Dynamics and necessity of SIRT1 for maternal-zygotic transition.

Dynamic changes in maternal‒zygotic transition (MZT) require complex regulation of zygote formation, maternal transcript decay, embryonic genome activation (EGA), and cell cycle progression. Although these changes are well described, some key regulatory factors are still elusive. Sirtuin-1 (SIRT1), an NAD-dependent histone deacetylase, is a versatile driver of MZT via its epigenetic and nonepigenetic substrates.

Autologous Mesenchymal Stromal Cells Immobilized in Plasma-Based Hydrogel for the Repair of Articular Cartilage Defects in a Large Animal Model.

The treatment of cartilage defects in trauma injuries and degenerative diseases represents a challenge for orthopedists. Advanced mesenchymal stromal cell (MSC)-based therapies are currently of interest for the repair of damaged cartilage. However, an approved system for MSC delivery and maintenance in the defect is still missing.

Effect of Bisphenol S on testicular tissue after low-dose lactation exposure.

Exposure to endocrine disruptors such as bisphenols, can lead to and be the explanation for idiopathic infertility. In our study, we assessed the effect of exposure to bisphenol S (BPS) via breast milk on the testicular tissue health of adult male mice. Lactating dams were exposed to BPS through drinking water (0.

Evidence of endogenously produced hydrogen sulfide (HS) and persulfidation in male reproduction.

Persulfidation contributes to a group of redox post-translational modifications (PTMs), which arise exclusively on the sulfhydryl group of cysteine as a result of hydrogen sulfide (HS) action. Redox-active molecules, including HS, contribute to sperm development; therefore, redox PTMs represent an extremely important signalling pathway in sperm life. In this path, persulfidation prevents protein damage caused by irreversible cysteine hyperoxidation and thus maintains this signalling pathway.

Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize.

Deficient sperm motility is a frequent cause of the age-related male sub-/infertility. Since the protein sirtuin 1 (SIRT1) develops anti-aging action and participates in sperm motility and ATP synthesis in mitochondria, we investigated its role in the acquisition of hyperactivated motility during capacitation. For this, the dynamics of sperm subpopulations were studied, using males of Sirt1 heterozygous mutant mice.

Nursing Exposure to Bisphenols as a Cause of Male Idiopathic Infertility.

Idiopathic infertility is a serious problem, which can be caused and explained by exposure to endocrine disruptors, such as bisphenols. In our study, we studied transactional exposure to bisphenol and its effects on newborn male mice throughout their reproductive life. Newborn male mice were exposed to bisphenol S and bisphenol F through maternal milk from post-natal day 0 to post-natal day 15 at concentrations of 0.

Exposure to alternative bisphenols BPS and BPF through breast milk: Noxious heritage effect during nursing associated with idiopathic infertility.

There is increasing evidence that bisphenols BPS and BPF, which are analogues of BPA, have deleterious effects on reproduction even at extremely low doses. Indirect exposure via the maternal route (i.e.

Targeting CD34 cells of the inflamed synovial endothelium by guided nanoparticles for the treatment of rheumatoid arthritis.

Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes.

Flavones Inhibit the Activity of AKR1B10, a Promising Therapeutic Target for Cancer Treatment.

AKR1B10 is an NADPH-dependent reductase that plays an important function in several physiological reactions such as the conversion of retinal to retinol, reduction of isoprenyl aldehydes, and biotransformation of procarcinogens and drugs. A growing body of evidence points to the important role of the enzyme in the development of several types of cancer (e.g.

Human dehydrogenase/reductase (SDR family) member 8 (DHRS8): a description and evaluation of its biochemical properties.

Dehydrogenase/reductase (SDR family) member 8 (DHRS8, SDR16C2) belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, one of the largest enzyme groups. In addition to the well-known members which participate in the metabolism of important eobiotics and xenobiotics, this superfamily contains many poorly characterized proteins. DHRS8 is a member of the Multisubstrate NADP(H)-dependent SDR16C family, which generally contains insufficiently described enzymes.

Pharmacokinetic interactions of breast cancer chemotherapeutics with human doxorubicin reductases.

Paclitaxel (PTX), docetaxel (DTX), 5-fluorouracil (5-FU), cyclophosphamide (CYC) or tamoxifen (TMX) are combined with doxorubicin (DOX) in first-line chemotherapy regimens that are indicated for breast cancer patients. Although the efficacies of these drugs in combination treatments have been demonstrated in clinical practice, their possible interference with DOX metabolism has not been described in detail to date. In the present study, we investigated the possible interactions of human carbonyl reducing enzymes with 5-FU, PTX, DTX, CYC and TMX.

Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3).

Dehydrogenase/reductase (SDR family) member 3 (DHRS3), also known as retinal short-chain dehydrogenase/reductase (retSDR1) is a member of SDR16C family. This family is thought to be NADP(H) dependent and to have multiple substrates; however, to date, only all-trans-retinal has been identified as a DHRS3 substrate. The reductive reaction catalysed by DHRS3 seems to be physiological, and recent studies proved the importance of DHRS3 for maintaining suitable retinoic acid levels during embryonic development in vivo.

Isoquinoline alkaloids as a novel type of AKR1C3 inhibitors.

AKR1C3 is an important human enzyme that participates in the reduction of steroids and prostaglandins, which leads to proliferative signalling. In addition, this enzyme also participates in the biotransformation of xenobiotics, such as drugs and procarcinogens. AKR1C3 is involved in the development of both hormone-dependent and hormone-independent cancers and was recently demonstrated to confer cell resistance to anthracyclines.

Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state.

Diabetic ketoacidosis and the hyperglycemic hyperosmolar state are the most serious complications of diabetic decompensation and remain associated with excess mortality. Insulin deficiency is the main underlying abnormality. Associated with elevated levels of counterregulatory hormones, insulin deficiency can trigger hepatic glucose production and reduced glucose uptake, resulting in hyperglycemia, and can also stimulate lipolysis and ketogenesis, resulting in ketoacidosis.

Bioassay-directed chemical analysis and detection of mutagenicity in ambient air of the coke oven.

In the present study, we summarize the results of studies on the mutagenic potential of the main fractions and subfractions of extractable organic material (EOM) in the ambient air at the workplaces of the coke oven. The objective of our experiments was to apply the Bioassay-Directed Chemical Analysis (with the use of the Ames test) for the identification of the differences in the mutagenicity of these fractions, in relationship to the complex mixture of EOM in occupational air. From the evaluation of results, it is possible to deduce the following conclusions: (1) The comparison of the mutagenicity in the main fractions (basic, acidic, neutral) demonstrates the existence of differences in mutagenic potential.

Long-term use of intramuscular insulin therapy in a type I diabetic patient with subcutaneous insulin resistance.

We studied a 26-year-old Type 1 diabetic patient who experienced recurrent episodes of ketoacidosis and who was unresponsive to subcutaneous insulin, but normally responsive to intravenous insulin as demonstrated by insulin challenge test. Attempts at intravenous and intraperitoneal insulin administration were complicated by recurrent septicaemia. We therefore investigated the hypoglycaemic effect of intramuscular insulin administration in this patient.

Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo.

Vitamin D is essential for normal insulin secretion in vivo and in vitro. The differential effect of calcium and of the vitamin D endocrine system in the insulin response to secretagogues is still a subject of debate. To study the roles of calcium and the vitamin D system in the in vivo insulin response, GTT and insulin sensitivity tests were conducted in rats presenting vitamin D depletion and hypocalcemia or vitamin D depletion supplemented with calcium alone for 3, 7, or 14 days, vitamin D3 (6.

[Detection of antibodies to submitochondrial particles, F1-ATPase complex and liver specific lipoprotein in liver diseases using ELISA].

ELISA was elaborated for the determination of antibodies against liver antigen complexes--submitochondrial particles, F1-ATPase and liver specific lipoprotein. The parameters achieved so far allow to use the assay as an undemanding complementary laboratory technique in diagnosing and monitoring hepatopathies of autoimmune origin. Cross reactivity between individual antigen complexes was recorded in the majority of sera from positively reacting patients.

Vitamin D depletion retards the normal regeneration process after partial hepatectomy in the rat.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the hormone of the vitamin D3 (D3) endocrine system, has been shown to influence malignant and normal cell proliferation/differentiation, while insulin (I) is known to be essential for liver growth. To investigate the influence of D3 on liver regeneration, the effect of the D status was studied in D-depleted rats (D-) pretreated with: G1, placebo (D-, hypocalcemic); G2, oral calcium only (D-, normocalcemic); G3, D3; and G4, 1,25-(OH)2D3. Two thirds hepatectomy (HX) or sham operation was performed, and regeneration was studied for 3 weeks.

[Serum lysozyme and copper levels in rats after the administration of dust].

Changes in the content of lysozyme and copper were studied in the blood serum of rats in four time intervals (1, 2, 12, and 24 weeks) after administration of 50 mg TiO2, Sio2 or coal dust and the copper content was also studied 12 weeks after administration of 3 industrial dusts. The obtained results were supplemented by histopathological examinations and in the 12-week interval by the determination of the lung wet weight. The lysozyme content was statistically significantly increased compared to controls practically over the whole time course with differences in the level of the response to SiO2 in comparison with the response to TiO2 and coal.