Propolis Protects GC-1spg Spermatogonial Cells against Tert-Butyl Hydroperoxide-Induced Oxidative Damage.

Propolis is a natural resin produced by honeybees with plenty of pharmacologic properties, including antioxidant activity. Oxidative stress disrupts germ cell development and sperm function, with demonstrated harmful effects on male reproduction. Several natural antioxidants have been shown to reduce oxidative damage and increase sperm fertility potential; however, little is known about the effects of propolis. This work evaluated the role of propolis in protecting spermatogonial cells from oxidative damage. Propolis' phytochemical composition and antioxidant potential were determined, and mouse GC-1spg spermatogonial cells were treated with 0.1-500 µg/mL propolis (12-48 h) in the presence or absence of an oxidant stimulus (tert-butyl hydroperoxide, TBHP, 0.005-3.6 µg/mL, 12 h). Cytotoxicity was assessed by MTT assays and proliferation by Ki-67 immunocytochemistry. Apoptosis, reactive oxygen species (ROS), and antioxidant defenses were evaluated colorimetrically. Propolis presented high phenolic and flavonoid content and moderate antioxidant activity, increasing the viability of GC-1spg cells and counteracting TBHP's effects on viability and proliferation. Additionally, propolis reduced ROS levels in GC-1spg, regardless of the presence of TBHP. Propolis decreased caspase-3 and increased glutathione peroxidase activity in TBHP-treated GC-1spg cells. The present study shows the protective action of propolis against oxidative damage in spermatogonia, opening the possibility of exploiting its benefits to male fertility.

Anxiety and depression among nursing students during the COVID-19 lockdown: A cross-sectional correlational study.

AIMS AND OBJECTIVES: To determine the prevalence and levels of anxiety and depression symptoms among nursing students during the coronavirus lockdown, and to examine factors associated with higher levels of anxiety and depression on this population. BACKGROUND: Nursing students deal with diverse stressors during their university lives. Confinement measures during COVID-19 outbreak may have influenced students' mental health and well-being. Anxiety and depression are common among nursing students due to different factors. Evidence relating to anxiety and depression in nursing student population during SARS-CoV-2 pandemic is limited. DESIGN: A cross-sectional descriptive co-relational study during the lockdown due to the coronavirus outbreak in Spain was conducted. METHODS: An online questionnaire was developed by using google forms. Sociodemographic characteristics form, and the Spanish version of the Hospital Anxiety and Depression Scale (HADS) were used. Spanish nursing students across the country were enrolled. Data collection was performed between 4 April 2020 and 21 April 2020. A multivariate analysis was performed to determine the association between sociodemographic variables, COVID-19 and HADS scores. RESULTS: 1319 participants were enrolled. The sample was formed by 87.1% female students with a mean age of 22 years (SD ± 5.677). We found a mean score of 8.47 ± 4.104 on Scale HADS-Anxiety and 6.80 ± 2.988 on HADS-Depression. 31.6% students presented abnormal scores of anxiety symptoms, and only 11.4% participants revealed abnormal scores on HADS-Depression. CONCLUSIONS: The reported prevalence of anxiety and depression symptoms on nursing students during the COVID-19 lockdown is 56.4% and 38.2%, respectively. 43.6% of the sample scored normal anxiety levels, and 61.8% obtained normal depression levels. Higher anxiety and depression levels were statistically associated with being a first-year student, being a smoker, feeling fear, feeling stress and having any close family member infected. RELEVANCE TO CLINICAL PRACTICE: These data should be valuable for detection and for further treatment decision of this disorders at the initial stage and could be important to prevent further damages to mental health and promote physical, psychological and well-being among this population.

Ethical conflict among critical care nurses during the COVID-19 pandemic.

BACKGROUND: Ethical conflict is a problem with negative consequences, which can compromise the quality and ethical standards of the nursing profession and it is a source of stress for health care practitioners', especially for nurses. OBJECTIVES: The main aim of this study was to analyze Spanish critical care nurses' level of exposure to ethical conflict and its association with sociodemographic, occupational, and COVID-19-related variables. Research Design, Participants, and Research context: This was a quantitative cross-sectional descriptive study conducted among 117 nurses working in critical care units. Data collection tools were sociodemographic, occupational, and COVID-19-related questionnaires and previously validated Spanish version of Ethical Conflict in Nursing Questionnaire-Critical Care Version. ETHICAL CONSIDERATIONS: We obtained permission from the Ethics Committee and participants' informed consent. FINDINGS: Data indicates a moderate level of exposure to ethical conflicts. The most frequent ethical conflicts were related to situations about "treatment and clinical procedures." The most intensity of ethical conflicts was related to situations about "treatment and clinical procedures" and "dynamics of the service and working environment." No statistical significance was identified between the socio-demographic variables and level of exposure to ethical conflicts. However, for critical care nurses working in ICU, nurses with perceived worked stress had a higher level of exposure to ethical conflicts. Likewise, critical care nurses whose family/friends were infected with COVID-19 had a higher level of exposure. CONCLUSIONS: Critical care nurses experience a moderate level of exposure to ethical conflicts which is consistent with the results of previous studies. A deeper understanding of ethical conflicts in conflictive situations allows recognition of the situations that occur in everyday clinical practice, identification of the ethical conflicts, and facilitation of the nurses working in the challenging clinical situation.

Effects of the endocrine disruptor vinclozolin in male reproduction: a systematic review and meta-analysis†.

Endocrine-disrupting chemicals have become an issue of scientific and public discussion. Vinclozolin (VNZ) is a fungicide that competitively antagonizes the binding of natural androgens to their receptor, disturbing the function of tissues that are sensitive to these hormones, as is the case of the male reproductive organs. A systematic review with meta-analyses of rodent studies was conducted to answer the following question: Does exposure to VNZ affect sperm parameters and testicular/epididymal weight? The methodology was prespecified according to the Cochrane Handbook for Systematic Reviews and PRISMA recommendations. Sixteen articles met the inclusion criteria, comprising a total of 1189 animals. The risk of publication bias was assessed using the Trim and Fill adjustment, funnel plot, and Egger regression test. Heterogeneity and inconsistency across the findings were tested using the Q-statistic and I2 of Higgins, respectively. Sensitivity was also analyzed. Statistical analysis was performed on Comprehensive Meta-Analysis software (Version 2.0), using random models and weighted mean differences along with a 95% confidence interval. Sperm motility, counts, daily sperm production (evidence of publication bias), and epididymis weight were decreased in VNZ-treated animals. Exposure length and dose, as well as the time point of exposure, influenced the obtained results. Despite the moderate/high heterogeneity observed, the sensitivity analysis overall demonstrated the robustness of the findings. The quality scores of the included studies were superior to 4 in a total of 9, then classified as good. The obtained data corroborate the capability of VNZ exposure to disrupt spermatogenic output and compromise male fertility.

Necrotizing infundibulo-hypophysitis: case-report and literature review.

PURPOSE: We describe a rare case of histopathologic-proven necrotizing infundibulo-hypophysitis (NIH). CLINICAL HISTORY: A 40-year-old female presented with coexistence of central diabetes insipidus and hypopituitarism. Imaging disclosed a thickened infundibulum and a diffusely enlarged pituitary mass with gadolinium rim enhancement pattern. Microsurgical endonasal transsphenoidal resection was performed. The presence of extensive liquefactive necrosis, surrounded by lymphoplasmocytic inflammatory infiltrate, allowed for the diagnosis of NIH. Follow-up cranial imaging 10 months after surgery showed no evidence of reappearance of the lesion. There was no progression to panhypopituitarism. CONCLUSION: Surgery and histopathological confirmation are the key diagnostic feature in NIH. The current case is the fifth report of NIH and the first one with an indolent course and without progression to panhypopituitarism so far.

Sweet Cherries as Anti-Cancer Agents: From Bioactive Compounds to Function.

Sweet cherries (Prunus avium L.) are among the most appreciated fruits worldwide because of their organoleptic properties and nutritional value. The accurate phytochemical composition and nutritional value of sweet cherries depends on the climatic region, cultivar, and bioaccessibility and bioavailability of specific compounds. Nevertheless, sweet cherry extracts are highly enriched in several phenolic compounds with relevant bioactivity. Over the years, technological advances in chemical analysis and fields as varied as proteomics, genomics and bioinformatics, have allowed the detailed characterization of the sweet cherry bioactive phytonutrients and their biological function. In this context, the effect of sweet cherries on suppressing important events in the carcinogenic process, such as oxidative stress and inflammation, was widely documented. Interestingly, results from our research group and others have widened the action of sweet cherries to many hallmarks of cancer, namely metabolic reprogramming. The present review discusses the anticarcinogenic potential of sweet cherries by addressing their phytochemical composition, the bioaccessibility and bioavailability of specific bioactive compounds, and the existing knowledge concerning the effects against oxidative stress, chronic inflammation, deregulated cell proliferation and apoptosis, invasion and metastization, and metabolic alterations. Globally, this review highlights the prospective use of sweet cherries as a dietary supplement or in cancer treatment.

Spanish oncology nurses: Assessment and relationship between resilience and emotional labour status.

OBJECTIVE: To investigate nurses' resilience and emotional labour (EL) status in the oncology context as well as to examine the relationship between resilience and EL status. METHODS: Cross-sectional, correlational quantitative design. The selected setting is the oncology centre at a referral and teaching hospital in northern Spain. One hundred and two oncology nurses were included. Socio-demographic data were obtained from a questionnaire. Data for resilience and EL status were drawn from validated Spanish questionnaires. RESULTS: Oncology nurses reported a moderate to high level of resilience and experienced less intense EL. Professional rank was the only factor identified that influenced resilience (p < .05). Gender, educational level, shift work, work department, and oncology work experience were statistically significant when correlated with the EL of oncology nurses (p < .05). There was a positive correlation between resilience and two EL factors (p < .05). CONCLUSIONS: The information gained from this study may raise awareness of the importance of resilience and EL in the nursing profession. It would be important to develop a programme of resilience training and emotional regulation and integrate these programmes into educational systems in order to help enhance nursing students' and clinical nurses' resilience and emotional competency.

In vitro evaluation of potential benefits of a silica-rich thermal water (Monfortinho Thermal Water) in hyperkeratotic skin conditions.

Thermal therapy has gained popularity over the years, and Portugal is one of the richest European countries in mineral therapeutic waters. The interest in the use of these natural mineral waters (NMW) for dermatologic purposes is continuously growing but there is a lack of scientific studies supporting its health benefits. The study aims to investigate the effect of a silica-rich NMW in skin cell homeostasis using two representative cell lines of the epidermis and dermis, keratinocytes and fibroblasts, respectively, in addition to a macrophage cell line. Mouse skin fibroblasts, macrophages and human keratinocytes were exposed to culture medium prepared with NMW. Cell metabolism (MTT or resazurin assays) and cell proliferation (trypan blue exclusion dye assay) were investigated. Migration (scratch-wound assay) and senescence (ß-galactosidase activity assay) of fibroblasts were also studied. Exposure to NMW compromised the cell metabolic state of all the cell lines tested. This impairment was more pronounced in skin keratinocytes (60% reduction) relatively to skin fibroblasts (45% reduction) or macrophages (25% reduction). Proliferation of macrophages was reduced threefold upon exposure to thermal water, compared to controls. No differences were observed in migration between fibroblasts exposed to NMW and controls, while a potentiation of senescence of these cells was observed. Our results shed light in the bioactive effects of a silica-rich NMW supporting its therapeutic use. A reduction in both cell metabolism and proliferation of keratinocytes and macrophages supports the empirical clinical benefits of this NMW in hyperkeratotic conditions, such as psoriasis and atopic dermatitis.

Chemical signature and antimicrobial activity of Central Portuguese Natural Mineral Waters against selected skin pathogens.

The common therapeutic indications of Portuguese Natural Mineral Waters (NMWs) are primarily for respiratory, rheumatic and musculoskeletal systems. However, these NMWs have been increasingly sought for dermatologic purposes. Opposing to what is observed in the major European Thermal Centres, there are few scientific evidences supporting the use of Portuguese NMWs for clinical applications. The aim of this study was to characterize the antimicrobial profile of individual NMWs from the central region of Portugal and correlate the results with their physicochemical characterization. An extensive multivariate analysis (principal component analysis) was also performed to further investigate this possible correlation. Six collection strains representing skin microbiota, namely Staphylococcus aureus, Escherichia coli, Corynebacterium amycolatum, Candida albicans, Staphylococcus epidermidis and Cutibacterium acnes, were analysed, and their antimicrobial profile was determined using Clinical and Laboratory Standards Institute M07-A10, M45-A2, M11-A6 and M27-A3 microdilution methods. Different NMWs presented different antimicrobial profiles against the strains used; the physicochemical composition of NMWs seemed to be correlated with the different susceptibility profiles. Cutibacterium acnes showed a particularly high susceptibility to all NMWs belonging sulphurous/bicarbonated/sodic ionic profile, exhibiting microbial reductions up to 65%. However, due to the complex physicochemical composition of each water an overall conclusion regarding the effect of a specific ion on the growth of different microorganisms is yet to be known.

Presenteeism in nurses: comparative study of Spanish, Portuguese and Brazilian nurses.

AIM: To compare presenteeism levels among three samples of nurses and to identify the relationship between presenteeism and sociodemographic and professional characteristics. BACKGROUND: Presenteeism (going to work ill) is a phenomenon studied from different perspectives, and it has become especially important during the current COVID-19 outbreak; its connection to high healthcare costs, patient safety breaches and negative nurse well-being has been proved. INTRODUCTION: The nursing profession is particularly associated with caring for the culture of teamwork, loyalty to colleagues and professional identity. This condition enhances the 'super nurse phenomenon', even though nurses do not feel physically and psychologically able to work. METHODS: A multicentre, cross-sectional study was conducted in three different country contexts: Oviedo (Spain), Porto (Portugal) and São Paulo (Brazil). Nurses performing functions in hospitals and primary health care were enrolled. Informed consent and data collection questionnaires were hand delivered. The Stanford Presenteeism Scale-6 was applied. RESULTS: A total of 659 nurses participated. Portuguese nurses showed greater prevalence of presenteeism, followed by Brazilian and Spanish nurses. Younger nurses with less professional experience presented lower levels of presenteeism but greater psychological commitment. Male participants showed lower capacity to complete work when ill than female participants. CONCLUSIONS: Age and length of professional experience proved to be significant predictors of total presenteeism, although only professional experience revealed statistical significance in the adjusted model. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The knowledge of this phenomenon among nurses highlights the need for the development of strategies in the curriculum of nursing students and organizations. Resilience and ergonomic training should be applied in the training programmes of the students and reinforced by the health centre managers. It is essential that healthcare systems design worksite wellness programmes that pursue greater physical and mental well-being for healthcare professionals.

Regucalcin counteracts tert-butyl hydroperoxide and cadmium-induced oxidative stress in rat testis.

Regucalcin (RGN) is a calcium (Ca2+ )-binding protein with multiple physiological roles and has also been linked to the suppression of oxidative stress. It is widely known that oxidative stress adversely affects spermatogenesis, disrupting the development of germ cells, and interfering with sperm function. The present study aims to analyze the role of RGN modulating testicular oxidative stress. To address this issue, seminiferous tubules (SeT) from transgenic rats overexpressing RGN (Tg-RGN) and wild-type (WT) were cultured ex vivo for 24 h in the presence/absence of pro-oxidant stimuli, tert-butyl hydroperoxide (TBHP, 250 and 500 µM) and cadmium chloride (Cd, 10 and 20 µM). Noteworthy, SeT from Tg-RGN animals displayed a significantly higher antioxidant capacity and diminished levels of thiobarbituric acid reactive substances relatively to their WT counterparts, both in control and experimental conditions. Regarding the antioxidant defense systems, a significant increase in the activity of glutathione-S-transferase was found in the SeT of Tg-RGN whereas no differences were observed in superoxide dismutase activity throughout experimental conditions. The activity of apoptosis executioner caspase-3 was significantly increased in the SeT of WT rats treated with 250 µM of TBHP or 10 µM of Cd, an effect not seen in Tg-RGN animals. These results showed that the SeT of Tg-RGN animals displayed lower levels of oxidative stress and increased antioxidant defenses, exhibiting protection against oxidative damage and apoptosis. Moreover, the present findings support the antioxidant role of RGN in spermatogenesis, which may be an important issue of further research in the context of male infertility. Copyright © 2016 John Wiley & Sons, Ltd.

Metabolic Profiling and Classification of Propolis Samples from Southern Brazil: An NMR-Based Platform Coupled with Machine Learning.

The chemical composition of propolis is affected by environmental factors and harvest season, making it difficult to standardize its extracts for medicinal usage. By detecting a typical chemical profile associated with propolis from a specific production region or season, certain types of propolis may be used to obtain a specific pharmacological activity. In this study, propolis from three agroecological regions (plain, plateau, and highlands) from southern Brazil, collected over the four seasons of 2010, were investigated through a novel NMR-based metabolomics data analysis workflow. Chemometrics and machine learning algorithms (PLS-DA and RF), including methods to estimate variable importance in classification, were used in this study. The machine learning and feature selection methods permitted construction of models for propolis sample classification with high accuracy (>75%, reaching ∼90% in the best case), better discriminating samples regarding their collection seasons comparatively to the harvest regions. PLS-DA and RF allowed the identification of biomarkers for sample discrimination, expanding the set of discriminating features and adding relevant information for the identification of the class-determining metabolites. The NMR-based metabolomics analytical platform, coupled to bioinformatic tools, allowed characterization and classification of Brazilian propolis samples regarding the metabolite signature of important compounds, i.e., chemical fingerprint, harvest seasons, and production regions.

Paradoxical and contradictory effects of imatinib in two cell line models of hormone-refractory prostate cancer.

BACKGROUND: Imatinib mesylate is a chemotherapeutic drug that inhibits the tyrosine kinase activity of c-KIT and has been successfully used to treat leukemias and some solid tumors. However, its application for treatment of hormone-refractory prostate cancer (HRPC) has shown modest effectiveness and did not follow the outcomes in cultured cells or animal models. Moreover, the molecular pathways by which imatinib induces cytotoxicity in prostate cancer cells are poorly characterized. METHODS: Two cell line models of HRPC (DU145 and PC3) were exposed to 20 µM of imatinib for 6-72 hr. MTS assay was used to assess cell viability during the course of experiment. Gene expression analysis of c-KIT, cell-cycle and apoptosis regulators, and angiogenic factors was determined by means of real-time PCR, western blot, and/or immunocytochemistry. The enzymatic activity of the apoptosis effector, caspase-3, was determined by a colorimetric assay. RESULTS: Imatinib significantly decreased the viability of DU145 cells but paradoxically augmented the viability of PC3 cells. DU145 cells displayed diminished expression of anti-apoptotic Bcl-2 protein and augmented levels of caspase-8 and -9, as well as, increased enzymatic activity of caspase-3 in response to imatinib. No differences existed on the expression levels of apoptosis-related proteins in PC3 cells treated with imatinib, though the activity of caspase-3 was decreased. The mRNA levels of angiogenic factor VEGF were decreased in DU145-treated cells, whereas an opposite effect was seen in PC3. In addition, it was shown that DU145 and PC3 cells present a differential expression of c-KIT protein variants. CONCLUSION: DU145 and PC3 cells displayed a contradictory behavior in response to imatinib, which was underpinned by a distinct expression pattern (or activity) of target regulators of cell-cycle, apoptosis, and angiogenesis. The paradoxical effect of imatinib in PC3 cells may be related with the differential expression of c-KIT protein variants. Moreover, the present findings helped to understand the discrepancies in the efficacy of imatinib as therapeutic option in HRPC.

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

In the mammalian testis, spermatogenesis is a highly coordinated process of germ cell development, which ends with the release of 'mature' spermatozoa. The fine regulation of spermatogenesis is strictly dependent on sex steroid hormones, which orchestrate the cellular and molecular events underlying normal development of germ cells. Sex steroids actions also rely on the control of germ cell survival, and the programmed cell death by apoptosis has been indicated as a critical process in regulating the size and quality of the germ line. Recently, oestrogens have emerged as important regulators of germ cell fate. However, the beneficial or detrimental effects of oestrogens in spermatogenesis are controversial, with independent reports arguing for their role as cell survival factors or as apoptosis-inducers. The dual behaviour of oestrogens, shifting from 'angels to devils' is supported by the clinical findings of increased oestrogens levels in serum and intratesticular milieu of idiopathic infertile men. This review aims to discuss the available information concerning the role of oestrogens in the control of germ cell death and summarises the signalling mechanisms driven oestrogen-induced apoptosis. The present data represent a valuable basis for the clinical management of hyperoestrogenism-related infertility and provide a rationale for the use of oestrogen-target therapies in male infertility.

The diverse roles of calcium-binding protein regucalcin in cell biology: from tissue expression and signalling to disease.

Regucalcin (RGN) is a calcium (Ca(2+))-binding protein widely expressed in vertebrate and invertebrate species, which is also known as senescence marker protein 30, due to its molecular weight (33 kDa) and a characteristically diminished expression with the aging process. RGN regulates intracellular Ca(2+) homeostasis and the activity of several proteins involved in intracellular signalling pathways, namely, kinases, phosphatases, phosphodiesterase, nitric oxide synthase and proteases, which highlights its importance in cell biology. In addition, RGN has cytoprotective effects reducing intracellular levels of oxidative stress, also playing a role in the control of cell survival and apoptosis. Multiple factors have been identified regulating the cell levels of RGN transcripts and protein, and an altered expression pattern of this interesting protein has been found in cases of reproductive disorders, neurodegenerative diseases and cancer. Moreover, RGN is a serum-secreted protein, and its levels have been correlated with the stage of disease, which strongly suggests the usefulness of this protein as a potential biomarker for monitoring disease onset and progression. The present review aims to discuss the available information concerning RGN expression and function in distinct cell types and tissues, integrating cellular and molecular mechanisms in the context of normal and pathological conditions. Insight into the cellular actions of RGN will be a key step towards deepening the knowledge of the biology of several human diseases.

Face-to-face Information and Emotional Support from Trained Nurses Reduce Pain During Screening Mammography: Results from a Randomized Controlled Trial.

Pain and discomfort during breast examination can affect a woman's adherence to breast cancer-screening programs. The aim of this study was to determine whether a nursing intervention protocol that provides verbal information and support to women could reduce pain during mammography. A randomized controlled trial of 436 Spanish women aged 50-69 who attended a breast-screening program was performed. The experimental group received a customized nursing intervention that provided face-to-face information and emotional support during the examination. Pain and anxiety were measured using a visual analogue scale and the State-Trait Anxiety Inventory, respectively. Data regarding several potential confounders were also collected. The adjusted means of pain level in the study group were obtained from multiple linear regressions, and the adjusted odds ratios (OR) and 95% confidence intervals (CI) were obtained via logistic regression. After the intervention, the level of pain was significantly lower (p = .03) in the experimental group (0.98 ± 2.28) compared with the group treated with normal care (1.48 ± 2.29). Consequently, the probability of feeling pain during mammography was lower among women in the experimental group (OR = 0.44; 95% CI: 0.24-0.81). The intervention was more effective among women with the highest anxiety levels (OR = 0.33; 95% CI: 0.11-0.98), who did not expect pain (OR = 0.28; 95% CI: 0.08-0.97), and who did not fear the outcome of the mammography (OR = 0.18; 95% CI: 0.04-0.85). Providing verbal information, as well as supporting the women during the test, is a simple and achievable intervention for nurses and can help to reduce pain during screening mammography.

Regucalcin is an androgen-target gene in the rat prostate modulating cell-cycle and apoptotic pathways.

BACKGROUND: Regucalcin (RGN) is a calcium (Ca(2+) )-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated. METHODS: Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein. RESULTS: In vivo stimulation with 5α-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg-RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN. CONCLUSIONS: Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology.

The SCF/c-KIT system in the male: Survival strategies in fertility and cancer.

Maintaining the delicate balance between cell survival and death is of the utmost importance for the proper development of germ cells and subsequent fertility. On the other hand, the fine regulation of tissue homeostasis by mechanisms that control cell fate is a factor that can prevent carcinogenesis. c-KIT is a type III receptor tyrosine kinase activated by its ligand, stem cell factor (SCF). c-KIT signaling plays a crucial role in cell fate decisions, specifically controlling cell proliferation, differentiation, survival, and apoptosis. Indeed, deregulating the SCF/c-KIT system by attenuation or overactivation of its signaling strength is linked to male infertility and cancer, and rebalancing its activity via c-KIT inhibitors has proven beneficial in treating human tumors that contain gain-of-function mutations or overexpress c-KIT. This review addresses the roles of SCF and c-KIT in the male reproductive tract, and discusses the potential application of c-KIT target therapies in disorders of the reproductive system.

Expression pattern of G protein-coupled receptor 30 in human seminiferous tubular cells.

The role of estrogens in male reproductive physiology has been intensively studied over the last few years. Yet, the involvement of their specific receptors has long been a matter of debate. The selective testicular expression of the classic nuclear estrogen receptors (ERα and ERß) argues in favor of ER-specific functions in the spermatogenic event. Recently, the existence of a G protein-coupled estrogen receptor (GPR30) mediating non-genomic effects of estrogens has also been described. However, little is known about the specific testicular expression pattern of GPR30, as well as on its participation in the control of male reproductive function. Herein, by means of immunohistochemical and molecular biology techniques (RT-PCR and Western blot), we aimed to present the first exhaustive evaluation of GPR30 expression in non-neoplastic human testicular cells. Indeed, we were able to demonstrate that GPR30 was expressed in human testicular tissue and that the staining pattern was consistent with its cytoplasmic localization. Additionally, by using cultured human Sertoli cells (SCs) and isolated haploid and diploid germ cells fractions, we confirmed that GPR30 is expressed in SCs and diploid germ cells but not in haploid germ cells. This specific expression pattern suggests a role for GPR30 in spermatogenesis.