using Western blotting and quantitative polymerase chain reaction. To assess oxidative stress markers, follicular fluid (FF) was gained from all patients. The Student's t test was used to perform statistical analysis. After the intervention, ASX led to a considerable reduction in the expression levels of 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and X-box-binding protein 1 compared to the placebo group, though the reduction in the messenger RNA (mRNA) expression level of activating transcription factor 6 was not statistically significant. However, ASX significantly increased the ATF4 expression level. GRP78 and CHOP protein levels represented a considerable decrease in the treatment group after the intervention. In addition, a statistically significant increase was found in the FF level of total antioxidant capacity in the treatment group. Based on clinical outcomes, no significant differences were found between the groups in terms of the oocyte number, fertilization rate, and fertility rate, but the ASX group had higher rates of high-quality oocytes, high-quality embryo, and oocyte maturity compared to the placebo group. Our findings demonstrated that ER stress in the GCs of PCOS patients could be modulated by ASX by changing the expression of genes and proteins included in the unfolding protein response.Trial registration This study was retrospectively registered on the Iranian Registry of Clinical Trials website ( www.irct.ir ; IRCT-ID: IRCT20201029049183N, 2020-11-27).

The Effect of Astaxanthin on Motility, Viability, Reactive Oxygen Species, Apoptosis, and Lipid Peroxidation of Human Spermatozoa During the Freezing-Thawing Process.

Cryopreservation of spermatozoa is a general procedure to preserve viable sperm for an indefinite period. Despite the efficiency of sperm cryopreservation, excessive reactive oxygen species (ROS) production during cryopreservation can induce structural and functional changes in spermatozoa. Also, cryopreservation has been shown to decrease the spermatozoa's antioxidant activity inducing them to be more sensitive to damage caused by ROS. Experimental evidence suggests that astaxanthin (AXT) has essential activities such as antioxidant, antibacterial, and antithrombotic properties. Therefore, this study aimed to evaluate the effect of AXT on the sperm quality of healthy men during freezing-thawing. In the first phase, 10 semen samples with different concentrations of AXT (0.0, 0.5, 1, and 2 µM) were cryopreserved to achieve an optimal dose of AXT. Then, motility, viability, and phosphatidylserine (PS) externalization were evaluated. In the second phase, 25 samples were collected and divided into 3 groups: fresh group, control group (untreated frozen-thawed samples), and AXT group (treated frozen-thawed with AXT). Then, samples were cryopreserved in freezing media supplemented with or without the optimal concentration of AXT (1 µM). After thawing, the levels of sperm parameters, including motility (using a computer-assisted sperm analyzer), viability (eosin-nigrosin), early apoptotic change (annexin V/propidium iodide), ROS (flow cytometry), and lipid peroxidation (LPO) (using enzyme-linked immunosorbent assay), were evaluated. Our results showed that the addition of 1 µM AXT to sperm freezing media improved all parameters of sperm motility and viability (p ≤ 0.05). Furthermore, it could reduce the levels of ROS parameters (intracellular hydrogen peroxide and superoxide) compared with the control group (p ≤ 0.05). Also, AXT significantly decreased the level of PS externalization (p ≤ 0.05) and LPO (p ≤ 0.05) after the freezing-thawing process. In conclusion, our findings demonstrated that human semen treatment with 1 µM AXT before the freezing-thawing process has protective effects against oxidative stress and could diminish the destructive effects of this process on sperm quality.

Metabolic risk factors of ovarian cancer: a review.

Ovarian cancer continues to be the leading cause of death from gynecological cancers. Despite inconsistent results, patients with metabolic abnormalities, including obesity and diabetes mellitus (DM), have poorer outcomes, showing a correlation with ovarian cancer incidence and ovarian cancer survival. Since ovarian cancer is the most common cancer in women, and considering the increasing prevalence of obesity and DM, this paper reviews the literature regarding the relationship between the aforementioned metabolic derangements and ovarian cancer, with a focus on ovarian cancer incidence, mortality, and likely mechanisms behind them. Several systematic reviews and meta-analyses have shown that obesity is associated with a higher incidence and poorer survival in ovarian cancer. Although more studies are required to investigate the etiological relation of DM and ovarian cancer, sufficient biological evidence indicates poorer outcomes and shorter survival in DM women with ovarian cancer. A variety of pathologic factors may contribute to ovarian cancer risk, development, and survival, including altered adipokine expression, increased levels of circulating growth factors, altered levels of sex hormones, insulin resistance, hyperinsulinemia, and chronic inflammation. Thus, obesity and DM, as changeable risk factors, can be targeted for intervention to prevent ovarian cancer and improve its outcomes.

A randomized exploratory trial to assess the effects of resveratrol on VEGF and TNF-α 2 expression in endometriosis women.

Resveratrol, a naturally synthesized polyphenolic compound found in some fruits, has anti neoplastic, anti-inflammatory, anti-oxidative, and anti-angiogenic properties. Angiogenesis is an important process in endometriosis which provides blood supply for implantation, proliferation and survival of endometriotic lesions. In this study, we assessed the effects of resveratrol on vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) expression in the eutopic endometrium of infertile patients with endometriosis within the window of implantation as a randomized exploratory trial. Subjects, who confirmed their endometriosis (stage III-IV) by a pathologist after laparoscopic surgery, were recruited to the present trial. A total of 34 patients were randomly divided into treatment (n = 17) and control (n = 17) groups, beside the routine protocol for treatment of endometriosis, they received resveratrol and placebo (400 mg) for 12-14 weeks, respectively. Endometrial tissue was collected from both groups before and after the intervention in the mid-secretory phase. Gene and protein expression levels of VEGF and TNF-α in the eutopic endometrium were assessed by Real-Time PCR and Western blotting, respectively. VEGF and TNF-α gene and protein levels in the treatment group showed significant decrease following intervention. It seems resveratrol may improve the endometrium of endometriosis patients in window of implantation period by modifying the expression of VEGF and TNF-α but further investigations are needed to reveal the potential role of this compound.

Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.

Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1ß, TNF-α, TGF-ß, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators.

The effect of acupressure at the Sanyinjiao point (SP6) on primary dysmenorrhea in students resident in dormitories of Tabriz.

BACKGROUND: There are two types of primary dysmenorrhea (spasmodic and congestive) which differ from each other in terms of the occurrence time in menstrual cycle, pain quality and other symptoms. The present study aimed to determine the effect of acupressure at the Sanyinjiao point (SP-6) on severity of menstrual symptoms (primary outcome) and the duration of resting time as well as the number of ibuprofen consumption (secondary outcome) in the two types of primary dysmenorrhea. METHODS: This was a clustered randomized controlled trial on 72 eligible students residing in dormitories of public universities of Tabriz, Iran. Determining the type of primary dysmenorrhea using a Menstrual symptoms questionnaire (MSQ), 36 participants which suffered from each type of dysmenorrhea were enrolled from the four dormitories. The dormitories were randomly divided into intervention and control groups. No intervention was carried out at the first cycle. During the two next cycles, Sanyinjiao point of the subjects in the intervention group was pressed for twenty minutes at the time of pain. The subjects in both groups were allowed to consume ibuprofen, if needed. During these three cycles, the participants recorded and reported menstrual symptoms severity, duration of resting time and the number of the used ibuprofen. RESULTS: The severity of menstrual symptoms and duration of resting time in the 2(nd) and 3(rd) cycles were significantly reduced more than control groups for both spasmodic and congestive types of primary dysmenorrhea. In addition, the aver-age numbers of ibuprofen pills taken by both intervention groups was significantly less than the control groups. There was no significant difference between the two intervention groups in terms of any of the outcomes. CONCLUSIONS: Acupressure is effective on lowering the symptoms of dysmenorrhea and duration of resting time almost equally in both spasmodic and congestive types. Therefore, using this method either alone or along with other methods is recommended to treat dysmenorrhea.