Polystyrene nanoplastics induce apoptosis, autophagy, and steroidogenesis disruption in granulosa cells to reduce oocyte quality and fertility by inhibiting the PI3K/AKT pathway in female mice.

BACKGROUND: Nanoplastics (NPs) are emerging pollutants that pose risks to living organisms. Recent findings have unveiled the reproductive harm caused by polystyrene nanoparticles (PS-NPs) in female animals, yet the intricate mechanism remains incompletely understood. Under this research, we investigated whether sustained exposure to PS-NPs at certain concentrations in vivo can enter oocytes through the zona pellucida or through other routes that affect female reproduction. RESULTS: We show that PS-NPs disrupted ovarian functions and decreased oocyte quality, which may be a contributing factor to lower female fertility in mice. RNA sequencing of mouse ovaries illustrated that the PI3K-AKT signaling pathway emerged as the predominant environmental information processing pathway responding to PS-NPs. Western blotting results of ovaries in vivo and cells in vitro showed that PS-NPs deactivated PI3K-AKT signaling pathway by down-regulating the expression of PI3K and reducing AKT phosphorylation at the protein level, PI3K-AKT signaling pathway which was accompanied by the activation of autophagy and apoptosis and the disruption of steroidogenesis in granulosa cells. Since PS-NPs penetrate granulosa cells but not oocytes, we examined whether PS-NPs indirectly affect oocyte quality through granulosa cells using a granulosa cell-oocyte coculture system. Preincubation of granulosa cells with PS-NPs causes granulosa cell dysfunction, resulting in a decrease in the quality of the cocultured oocytes that can be reversed by the addition of 17ß-estradiol. CONCLUSIONS: This study provides findings on how PS-NPs impact ovarian function and include transcriptome sequencing analysis of ovarian tissue. The study demonstrates that PS-NPs impair oocyte quality by altering the functioning of ovarian granulosa cells. Therefore, it is necessary to focus on the research on the effects of PS-NPs on female reproduction and the related methods that may mitigate their toxicity.

Exposure to polystyrene nanoplastics induces hepatotoxicity involving NRF2-NLRP3 signaling pathway in mice.

Nanoplastic contamination has been of intense concern by virtue of the potential threat to human and ecosystem health. Animal experiments have indicated that exposure to nanoplastics (NPs) can deposit in the liver and contribute to hepatic injury. To explore the mechanisms of hepatotoxicity induced by polystyrene-NPs (PS-NPs), mice and AML-12 hepatocytes were exposed to different dosages of 20 nm PS-NPs in this study. The results illustrated that in vitro and in vivo exposure to PS-NPs triggered excessive production of reactive oxygen species and repressed nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway and its downstream antioxidase expression, thus leading to hepatic oxidative stress. Moreover, PS-NPs elevated the levels of NLRP3, IL-1ß and caspase-1 expression, along with an activation of NF-κB, suggesting that PS-NPs induced hepatocellular inflammatory injury. Nevertheless, the activaton of NRF2 signaling by tert-butylhydroquinone mitigated PS-NPs-caused oxidative stress and inflammation, and inbihited NLRP3 and caspase-1 expression. Conversely, the rescuing effect of NRF2 signal activation was dramatically supressed by treatment with NRF2 inhibitor brusatol. In summary, our results demonstrated that NRF2-NLRP3 pathway is involved in PS-NPs-aroused hepatotoxicity, and the activation of NRF2 signaling can protect against PS-NPs-evoked liver injury. These results provide novel insights into the hepatotoxicity elicited by NPs exposure.

The emerging role of lysine succinylation in ovarian aging.

BACKGROUND: Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc. METHODS: The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level. RESULTS: Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc. CONCLUSION: The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.

Maternal exposure to a glyphosate-based herbicide impairs placental development through endoplasmic reticulum stress in mice.

Glyphosate-based herbicides (GBHs) are the most widely used agrochemicals worldwide, increasing the risk of their occurrence in the environment. This study aimed to explore effects and mechanisms of GBH exposure on placental development in vivo during pregnancy in mice. Pregnant mice received GBH by gavage at 0, 5, and 50 mg⋅kg-1⋅day-1 doses from gestational day (GD) 1 to GD 13 and were sacrificed on GD 13 or GD19. Our data indicated that GBH administration significantly increased the number of resorbed fetuses, reduced the weight of fetuses and placentas, and inhibited placental growth, as evident from decreased placental total area and spongiotrophoblast area on GD 19. GBH treatment also inhibited proliferation and induced apoptosis of placenta via upregulation of Bax, cleaved caspase-3 and -12 expression, and downregulation of B cell lymphoma (Bcl)-2 expression. Further study showed that GBH exposure significantly increased expression levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) mRNAs and proteins and triggered oxidative stress in placenta on GD 13 and GD 19. In conclusion, our findings suggest that maternal exposure to GBH can impair placental development through the endoplasmic reticulum stress-mediated activation of GRP78/PERK/CHOP signaling pathway in mice.

Multiscale characterization of seawater pipe erosion of B10 copper-nickel alloy welded joints.

In seawater pipeline, the welding joint is a non-uniform structure composed of welding seam, base metal and heat affected zone. It has inhomogeneity in chemical composition, organizational structure, residual stress, etc. As local defects and high turbulence accelerate corrosion, the welding joint is often the weakest link in pipeline corrosion. Herein, the electrochemical corrosion behavior of B10 alloy welded joint in flowing seawater is studied from macroscopic and submicroscopic viewpoints using AC impedance, linear polarization, array electrode and morphological characterization. The results reveal that the corrosion rate of weld metal (WM), base metal (BM) and heat-affected zone (HAZ) decreased with the increase of time. Combined with SEM and EDS analysis, it can be seen that the increase in time led to the decomposition and accumulation of corrosion products, which gradually enhanced the corrosion resistance of welded joints. At the submicroscopic scale, WM acts as a cathode to mitigate corrosion during the later stages of high flow rate.

Corrosion behavior of X80 pipeline steel local defect pits under static liquid film.

In this work, the corrosion electrochemical information under different thicknesses of liquid film was tested. The local corrosion development process of X80 steel under different thicknesses of liquid film was studied by combining the detection and analysis of scale and the matrix corrosion morphology. The corrosion was studied by EIS. The composition and microstructures of corrosion scale at different locations were detected by EDS and SEM, and the metal matrix was detected by 3D topography technology to analyze the local corrosion. The results show that a liquid film with a thickness greater than or equal to 1 mm has no effect on the mechanism of the corrosion process, but has a control effect on the corrosion rate and the time of each stage in corrosion. The corrosion process can be divided into two stages: in the early stage, the concentration of ions inside and outside ADP is the same, so the corrosion is uniform; in the later stage, due to the influence of CO2 dissolution and mass transfer distance, the cathodic reaction is mainly outside ADP and the anodic reaction is mainly inside ADP. In addition, corrosion acidification occurs in ADP, which enhances the corrosion process in ADP.

Effect of emerging pollutant fluoxetine on the excess sludge anaerobic digestion.

Fluoxetine (FLX), an emerging pollutant, has been detected in the sewage and excess sludge (ES) at substantial levels. So far, however, the impacts of FLX on the ES anaerobic digestion and the related mechanisms have never been investigated. In this work, the effects of FLX on the ES anaerobic digestion were explored by the batch test under moderate temperature condition. The results indicated the effect of FLX on ES digestion was dose-dependent. When FLX was at a low dose (0.1 mg/kg), FLX had no significant impact on the methane generation from the ES digestion. However，when FLX was 2.0 mg/kg, the cumulative methane production was only 91.2 ± 4.3 mL/g volatile suspended solids (VSS), which was about 59.9 ± 3.4% of the blank (without FLX). Mechanisms revealed that the presence of FLX has inhibited hydrolysis, acidification and methanogenesis. Enzyme activity analysis showed that FLX inhibited the activities of key enzymes in the process of hydrolysis, acidification and methanogenesis. The results of this work are of great significance to explain the role of FLX in the process of ES fermentation, and provide some reference for the subsequent utilization of ES.

Enhanced hydrogen production from food waste dark fermentation by potassium ferrate pretreatment.

Hydrogen generation from food waste anaerobic dark fermentation is identified as a promising strategy for resource recovery. In this work, an innovative strategy of using potassium ferrate (PF), a strong oxidant, to promote anaerobic dark fermentation of food waste to produce hydrogen has been reported. The experimental results revealed that PF enhanced the hydrogen production from food waste, the maximal hydrogen yield was 173.5 mL/g, and the optimal PF dosage was 0.4 g/g total suspended solids. PF shortened the lag phase for hydrogen generation from 120 to 96 h. Mechanisms investigation revealed that PF accelerated the disintegration of organic compounds and increased the soluble organic matter in the liquid phase. The strong oxidation of PF inhibited the processes of hydrolysis, acidification, acetogenesis, homoacetogenesis, and methanogenesis by using synthetic wastewater in the fermentation process. The inhibition of PF on these processes was further verified by the enzyme activity analysis. Economic analysis indicated that 0.1 g/g PF was the optimal dosage. PF treatment is a promising strategy to enhance the production of hydrogen from food waste dark fermentation.

PFOA evokes extracellular Ca2+ influx and compromises progesterone-induced response in human sperm.

Perfluorooctane acid (PFOA), a persistent organic pollutant, is ubiquitously present in the environment and may detrimentally affect male reproductive health. In this study, mature human sperm were in vitro exposed to different concentrations of PFOA (0.25, 2.5 or 25 µg/ml) alone or in combination with progesterone (P4) to evaluate the toxicity and the potential mechanism of action. Exposure to high-dose PFOA (25 µg/ml) alone for 4 h caused a decline in capacity of human spermatozoa to penetrate synthetic mucus, with an increased production of reactive oxygen species (ROS). Furthermore, PFOA treatment (2.5 and 25 µg/ml) evoked a transient rise in intracellular calcium concentration [Ca2+]i by activating the sperm-specific CatSper channel. However, preincubation with PFOA (2.5-25 µg/ml) for 4 h significantly suppressed P4-stimulated extracellular Ca2+ influx in human spermatozoa. Moreover, PFOA pretreatment at all concentrations evaluated markedly compromised P4-induced acrosome reaction and sperm penetration into viscous medium. Taken together, these results suggest that PFOA exposure may impair human sperm function through inducing oxidative stress and disturbing P4-induced Ca2+ signaling.

Exposure to acrylamide inhibits uterine decidualization via suppression of cyclin D3/p21 and apoptosis in mice.

Acrylamide (ACR), a neurotoxicity and carcinogenic chemical, has attracted considerable attention since it is present at high concentrations in thermally cooked carbohydrate-rich foods. ACR exposure significantly increased rate of fetal resorption, and decreased fetal body weights in mice. However, no detailed information is available about the effect of ACR on uterine decidualization, which is a vital process in the establishment of successful pregnancy. Thus, our aim of this study was to explore the effect and mechanism of ACR on uterine decidualization in vivo during mice pregnancy. Mice were gavaged with 0, 10, and 50 mg ACR /kg/day from gestational days (GD) 1 until GD 8, whereas pseudopregnant mice from pseudopregnant day (PPD) 4 until PPD 8. Results indicated ACR treatment dramatically reduced numbers of implanted embryos, and decreased the weights of implantation site and oil-induced uterus. Nevertheless, no significant difference was observed in the weights of no oil-induced uterus between control and ACR-treated group. Furthermore, ACR significantly reduced numbers of polyploidy and PCNA-positive decidual cells and expression of cyclin D3 and p21 proteins, and induced apoptosis of decidua, as presented by up-regulation of Bax and cleaved-caspase-3, and decreased Bcl-2 protein during normal pregnant and pseudopregnant process. In summary, ACR exposure significantly inhibited uterine endometrial decidualization via the apoptosis and suppression of cyclin D3/p21 in mice.

Attenuation of Perfluorooctane Sulfonate-Induced Steatohepatitis by Grape Seed Proanthocyanidin Extract in Mice.

Perfluorooctane sulfonate (PFOS), an environmentally persistent pollutant, has been revealed to elicit hepatic toxicity. In the current study, we investigated the protective role of grape seed proanthocyanidin extract (GSPE) against PFOS-caused steatohepatitis in mice. Animals were exposed intragastrically to PFOS (10 mg/kg/day), GSPE (150 mg/kg/day), or their combination. After 21 days of treatment, mice exposed to PFOS exhibited steatosis, oxidative stress, and inflammation in the liver. Nevertheless, simultaneous administration of GSPE resumed the declined serum hepatic enzyme activities and histological abnormalities in PFOS-exposed mice. Furthermore, GSPE supplementation reduced the contents of triglyceride (TG) and total cholesterol (TC) and expression of lipid metabolism-associated genes CD36 and fatty acid-binding protein 4 (FABP4) in the liver of mice treated with PFOS. Moreover, GSPE suppressed the generation of lipid peroxidative product malondialdehyde and restored the activity of superoxide dismutase in the liver of PFOS-exposed mice. In addition, GSPE repressed the PFOS-induced hepatic overproduction of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Our results demonstrate that GSPE attenuates PFOS-caused steatohepatitis in mice by regulating lipid metabolism, oxidative stress, and inflammatory response.

Abiraterone and MDV3100 inhibits the proliferation and promotes the apoptosis of prostate cancer cells through mitophagy.

BACKGROUND: Abiraterone and MDV3100 are two effective anticancer agents for prostate cancer, however, the mechanism of their downstream action remains undefined. METHODS: A dual fluorescent biosensor plasmid was transfected in LNCaP cells to measure mitophagy. The DNA of LNCaP cells was extracted and performed with quantitative real-time PCR to detect mitochondrial DNA copy number. JC-1 staining was utilized to detect the mitochondrial membrane potential and electron microscope was performed to analyze mitochondrial morphology. Moreover, the protein levels of mitochondrial markers and apoptotic markers were detected by western blot. At last, the proliferation and apoptosis of LNCaP cells were analyzed with CCK-8 assay and flow cytometry after abiraterone or MDV3100 treatment. RESULTS: Mitophagy was induced by abiraterone and MDV3100 in LNCaP cells. The low expression level of mitochondrial DNA copy number and mitochondrial depolarization were further identified in the abiraterone or MDV3100 treatment groups compared with the control group. Besides, severe mitochondria swelling and substantial autophagy-lysosomes were observed in abiraterone- and MDV3100-treated LNCaP cells. The expression of mitochondria-related proteins, frataxin, ACO2 and Tom20 were significantly downregulated in abiraterone and MDV3100 treated LNCaP cells, whereas the expression level of inner membrane protein of mitochondria (Tim23) was significantly upregulated in the same condition. Moreover, the proliferation of LNCaP cells were drastically inhibited, and the apoptosis of LNCaP cells was increased in abiraterone or MDV3100 treatment groups. Meanwhile, the addition of mitophagy inhibitor Mdivi-1 (mitochondrial division inhibitor 1) could conversely elevate proliferation and constrain apoptosis of LNCaP cells. CONCLUSIONS: Our results prove that both abiraterone and MDV3100 inhibit the proliferation, promote the apoptosis of prostate cancer cells through regulating mitophagy. The promotion of mitophagy might enhance the efficacy of abiraterone and MDV3100, which could be a potential strategy to improve chemotherapy with these two reagents.

Androgen upregulates the palmitoylation of eIF3L in human prostate LNCaP cells.

Background: Prostate cancer is the second leading cause of cancer-related deaths in Western countries. Most patients diagnosed with advanced prostate cancer can be treated with the main treatment: androgen deprivation therapy (ADT). The androgen receptor (AR) signaling axis plays a pivotal role in the progression of prostate cancer. However, most patients can ultimately progress to the castration-resistant prostate cancer (CRPC) stage within 2 years. At this stage, drugs targeting the AR signaling axis, including enzalutamide and abiraterone acetate, cannot prevent the progression of prostate cancer, thus predicting a poor prognosis. The molecular mechanism lies in the aberrant AR reactivation, which exhibits an adaptive response to ADT, such as the presence of AR splice variants. Thus, CRPC treatment remains a challenge. Purpose: In addition to the AR axis, a mechanism leading to this progression should be determined. The present study mainly compared palmitoylated proteins between androgen-treated LNCaP cells and non-treated LNCaP cells by palmitoylome profiling, to illustrate the changes at proteomic levels. Materials and methods: To screen the androgen-induced palmitoylated proteins, we conducted proteomic experiments using clickable palmitate probe (Alk-C16) between three individual pairs of androgen-treated and non-treated LNCaP cells. Results: We identified 4351 unique peptides corresponding to 835 proteins, among them a number of these identified proteins were palmitoylated proteins, particularly eIF3L. Androgen treatment significantly increased the palmitoylation level of eIF3L, an individual subunit of eIF3. As an initiation factor, eIF3L plays a pivotal role in the translation of mRNAs encoding growth-promoting proteins by enhancing translation rates, thus controlling cell proliferation. Conclusion: In this study, we demonstrated that the regulation of eIF3L palmitoylation may provide new directions for the therapy of prostate cancer. Moreover, the increased level of androgen-induced eIF3L may be used as a biomarker for the diagnosis of early-stage prostate cancer.

Gestational exposure to acrylamide inhibits mouse placental development in vivo.

Acrylamide, a carcinogen and neurotoxic substance, recently has been discovered in various heat-treated carbohydrate-rich foods. The aim of this study was to investigate the effects of acrylamide exposure on placental development. Pregnant mice received acrylamide by gavage at dosages of 0, 10, and 50 mg/kg/day from gestational days (GD) 3 until GD 8 or GD 13. The results showed that acrylamide feeding significantly decreased the numbers of viable embryos and increased the numbers of resorbed embryos on GD 13. Acrylamide exposure reduced the absolute and relative weight of placentas and embryos, and inhibited the development of ectoplacental cone (EPC) and placenta, as shown by the atrophy of EPC and reduced placental area. Acrylamide markedly reduced the numbers of labyrinth vessels. Expression levels of most placental key genes such as Esx1, Hand1, and Hand2 mRNA dramatically decreased in acrylamide-treated placentas. Furthermore, acrylamide treatment inhibited proliferation and induced apoptosis of placentas, as shown by decreased Ki67-positive cells and Bcl-2 protein, and increased the expression of Bax, cleaved-caspase-3, and cleaved-caspase-8 proteins. In conclusion, our results indicated that gestational exposure to acrylamide inhibits placental development through dysregulation of placental key gene expression and labyrinth vessels, suppression of proliferation, and apoptosis induction in mice.

Impact of different color fiber sleeves on beam hazards of 532-nm laser and vaporization efficiency.

The 532-nm laser has become increasingly popular for the treatment of urologic diseases. However, laser beam will pose significant hazards for the health of surgeons. In order to reduce beam hazards during surgery, we compared the beam hazards of laser fiber with black sleeves to the traditional fiber with transparent sleeves, and the vaporization efficiency. A total of 18 porcine kidney specimens were vaporized in normal saline at a room temperature under 532-nm laser delivered through a 760-µm core diameter side firing fiber. Two groups were divided according to the color of fiber sleeves: the transparent and the black. Each group was then divided into another three subgroups by laser power: the 80 W group, the 120 W group, and the 160 W group. The beam hazard was evaluated by light intensity measured in a sector area at a distance of 0 m, 0.5 m, and 1 m from the irradiation center. The vaporization efficiency was measured by the vaporization groove depth under the working power of 80 W, 120 W, and 160 W with a working distance of 5 mm and irradiation time of 10 s. The light intensity measured in the black fiber sleeve group is significantly lower than that in the transparent one (P < 0.01), regardless of the measuring distance (0 m, 0.5 m, and 1.0 m) and laser power (80 W, 120 W, and 160 W). No statistical difference was found on the vaporization efficiency between the groups protected by fiber sleeves of different colors (transparent/black, p > 0.05). Compared to the traditional transparent fiber sleeves, more beam hazards will be reduced in the operative region with the protection of black fiber sleeves, especially those from the irradiation center. The vaporization efficiency is not affected by the color of fiber sleeves. Such findings may offer a completely new idea for the protection of surgeons in surgeries with 532-nm lasers.

Spatial Intratumor Genomic Heterogeneity within Localized Prostate Cancer Revealed by Single-nucleus Sequencing.

BACKGROUND: Prostate adenocarcinoma (PCa) is a complex genetic disease, and the implementation of personalized treatment in PCa faces challenges due to significant inter- and intrapatient tumor heterogeneities. OBJECTIVE: To systematically explore the genomic complexity of tumor cells with different Gleason scores (GSs) in PCa. DESIGN, SETTING, AND PARTICIPANTS: We performed single-cell whole genome sequencing of 17 tumor cells from localized lesions with distinct GS and matched four normal samples from two prostatectomy patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All classes of genomic alterations were identified, including substitutions, insertions/deletions, copy number alterations, and rearrangements. RESULTS AND LIMITATIONS: Significant spatial, intra- and intertumoral heterogeneities were observed at the cellular level. In the patient 1, all cells shared the same TP53 driver mutation, implying a monoclonal origin of PCa. In the patient 2, only a subpopulation of cells contained the TP53 driver mutation, whereas other cells carried different driver mutations, indicating a typical polyclonal model with separate clonal cell expansions. The tumor cells from different sides of prostate owned various mutation patterns. Considerable neoantigens were predicted among different cells, implying unknown immune editing components helping prostate tumor cells escaping from immune surveillance. CONCLUSIONS: There is a significant spatial genomic heterogeneity even in the same PCa patient. Our study also provides the first genome-wide evidence at single-cell level, supporting that the origin of PCa could be either polyclonal or monoclonal, which has implications for treatment decisions for prostate cancer. PATIENT SUMMARY: We reported the first single-cell whole genomic data of prostate adenocarcinoma (PCa) from different Gleason scores. Identification of these genetic alterations may help understand PCa tumor progression and clonal evolution.

The Urinary Sarcosine/Creatinine Ratio is a Potential Diagnostic and Prognostic Marker in Prostate Cancer.

BACKGROUND The aim of this study was to evaluate the role of the urinary sarcosine/creatinine ratio in the diagnosis and prognosis of prostate cancer, using a sarcosine oxidase assay. MATERIAL AND METHODS Urine samples were obtained from 203 patients with benign prostate hyperplasia (BPH) and 209 patients with prostate cancer. Levels of urinary sarcosine were measured using the sarcosine oxidase method. The urinary sarcosine/creatinine ratios were compared between the group of patients with BPH and the patients with prostate cancer. In the two patients groups, the urinary sarcosine/creatinine ratio was compared with the measurement of serum prostate-specific antigen (PSA) and the free/total (F/T) PSA ratio. Correlations between of the urinary sarcosine/creatinine ratio and the Gleason grade and stage of prostate cancer were analyzed. RESULTS There was a significant difference between the urinary sarcosine/creatinine ratio in the BPH group and prostate cancer group (P<0.01), which was independent of serum PSA. The receiver-operating characteristic (ROC) curve, and area under the curve (AUC) for the urinary sarcosine/creatinine ratio was significantly higher compared with the serum PSA and the F/T PSA ratio. There was a significant difference in the urinary sarcosine/creatinine ratio in patients with prostate cancer with Gleason score ≤6, 7, and ≥8, and between patients with metastatic and non-metastatic prostate cancer. CONCLUSIONS The urinary sarcosine/creatinine ratio was a diagnostic indicator of prostate cancer, for patients with a serum PSA level <10 ng/ml, and correlated with the Gleason score and with the presence of metastases (stage) of prostate cancer.

Exposure to 2,4-dichlorophenoxyacetic acid induces oxidative stress and apoptosis in mouse testis.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide. It has been associated with a variety of toxicities in rodents. In this study, male mice were orally administered 2,4-D at 50, 100 or 200mg/kg/day to investigate testicular toxicity and the possible mechanisms of action. Exposure to 2,4-D at high concentrations (100 and 200mg/kg/day) for 14 consecutive days caused spermatogenic disruption and seminiferous epithelial destruction. Furthermore, 2,4-D administration (100 and 200mg/kg/day) increased the formation of the lipid peroxidation product malondialdehyde and decreased activities of the antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, 2,4-D exposure up-regulated the expression of p53 and Bax protein and down-regulated the expression of Bcl-2 protein in the testis. These results demonstrate that oxidative stress and apoptosis may be involved in testicular toxicity induced by high concentrations of 2,4-D in mice.

Maternal exposure to perfluorooctanoic acid inhibits luteal function via oxidative stress and apoptosis in pregnant mice.

Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated compound, which has been reported to exert adverse effect on the pregnancy. However, whether it is associated with alteration of luteal function remains unknown. Mice were administered PFOA by gavage from gestational days (GD) 1-7 or 13. PFOA treatment did not significantly affect numbers of embryo implantation. Nevertheless, on GD 13, 10mg/kg PFOA treatment significantly increased numbers of resorbed embryo. Furthermore, PFOA exposure markedly reduced serum progesterone levels but did not affect estradiol levels. Treatment also showed concomitant decreases in transcript levels for key steroidogenic enzymes, and reduced numbers and sizes of corpora lutea. In addition, PFOA administration inhibited activities of superoxide dismutase and catalase, and increased generation of hydrogen peroxide and malondialdehyde, and down-regulated level of Bcl-2 and up-regulated p53 and BAX proteins. In conclusion, PFOA exposure significantly inhibits luteal function via oxidative stress and apoptosis in pregnant mice.