Conserved insulin signaling in the regulation of oocyte growth,development, and maturation

Insulin signaling regulates various aspects of physiology, such as glucose homeostasis and aging, and is a key determinant of female reproduction in metazoans. That insulin signaling is crucial for female reproductive health is clear from clinical data linking hyperinsulinemic and hypoinsulinemic condition with certain types of ovarian dysfunction, such as altered steroidogenesis, polycystic ovary syndrome, and infertility. Thus, understanding the signaling mechanisms that underlie the control of insulin‐mediated ovarian development is important for the accurate diagnosis of and intervention for female infertility. Studies of invertebrate and vertebrate model systems have revealed the molecular determinants that transduce insulin signaling as well as which biological processes are regulated by the insulin‐signaling pathway. The molecular determinants of the insulin‐signaling pathway, from the insulin receptor to its downstream signaling components, are structurally and functionally conserved across evolution, from worms to mammals—yet, physiological differences in signaling still exist. Insulin signaling acts cooperatively with gonadotropins in mammals and lower vertebrates to mediate various aspects of ovarian development, mainly owing to evolution of the endocrine system in vertebrates. In contrast, insulin signaling in Drosophila and Caenorhabditis elegans directly regulates oocyte growth and maturation. In this review, we compare and contrast insulin‐mediated regulation of ovarian functions in mammals, lower vertebrates, C. elegans, and Drosophila, and highlight conserved signaling pathways and regulatory mechanisms in general while illustrating insulin's unique role in specific reproductive processes.     

Endometritis Increases Pro-inflammatory Cytokines in Follicular Fluid and Cervico-vaginal Mucus in the Buffalo Cow

Emerging evidence shows that some of the pro-inflammatory cytokines are elevated not only in the endometrium but also in the follicular fluid of cows with endometritis. Developing a cervico-vaginal mucus (CVM) based test has the potential for becoming a pen-side test because of the ease of sample collection. The present study describes the results of two different experiments. The first experiment was conducted to investigate the influence of endometritis on the proinflammatory cytokines of follicular fluid based on the reproductive tracts of buffalo collected at a slaughter house Buffalo genitalia were categorized into purulent endometritis (PE), cytological endometritis (CE), and non-endometritis (NE) based on the white-side test and endometrial cytology, respectively (n?=?14/group). Each group was subdivided into follicular and mid-luteal stage (n?=?7/stage) and the follicular fluid was collected from the largest follicle. Second experiment was done to study the difference in the levels of proinflammatory cytokines in the CVM of repeat breeders with subclinical endometritis presented to the clinic. CVM was collected from the repeaters (n?=?10) and non-repeaters (n?=?10) through aseptic trans-vaginal aspiration. The pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and TNFα were quantitated through bovine specific ELISA kits. Significantly higher concentrations of pro-inflammatory cytokines (IL-1β, IL-8, IL-6, and TNFα) along with low intra-follicular estradiol in buffaloes of PE and CE groups suggest that endometritis impedes the follicular steroidogenesis. Significantly higher concentration of IL-1β and TNF-α in the CVM of repeaters indicate their potential as a pen-side diagnostic test for CE.     

Attenuation of doxorubicin-induced cardiotoxicity and genotoxicity by an indole-based natural compound 3,3′-diindolylmethane (DIM) through activation of Nrf2/ARE signaling pathways and inhibiting apoptosis

The most crucial complication related to doxorubicin (DOX) therapy is nonspecific cytotoxic effect on healthy normal cells. The clinical use of this broad-spectrum chemotherapeutic agent is restricted due to development of severe form of cardiotoxicity, myelosuppression, and genotoxicity which interfere with therapeutic schedule, compromise treatment outcome and may lead to secondary malignancy. 3,3′-diindolylmethane (DIM) is a naturally occurring plant alkaloid formed by the hydrolysis of indolylmethyl glucosinolate (glucobrassicin). Therefore, the present study was undertaken to investigate the protective role of DIM against DOX-induced toxicity in mice. DOX was administered (5?mg/kg b.w., i.p.) and DIM was administered (25?mg/kg b.w., p.o.) in concomitant and 15 days pretreatment schedule. Results showed that DIM significantly attenuated DOX-induced oxidative stress in the cardiac tissues by reducing the levels of free radicals and lipid peroxidation, and by enhancing the level of glutathione (reduced) and the activity of antioxidant enzymes. The chemoprotective potential of DIM was confirmed by histopathological evaluation of heart and bone marrow niche. Moreover, DIM considerably mitigated DOX-induced clastogenicity, DNA damage, apoptosis, and myeloid hyperplasia in bone marrow niche. In addition, oral administration of DIM significantly (p?相似文献   

Cu(II) complexes with square pyramidal (N2S)CuCl2 chromophore: Jahn-Teller distortion and subsequent effect on spectral and structural properties

One monomeric neutral Cu(II) complex [(pmtpm)CuCl₂] (1) is reported by Lindoy and Livingstone [8]. Two new complexes namely, μ-Cl bridged binuclear Cu(II) complex [{(pmtpm)Cu(Cl)}₂ μ-Cl](ClO₄) (2) and a bis μ-Cl bridged binuclear Cu(II) complex [{(pmtpm)Cu}₂(μ-Cl)₂](ClO₄)₂ (3) derived from a tridentate Schiff base ligand, 2-pyridyl-N-(2′-methylthiophenyl)methyleneimine (pmtpm) were synthesized and characterized by various spectroscopic methods and by X-ray crystallography. (N₂S)CuCl₂ chromophore(s) of distorted square pyramidal coordination geometries around Cu(II) ion(s) have been observed for all the complexes 1-3. The equatorial sites of the square plane comprise two N and a thioether S donor atoms of the pmtpm ligand as well as one Cl⁻ ion (terminal in 1 and 2, and bridging in 3) while the remaining axial site is occupied by a terminal Cl⁻ ion (for 1) or a bridging Cl⁻ ion (for 2 and 3). The equatorial Cu-Cl distances are much shorter [1: 2.2511(4) Å, 2: 2.2307(12) Å, 3: 2.2513(12) Å] than the axial Cu-Cl distances [1: 2.4394(4) Å, 2: 2.5597(9) Å, 3: 2.7037(12) Å]. The correlation of an axial Cu-Cl bond elongation with a lower g_|| value in the solid state EPR spectrum and a blue shifted ligand field transition in the solid and solution phase absorption spectrum has been observed.     

Characterization of <Emphasis Type="Italic">p</Emphasis>-hydroxybenzaldehyde dehydrogenase,the final enzyme of <Emphasis Type="Italic">p</Emphasis>-hydroxybenzoic acid biosynthesis in hairy roots of <Emphasis Type="Italic">Daucus carota</Emphasis>

Hairy root cultures of Daucus carota respond to methyl-jasmonate treatment with enhanced accumulation of p-hydroxybenzoic acid. The final C₁-side chain of this compound is shaped by p-hydroxybenzaldehyde dehydrogenase (HBD) that catalyzes the formation of p-hydroxybenzoic acid from p-hydroxybenzaldehyde in the presence of NAD⁺. HBD was biochemically characterized from cell-free hairy root extracts of D. carota. The preferred substrate for HBD was p-hydroxybenzaldehyde. The apparent K _m values were 54.8 and 74.4 μM for p-hydroxybenzaldehyde and NAD⁺, respectively. Divalent metal cations did not significantly affect enzyme activity.     

Site-1 protease is essential to growth plate maintenance and is a critical regulator of chondrocyte hypertrophic differentiation in postnatal mice

Site-1 protease (S1P) is a proprotein convertase with essential functions in lipid homeostasis and unfolded protein response pathways. We previously studied a mouse model of cartilage-specific knock-out of S1P in chondroprogenitor cells. These mice exhibited a defective cartilage matrix devoid of type II collagen protein (Col II) and displayed chondrodysplasia with no endochondral bone formation even though the molecular program for endochondral bone development appeared intact. To gain insights into S1P function, we generated and studied a mouse model in which S1P is ablated in postnatal chondrocytes. Postnatal ablation of S1P results in chondrodysplasia. However, unlike early embryonic ablations, the growth plates of these mice exhibit a lack of Ihh, PTHrP-R, and Col10 expression indicating a loss of chondrocyte hypertrophic differentiation and thus disruption of the molecular program required for endochondral bone development. S1P ablation results in rapid growth plate disruption due to intracellular Col II entrapment concomitant with loss of chondrocyte hypertrophy suggesting that these two processes are related. Entrapment of Col II in the chondrocytes of the prospective secondary ossification center precludes its development. Trabecular bone formation is dramatically diminished in the primary spongiosa and is eventually lost. The primary growth plate is eradicated by apoptosis but is gradually replaced by a fully functional new growth plate from progenitor stem cells capable of supporting new bone growth. Our study thus demonstrates that S1P has fundamental roles in the preservation of postnatal growth plate through chondrocyte differentiation and Col II deposition and functions to couple growth plate maturation to trabecular bone development in growing mice.     

Effects of aging on growth factors gene and protein expression in the dorsal and ventral lobes of rat prostate

We hypothesize that various growth factors and their receptors gene and protein are modulated in dorsal and ventral lobes of aging prostate. To test this hypothesis, TGFbeta1, TGFbeta2 TGFbeta3, TGFbetaR-I, TGFbetaR-II, TGFalpha, EGF, EGFR, KGF and KGFR gene and protein expression were analyzed in dorsal and ventral lobes of aging rat prostates (1, 3, 6, 9, 12, 18, 24, and 28/30 months). KGF gene expression was very weak or absent in 1, 3, and 6 month old rat dorsal and ventral lobes of prostate whereas it re-expressed in 9, 12, 18, 24 and 30 month old rat prostate. All growth factors and their receptors expect KGF and EGFR were mainly localized in epithelium of ventral and dorsal lobes of aging rat prostates. EGF, TGFalpha, TGFbeta1, and TGFbetaR-I protein expression was lacking in stroma of dorsal and ventral lobes of 1, 3, 6, 9, 12/18 months old rat prostates. However, EGF, TGFbeta1 and TGFbetaR-I proteins re-expressed in stroma of 24 and 28 months old rat prostates. KGF protein expression was lacking in epithelium of dorsal and ventral lobes of all aging rat prostates. This is the first report to demonstrate differential gene and protein expression of growth factors in dorsal and ventral lobes is associated with aging rat prostate, suggesting their role in pathogenesis of prostatic diseases with aging.     

Survival,prophage induction,and invasive properties of lysogenic Salmonella Typhimurium exposed to simulated gastrointestinal conditions

This study was designed to evaluate the viability, prophage induction, invasive ability, and relative gene expression in lysogenic Salmonella Typhimurium exposed to the simulated gastric juice (SGJ) at pH 2 (SGJ-2), 3 (SGJ-3), 4 (SGJ-4), and 5 (SGJ-5) for 30 min followed by 0.5 % bile salts for 2 h. The susceptibility of lysogenic S. Typhimurium increased with decreasing pH value and increasing bile salt concentration. The lysogenic S. Typhimurium cells were least susceptible to SGJ-4 and SGJ-5, showing <1 log reduction. The highest prophage induction was observed by 3.34 log PFU/ml in lysogenic S. Typhimurium at SGJ-3 in the presence of 0.5 % bile salts. The numbers of invading lysogenic S. Typhimurium treated at SGJ-3, SGJ-4, and SGJ-5 were 3.57, 3.73, and 4.15 log CFU/cm², respectively. Most genes (hilA, hilC, hilD, invA, invE, invF, and sirA) were down-regulated in lysogenic S. Typhimurium treated at SGJ-3, SGJ-4, and SGJ-5. This study provides useful information for understanding physiological changes of lysogenic S. Typhimurium in the simulated gastrointestinal conditions.