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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS1988

Zinc, copper, and nitrogen balances during bed rest and fluoride supplementation in healthy adult males

The effects of bed rest and fluoride supplementation on zinc, copper, and nitrogen balances and Zn and Cu serum levels were measured in 15 healthy males. Subjects aged 19-54 y remained on a metabolic research ward for 10 wk. During weeks 1-5, subjects were ambulatory. During wks 6-10 they remained in continuous bed rest. During weeks 3-10 nine subjects received 10 or 20 mg F/d as sodium fluoride. Daily urine and weekly fecal composites were made and biweekly fasting blood samples were taken. Dietary intakes were 1.40 +/- 0.17 mg Cu/d (22.0 +/- 2.7 mumol Cu/d), 10.82 +/- 0.49 mg Zn/d (165.6 +/- 7.6 mumol Zn/d), and 14.27 +/- 0.23 g N/d (1019 +/- 16 mmol N/d). Bed rest increased urinary Zn and N excretions and fecal Zn excretions and decreased Zn balance (p less than 0.05) whereas Cu balance was unchanged. During bed rest, F supplementation increased Zn and N balances compared with untreated control subjects (p less than 0.05). These results are compatible with bone and muscle atrophy during bed rest and increased bone formation with F supplementation.

Clinical Trial↗
NASA NTRS2005

Vitamin E provides protection for bone in mature hindlimb unloaded male rats

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

NASA Discipline Musculoskeletal↗
DOE OSTI2019

Detection of SRY‐positive46,XX male syndrome by the analysis of cell‐free fetal DNA via non‐invasive prenatal testing

Abstract We report a new case of 46,XX male syndrome that was detected following an anomalous result by non‐invasive prenatal testing (NIPT) and a discrepancy between the fetal karyotype and the ultrasonographic investigation. With the increasing use of NIPT, more gender discordances can be identified prenatally and be amenable to early therapy.

De Falco, Luigia↗
DOE OSTI2023

The effect of reducing dietary lipid and food availability on precocious male maturation in Chinook Salmon: A production-scale hatchery experiment

Abstract Objective Age of maturation in Chinook Salmon Oncorhynchus tshawytscha is phenotypically plastic, influenced by both genotype and environmental factors, including the availability and composition of the diet. Salmon hatchery programs often rear fish under accelerated growth regimes using high-lipid diets that can result in earlier age at maturity, including increased prevalence of age-2 males (minijacks). The goal of this investigation was to compare alternative dietary regimes to mitigate for this shift in age at maturity in hatchery-reared Umatilla River fall Chinook Salmon. Methods Juvenile fish were reared at Bonneville Hatchery, Oregon, under four dietary treatments across four replicate brood years. Dietary treatments included two feeding frequencies (standard [fed 7 days/week] and reduced [fed 4 days/week]) and two dietary lipid levels (standard [18%] and reduced [12%]) in a 2 × 2 factorial design. Dietary treatments were applied for approximately 9 months, beginning in March (a month after fry emergence) and lasting until December of the first year, after which all fish were reared on the standard feeding regime (7 days–18%) until the time of release the following spring as yearlings. Result We observed significant interannual variation in the proportion of minijacks produced among dietary treatments. For all brood years, decreasing the feeding frequency from 7 to 4 days/week reduced the proportion minijacks by 35.9%, and lowering dietary lipid from 18% to 12% reduced the proportion minijacks by 30%. The combined effects of reducing the feeding frequency and lowering dietary lipid were additive, reducing the proportion minijacks by 65.5% compared to the standard rearing regime. Growth and energetic indices were monitored throughout and confirmed findings from previous laboratory-based studies indicating that physiological status 10–12 months prior to spawn timing is important for the “decision” to mature. Conclusion Results of this investigation provide useful insights for optimizing rearing regimes for the Umatilla River program and other Chinook Salmon hatchery programs.

Harstad, Deborah L. (ORCID:0000000202676085)↗
DOE OSTI2019

Multimodality imaging of the male urethra: trauma, infection, neoplasm, and common surgical repairs

Objective: The aim of this article is to describe the indications and proper technique for RUG and MRI, their respective image findings in various disease states, and the common surgical techniques and imaging strategies employed for stricture correction. Results: Because of its length and passage through numerous anatomic structures, the adult male urethra can undergo a wide array of acquired maladies, including traumatic injury, infection, and neoplasm. For the urologist, imaging plays a crucial role in the diagnosis of these conditions, as well as complications such as stricture and fistula formation. While retrograde urethrography (RUG) and voiding cystourethrography (VCUG) have traditionally been the cornerstone of urethral imaging, MRI has become a useful adjunct particularly for the staging of suspected urethral neoplasm, visualization of complex posterior urethral fistulas, and problem solving for indeterminate findings at RUG. Conclusions: Familiarity with common urethral pathology, as well as its appearance on conventional urethrography and MRI, is crucial for the radiologist in order to guide the treating urologist in patient management.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

The Role of Interventional Radiology in the Diagnosis and Management of Male Impotence

Erectile dysfunction (ED) is defined as the persistent inability to reach or maintain penile rigidity enough for sexual satisfaction. Nearly 30% of the men between ages 40 and 70 years are affected by ED. A variety of pathologies, including neurological, psychological, or endocrine disorders and drug side effects, may incite ED. A commonly identified cause of ED is vascular disease. Initial diagnostic workup includes a detailed physical examination and laboratory tests. Whilst duplex ultrasound is considered the first-line diagnostic modality, intra-arterial digital subtraction angiography is still considered the 'gold standard' for the diagnosis of arteriogenic impotence. Percutaneous endovascular treatment may be offered in patients with vasculogenic ED that has failed to respond to oral medical therapy as an alternative to penile prosthesis or open surgical repair. In arteriogenic ED balloon angioplasty of the aorto-iliac axis, and in veno-occlusive ED, percutaneous venous ablation using various embolization materials has been reported to be safe and to improve sexual performance. Recently, the ZEN study investigated the safety and feasibility of drug-eluting stents for the treatment of arteriogenic ED attributed to internal pudendal artery stenosis with promising preliminary results. This manuscript highlights the role of interventional radiology in the diagnosis and minimally invasive treatment of male impotence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Blood Pressure Changes After Exposures Increasing Angiotensin-Converting Enzyme Activity and After Its Normalization with Dihydroquercetin in Male Wistar Rats

Changes in BP and HR were assessed after exposures increasing activity of angiotensin-converting enzyme: ionizing radiation, NO synthase inhibitor (L-NAME), and dexamethasone. Effects of dihydroquercetin and angiotensin-converting enzyme inhibitor enalapril on activity of this enzyme, BP, and HR were also evaluated under these exposures. Wistar male rats were subjected to X-ray irradiation in a dose of 2.5 Gy. Angiotensin-converting enzyme activity in the aorta sections was determined by Hip-His-Leu hydrolysis. BP and HR were recorded using a non-invasive tail-cuff method and PowerLab 8/35 software. BP and HR were not altered with the increase in activity of angiotensin-converting enzyme after irradiation. In case of prolonged (7 days) treatment with NO synthase inhibitor and dexamethasone, the increase in enzyme activity was accompanied by elevation of BP and, in the case of NO synthase inhibitor, HR reduction. Dihydroquercetin normalized the enzyme activity and lowered BP, but not to the normal level. Enalapril normalized BP, increased by NO synthase inhibitor solution intake; at the same time, the angiotensinconverting enzyme activity decreased more than 2-fold in comparison with the normal.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Mouse model of chorea-acanthocytosis exhibits male infertility caused by impaired sperm motility as a result of ultrastructural morphological abnormalities in the mitochondrial sheath in the sperm midpiece

Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60–61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Immunocytochemical study revealed that chorein-like immunoreactivity is abundant only in the midpiece, mitochondria-rich region, of the sperm of wild type mice. They showed no significant differences from wild types in terms of the adenosine 5′-triphosphate (ATP) concentration of their sperm, sperm count, or sexual activity. Electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from ChAc-model mice. These results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Effects of mobile phone exposure on metabolomics in the male and female reproductive systems

Highlights: • Long-term exposure to EMF decreases sperm motility and fertilization. • Effects of EMF emitted from mobile phones are related to protein synthesis. • Oxidative stress based EMF exposure modulates nitric oxide level in the germ cells. • Oxidative stress based EMF exposure inhibits antioxidant mechanisms in the germ cells. With current advances in technology, a number of epidemiological and experimental studies have reported a broad range of adverse effects of electromagnetic fields (EMF) on human health. Multiple cellular mechanisms have been proposed as direct causes or contributors to these biological effects. EMF-induced alterations in cellular levels can activate voltage-gated calcium channels and lead to the formation of free radicals, protein misfolding and DNA damage. Because rapidly dividing germ cells go through meiosis and mitosis, they are more sensitive to EMF in contrast to other slower-growing cell types. In this review, possible mechanistic pathways of the effects of EMF exposure on fertilization, oogenesis and spermatogenesis are discussed. In addition, the present review also evaluates metabolomic effects of GSM-modulated EMFs on the male and female reproductive systems in recent human and animal studies. In this context, experimental and epidemiological studies which examine the impact of mobile phone radiation on the processes of oogenesis and spermatogenesis are examined in line with current approaches.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2012

The Impact of Post-Mastectomy Radiation Therapy on Male Breast Cancer Patients-A Case Series

Objective: To assess the impact of radiation management on male breast cancer (MBC) at London Regional Cancer Program (LRCP). Methods and Materials: Men with a diagnosis of breast cancer referred to LRCP were reviewed. The seventh American Joint Committee on Cancer staging system was used. Patients treated with and without post-mastectomy radiation therapy (PMRT) were analyzed. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. Survival estimates were obtained using Kaplan-Meier methodology. Results: From January 1977 to December 2006, 81 men had invasive ductal carcinoma. The median age was 65 (range, 35-87 years). There were 15 Stage I, 40 Stage II, 20 Stage III, and 6 Stage IV patients. Median follow-up time was 46 months (range, 1-225 months). Of the 75 patients treated with curative intent, 29 did not receive PMRT and 46 completed PMRT. Patients who received PMRT demonstrated no benefit in overall survival (p = 0.872) but significantly better local recurrence free survival (p < 0.001) compared with those who did not receive RT. There was trend toward improving locoregional recurrence with PMRT in patients with high-risk features (node-positive, advanced stage, and {<=}2 mm or unknown surgical margin). The median, 5-year, and 10-year disease-free survival and overall survival for the 75 patients were 77.7 months, 66.3%, 32.7%, and 91.2 months, 73.9%, and 36.6%, respectively. Conclusion: The experience at LRCP suggests that high-risk MBC patients should consider PMRT to improve their chance of local recurrence-free survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T{sub 3} and T{sub 4} in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100 mg/kg body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H{sub 2}O{sub 2}, hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP. -- Highlights: Black-Right-Pointing-Pointer DEHP treatment significantly decreased serum insulin and testosterone levels. Black-Right-Pointing-Pointer Increased ROS and decreased glucose uptake were observed in DEHP treated animals. Black-Right-Pointing-Pointer Impaired insulin signaling in gastrocnemius muscle was observed in DEHP treatment. Black-Right-Pointing-Pointer Vitamins C and E alter ROS, glucose uptake, oxidation and insulin signaling molecules.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G{sub 2}/M arrest and appearance of a distinctive SubG{sub 1} peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced activities of caspases 3 and 9.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Kinetics of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate in blood and of DEHP metabolites in urine of male volunteers after single ingestion of ring-deuterated DEHP

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is suspected to induce antiandrogenic effects in men via its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, there is only little information on the kinetic behavior of DEHP and its metabolites in humans. The toxikokinetics of DEHP was investigated in four male volunteers (28–61 y) who ingested a single dose (645 ± 20 μg/kg body weight) of ring-deuterated DEHP (DEHP-D{sub 4}). Concentrations of DEHP-D{sub 4}, of free ring-deuterated MEHP (MEHP-D{sub 4}), and the sum of free and glucuronidated MEHP-D{sub 4} were measured in blood for up to 24 h; amounts of the monoesters MEHP-D{sub 4}, ring-deuterated mono(2-ethyl-5-hydroxyhexyl) phthalate and ring-deuterated mono(2-ethyl-5-oxohexyl) phthalate were determined in urine for up to 46 h after ingestion. The bioavailability of DEHP-D{sub 4} was surprisingly high with an area under the concentration-time curve until 24 h (AUC) amounting to 50% of that of free MEHP-D{sub 4}. The AUC of free MEHP-D{sub 4} normalized to DEHP-D{sub 4} dose and body weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D{sub 4} even 50 and 100 times higher than the corresponding AUC/D values obtained earlier in rat and marmoset, respectively. Time courses of the compounds in blood and urine of the volunteers oscillated widely. Terminal elimination half-lives were short (4.3–6.6 h). Total amounts of metabolites in 22-h urine are correlated linearly with the AUC of free MEHP-D{sub 4} in blood, the parameter regarded as relevant for risk assessment. -- Highlights: ► After DEHP intake, DEHP and MEHP in blood show oscillating time courses. ► Dose-related blood levels of DEHP are 50 times higher in humans than in rats. ► Dose-related blood levels of free MEHP are 2 times higher in humans than in rats. ► Elimination of DEHP and its metabolites is short with half-lives of 4.3-6.6 h.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Fluorochemicals used in food packaging inhibit male sex hormone synthesis

Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact materials (FCMs) of paper and board and have recently been detected in 57% of investigated materials. Human exposure occurs as PAPS have been measured in blood; however knowledge is lacking on the toxicology of PAPS. The aim of this study was to elucidate the effects of six fluorochemicals on sex hormone synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2 FTOH) were tested. Hormone profiles, including eight steroid hormones, generally showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH led to decreases in androgens (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R steroidogenesis assay. Decreases were observed for progesterone and 17-OH-progesterone as well. These observations indicated that a step prior to progestagen and androgen synthesis had been affected. Gene expression analysis of StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol transport to the inner mitochondria. Cortisol, estrone and 17β-estradiol levels were in several cases increased with exposure. In accordance with these data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH exposures indicating that this is a contributing factor to the decreased androgen and the increased estrogen levels. Overall, these results demonstrate that fluorochemicals present in food packaging materials and their metabolites can affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression leading to lower androgen and higher estrogen levels. -- Highlights: ► Fluorochemicals found in 57% of paper and board food packaging were tested. ► Collectively six fluorochemicals were tested for antiandrogenic potential in vitro. ► Three out of six tested fluorochemicals inhibited synthesis of male sex hormones. ► Generally, levels of estrogens and cortisol stayed unaffected or increased. ► The effect on steroid synthesis was specific on gene expression of Bzrp and CYP19.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Aldosterone induces fibrosis, oxidative stress and DNA damage in livers of male rats independent of blood pressure changes

Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague–Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure. To investigate the impact of oxidative stress, the antioxidant tempol was administered. Aldosterone induced fibrosis, detected histopathologically, and by expression analysis of the fibrosis marker, α-smooth muscle actin. Further, the mRNA amount of the profibrotic cytokine TGF-β was increased significantly. Fibrosis could be reduced by scavenging reactive oxygen species, and also by blocking the mineralocorticoid receptor. Furthermore, aldosterone treatment caused oxidative stress and DNA double strand breaks in livers, as well as the elevation of DNA repair activity. An increase of the transcription factor Nrf2, the main regulator of the antioxidative response could be observed, and of its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. All these effects of aldosterone were prevented by spironolactone and tempol. Already after 4 weeks of treatment, aldosteroneinfusion induced fibrosis in the liver. This effect was independent of elevated blood pressure. DNA damage caused by aldosterone might contribute to fibrosis progression when aldosterone is chronically increased. - Highlights: • Aldosterone has direct profibrotic effects on the liver independent of blood pressure. • Fibrosis is mediated by the mineralocorticoid receptor and oxidative stress. • Aldosterone induces transcription factor Nrf2 and Nrf2-regulated genes in the liver. • DNA damage caused by aldosterone might contribute to fibrosis progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile

We investigated the associations between environmental exposure to lead and a repertoire of cytokines in seminal plasma of males with normal semen profile according to the WHO criteria. Based on the median lead concentration in seminal plasma, 65 samples were divided into two groups: low (LE) and high exposure to lead (HE). Differences in semen volume and the pH, count, motility and morphology of sperm cells were not observed between the examined groups. The total oxidant status value and the level of protein sulfhydryl groups as well as the activities of manganese superoxide dismutase and catalase were significantly higher in the HE group, whereas the total antioxidant capacity value and the activities of glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10, IL-12, and TNF-α levels were significantly higher in the HE group compared with the LE group. Environmental exposure to lead is sufficient to induce oxidative stress in seminal plasma and to modulate antioxidant defense system. - Highlights: • Lead induces oxidative stress in seminal plasma in human. • Lead modulates antioxidant defense system in seminal plasma in human. • Lead does not change a Th1/Th2 imbalance in seminal plasma in human.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice

Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is a soluble lipid-binding protein that transports phosphatidylcholine (PC) between cellular membranes. To better understand the protective metabolic effects associated with hepatic PC-TP, we generated a hepatocyte-specific PC-TP knockdown (L-Pctp -/- ) in male mice, which gains less weight and accumulates less liver fat compared to wild-type mice when challenged with a high-fat diet. Hepatic deletion of PC-TP also reduced adipose tissue mass and decreases levels of triglycerides and phospholipids in skeletal muscle, liver and plasma. Gene expression analysis suggest that the observed metabolic changes are related to transcriptional activity of peroxisome proliferative activating receptor (PPAR) family members. An in-cell protein complementation screen between lipid transfer proteins and PPARs uncovered a direct interaction between PC-TP and PPARδ that was not observed for other PPARs. We confirmed the PC-TP– PPARδ interaction in Huh7 hepatocytes, where it was found to repress PPARδ-mediated transactivation. Mutations of PC-TP residues implicated in PC binding and transfer reduce the PC-TP-PPARδ interaction and relieve PC-TP-mediated PPARδ repression. Reduction of exogenously supplied methionine and choline reduces the interaction while serum starvation enhances the interaction in cultured hepatocytes. Together our data points to a ligand sensitive PC-TP– PPARδ interaction that suppresses PPAR activity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cells

Silica nanoparticles (NP) is one of the most commonly used nanomaterials with potential health hazards. However, the effects of Silica NP on germ cells and the underlying mechanisms are still unclear. In this study, GC-2 and TM-4, which are two different types of male germ cells were exposed to Silica NP for 24h and then general cytotoxicity and multi-parameter cytotoxicity were evaluated. Our results showed that Silica NP could induce apoptosis in GC-2 cells. Transmission electron microscopy (TEM) results showed that Silica NP was localized in the lysosomes of GC-2 cells. High content screening (HCS) showed that Silica NP exposure could increased cell permeabilization and decreased mitochondrial membrane potential in GC-2 cells. The mRNA and protein levels of apoptosis markers (Bax, Caspase-3, Caspase-9) in GC-2 cells were significantly increased, while Bcl-2 was decreased. Accordingly, the expression level of miR-98, which can regulate Caspase-3, was significantly decreased. Huwe1, the host gene of miR-98, was positively associated with miR-98 expression after Silica NP exposure. Dual luciferase reporter assay suggested that miR-98 directly targets Caspase-3. These results suggest that Silica NP induces apoptosis via loss of mitochondrial membrane potential and Caspase-3 activation, while miR-98 plays key role in modulating this effect.

Science & Technology - Other Topics↗