Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse ...development then, in the spontaneously type 2 diabetes models associated with infertility db/db and ob/ob mice. IR-β and α were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum.
Serum and tissue glucose were measured with enzymatic colorimetric assays and InsulinT and Insulin2 by ELISAs in serum, interstitial tissue- (ITf) and seminiferous tubule (STf) fractions in14- > 60-day-old normal and db/db, ob/ob and wild type (WT) mice. IR subunits were assessed by immunoblotting in tissues and by immunoprecipitation followed by immunoblotting in serum.
Development: Glucose increased in serum, ITf and STf. InsulinT and Insulin2 dropped in serum; both were higher in STf than in ITf. In > 60-day-old mouse ITf, insulinT rose whereas Insulin2 decreased; InsulinT and Insulin2 rose concurrently in STf. Glucose and insulin were high in > 60-day-old ITf; in STf high insulin2 accompanied low glucose. One hundred ten kDa IR-β peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-α was high in ITf but decreased in STf. Glucose escalated in db/db and ob/ob sera. Glucose doubled in ITf while being halved in STf in db/db mice. Glucose significantly dropped in db/db and ob/ob mice spermatozoa. InsulinT and Insulin2 rose significantly in the serum, ITf and STf in db/db and ob/ob mice. One hundred ten kDa IR-β and 135 kDa IR-α decreased in db/db and ob/ob ITf. Only 110 kDa IR-β dropped in db/db and ob/ob STf and AP. One hundred ten kDa IR-β fell in db/db and ob/ob SPZ. One hundred ten kDa sIR-α rose in the db/db and ob/ob mouse sera.
Insulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-β and 135 kDa IR-α in the db/db and ob/ob interstitial tissue suggest a loss of active receptor sites that could alter the testicular cell insulin binding and response to the hormone. Decreased IR-β levels were insufficient to stimulate downstream effectors in AP and tubules. IR-α shedding increased in db/db and ob/ob mice.
In this work, the effects of light quality and beneficial microbes (biofertilizer) supply on structural and ecophysiological traits of spinach were investigated. Plants were grown under four light ...quality regimens: white light (WL), red-blue (RB), red-green (RG), and red (R) light, with or without the addition of biofertilizer. RG and R plants without biofertilizer showed morphological traits typical of shaded plants as wide leaf lamina and high photosynthetic pigment content. These plants also exhibited a higher photosynthetic capacity compared to WL and RB plants. The improved photosynthesis in RG plants was due to both morphological and physiological adjustments allowing a better utilisation of light energy, whereas in R plants it has been attributed to a reduced photorespiration rate. Biofertilizer application under WL improved plant performance enhancing photosynthesis. The high carbon gain compensates the costs of symbiosis. Biofertilizer application under R light favouring too much the microbial root colonisation, removed the benefits of symbiosis. The interaction of light quality and biofertilization significantly affects the root-microbe relationship.
Hyaluronan (HA) has gained significant attention in cancer research for its role in modulating chemoresistance. This review aims to elucidate the mechanisms by which HA contributes to ...chemoresistance, focusing on its interactions within the tumor microenvironment. HA is abundantly present in the extracellular matrix (ECM) and binds to cell-surface receptors such as CD44 and RHAMM. These interactions activate various signaling pathways, including PI3K/Akt, MAPK, and NF-κB, which are implicated in cell survival, proliferation, and drug resistance. HA also influences the physical properties of the tumor stroma, enhancing its density and reducing drug penetration. Additionally, HA-mediated signaling contributes to the epithelial–mesenchymal transition (EMT), a process associated with increased metastatic potential and resistance to apoptosis. Emerging therapeutic strategies aim to counteract HA-induced chemoresistance by targeting HA synthesis, degradation, metabolism, or its binding to CD44. This review underscores the complexity of HA’s role in chemoresistance and highlights the potential for HA-targeted therapies to improve the efficacy of conventional chemotherapeutics.
The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor ...cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.
In antineoplastic therapy, one of the challenges is to adjust the treatment to the needs of each patient and reduce the toxicity caused by conventional antitumor strategies. It has been demonstrated ...that natural products with antitumoral properties are less toxic than chemotherapy and radiotherapy. Also, using already developed drugs allows developing substantially less costly methods for the discovery of new treatments than traditional drug development. Candidate molecules proposed for drug repositioning include 4-methylumbelliferone (4-MU), an orally available dietetic product, derivative of coumarin and mainly found in the plant family Umbelliferae or Apiaceae. 4-MU specifically inhibits the synthesis of glycosaminoglycan hyaluronan (HA), which is its main mechanism of action. This agent reduces the availability of HA substrates and inhibits the activity of different HA synthases. However, an effect independent of HA synthesis has also been observed. 4-MU acts as an inhibitor of tumor growth in different types of cancer. Particularly, 4-MU acts on the proliferation, migration and invasion abilities of tumor cells and inhibits the progression of cancer stem cells and the development of drug resistance. In addition, the effect of 4-MU impacts not only on tumor cells, but also on other components of the tumor microenvironment. Specifically, 4-MU can potentially act on immune, fibroblast and endothelial cells, and pro-tumor processes such as angiogenesis. Most of these effects are consistent with the altered functions of HA during tumor progression and can be interrupted by the action of 4-MU. While the potential advantage of 4-MU as an adjunct in cancer therapy could improve therapeutic efficacy and reduce toxicities of other antitumoral agents, the greatest challenge is the lack of scientific evidence to support its approval. Therefore, crucial human clinical studies have yet to be done to respond to this need. Here, we discuss and review the possible applications of 4-MU as an adjunct in conventional antineoplastic therapies, to achieve greater therapeutic success. We also describe the main proposed mechanisms of action that promote an increase in the efficacy of conventional antineoplastic strategies in different types of cancer and prospects that promote 4-MU repositioning and application in cancer therapy.
Rising daily temperatures and water shortage are two of the major concerns in agriculture.
In this work, we analysed the tolerance traits in a tomato line carrying a small region of the Solanum ...pennellii wild genome (IL12‐4‐SL) when grown under prolonged conditions of single and combined high temperature and water stress.
When exposed to stress, IL12‐4‐SL showed higher heat tolerance than the cultivated line M82 at morphological, physiological, and biochemical levels. Moreover, under stress IL12‐4‐SL produced more flowers than M82, also characterized by higher pollen viability. In both lines, water stress negatively affected photosynthesis more than heat alone, whereas the combined stress did not further exacerbate the negative impacts of drought on this trait. Despite an observed decrease in carbon fixation, the quantum yield of PSII linear electron transport in IL12‐4‐SL was not affected by stress, thereby indicating that photochemical processes other than CO2 fixation acted to maintain the electron chain in oxidized state and prevent photodamage. The ability of IL12‐4‐SL to tolerate abiotic stress was also related to the intrinsic ability of this line to accumulate ascorbic acid.
The data collected in this study clearly indicate improved tolerance to single and combined abiotic stress for IL12‐4‐SL, making this line a promising one for cultivation in a climate scenario characterized by frequent and long‐lasting heatwaves and low rainfall.
IL 12‐4‐SL is a promising tomato line to address the major challenges associated with climate change.
This work aimed to evaluate if chilling stress may be mitigated by elevated CO
2
(EC) in
Beta vulgaris
L. plants. Photosynthetic rate was measured at 21% and 2% O
2
after a short-term exposure of 5 h ...at four different treatments: 360 μmol(CO
2
) mol
–1
/25°C (AC); 360 μmol(CO
2
) mol
–1
/4°C (AC+LT); 700 μmol(CO
2
) mol
–1
/25°C (EC); 700 μmol(CO
2
) mol–1/4°C (EC+LT). Compared to AC+LT, EC+LT plants showed higher values of CO
2
fixation, photochemical activity, and Rubisco amount. These latter invest a higher portion of photosynthetic electron flow to O
2
, differently from AC+LT plants that promote the regulated thermal dissipation processes. In EC+LT plants, the photosynthetic electron flow to O
2
acts as a safety mechanism against the excess of absorbed light, upon return to prechilling conditions, allowing photosynthetic apparatus to maintain its efficiency. In AC+LT plants, the increase of thermal dissipation processes was not adequate to guarantee the PSII photoprotection and the photosynthetic recovery after chilling.
Recent studies of plant-animal mutualistic networks have assumed that interaction frequency between mutualists predicts species impacts (population-level effects), and that field estimates of ...interaction strength (per-interaction effects) are unnecessary. Although existing evidence supports this assumption for the effect of animals on plants, no studies have evaluated it for the reciprocal effect of plants on animals. We evaluate this assumption using data on the reproductive effects of pollinators on plants and the reciprocal reproductive effects of plants on pollinators. The magnitude of species impacts of plants on pollinators, the reciprocal impacts of pollinators on plants, and their asymmetry were well predicted by interaction frequency. However, interaction strength was a key determinant of the sign of species impacts. These results underscore the importance of quantifying interaction strength in studies of mutualistic networks. We also show that the distributions of interaction strengths and species impacts are highly skewed, with few strong and many weak interactions. This skewed distribution matches the pattern observed in food webs, suggesting that the community-wide organization of species interactions is fundamentally similar between mutualistic and antagonistic interactions. Our results have profound ecological implications, given the key role of interaction strength for community stability.
Basic fibroblast growth factor (bFGF) is a mitogenic and differentiating cytokine. In the anterior pituitary, folliculostellate (FS) cells constitute the major source of bFGF. bFGF affects endocrine ...cell proliferation and secretion in the anterior pituitary. In addition, bFGF increases its own expression by acting directly on FS cells. FS cell Cx43‐mediated gap junction intercellular communication allows the establishment of an intrapituitary network for the transmission of information. In the present study, we assessed how bFGF regulates FS cell coupling. Time course studies were carried out on the FS cell line TtT/GF. Short‐term bFGF treatment induced a transient cell uncoupling and the phosphorylation in Ser368 of membrane‐bound Cx43 without modifying Cx43 levels. We demonstrated the involvement of the protein kinase C (PKC) isoform α in the phosphorylation of Cx43 in S368. Moreover, we showed that bFGF induced PKCα activation by stimulating its expression, phosphorylation and association with the plasma membrane. The long‐term incubation with bFGF increased TtT/GF cell coupling, total Cx43 levels and Cx43 accumulation at the cell membrane of cytoplasmic projections. The Cx43 level increase was a result of the stimulation of Cx43 gene transcription as mediated by the extracellular‐regulated kinase 1/2 signalling pathway. Taken together, the data show that bFGF modulates TtT/GF cell coupling by activating different pathways that lead to opposite effects on Cx43 phosphorylation and expression depending on the duration of the exposure of the cells to bFGF. A short‐term bFGF exposure reduces cell‐to‐cell communication as a mean of desynchronising FS cells. By contrast, long‐term exposure to bFGF enhances cell‐to‐cell communication and facilitates coordination among FS cells.
Gap junction-mediated communication helps synchronize interconnected Sertoli cell activities. Besides, coordination of germ cell and Sertoli cell activities depends on gap junction-mediated Sertoli ...cell-germ cell communication. This report assesses mechanisms underlying the regulation of connexin 46 (Cx46) and Cx50 in mouse testis and those accompanying a "natural" seasonal and a pathological arrest of spermatogenesis, resulting from autoimmune orchitis (AIO) in mink. Furthermore, the impact of deleting Cx46 or Cx50 on the expression, phosphorylation of junction proteins, and spermatogenesis is evaluated. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. During the mink active spermatogenic phase, Cx50 became phosphorylated and localized to the site of the blood-testis barrier. By contrast, Cx46 was dephosphorylated and associated with annular junctions, suggesting phosphorylation/dephosphorylation of Cx46 and Cx50 involvement in the barrier dynamics. Cx46-positive annular junctions in contact with lipid droplets were found. Cx46 and Cx50 expression and localization were altered in mink with AIO. The deletion of Cx46 or Cx50 impacted on other connexin expression and phosphorylation and differently affected tight and adhering junction protein expression. The level of apoptosis, determined by ELISA, and a number of Apostain-labeled spermatocytes and spermatids/tubules were higher in mice lacking Cx46 (Cx46-/-) than wild-type and Cx50-/- mice, arguing for life-sustaining Cx46 gap junction-mediated exchanges in late-stage germ cells secluded from the blood by the barrier. The data show that expression and phosphorylation of Cx46 and Cx50 are complementary in seminiferous tubules.