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Molecular Nutrition & Food Research Jun 2024Organisms maintain their cellular homeostatic balance by interacting with their environment through the use of their cell surface receptors. Membrane based receptors... (Review)
Review
Organisms maintain their cellular homeostatic balance by interacting with their environment through the use of their cell surface receptors. Membrane based receptors such as the transforming growth factor β receptor (TGFR), the prolactin receptor (PRLR), and hepatocyte growth factor receptor (HGFR), along with their associated signaling cascade, play significant roles in retaining cellular homeostasis. While these receptors and related signaling pathways are essential for health of cell and organism, their dysregulation can lead to imbalance in cell function with severe pathological conditions such as cell death or cancer. Ochratoxin A (OTA) can disrupt cellular homeostasis by altering expression levels of these receptors and/or receptor-associated intracellular downstream signaling modulators and/or pattern and levels of their phosphorylation/dephosphorylation. Recent studies have shown that the activity of the TGFR, the PRLR, and HGFR and their associated signaling cascades change upon OTA exposure. A critical evaluation of these findings suggests that while increased activity of the HGFR and TGFR signaling pathways leads to an increase in cell survival and fibrosis, decreased activity of the PRLR signaling pathway leads to tissue damage. This review explores the roles of these receptors in OTA-related pathologies and effects on cellular homeostasis.
PubMed: 38880772
DOI: 10.1002/mnfr.202300777 -
Journal of Animal Physiology and Animal... Jun 2024Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the...
Effects of dietary supplementation with benthic diatom Amphora coffeaeformis on blood biochemistry, steroid hormone levels and seed production efficiency of Nile tilapia Oreochromis niloticus broodstock.
Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the impact of incorporating the benthic diatom Amphora coffeaeformis into the diet of Nile tilapia (Oreochromis niloticus) broodstock, on the blood biochemistry, steroid hormone (SH) levels and seed production efficiency. Broodstock females displaying mature ovary indications were initially combined with males at a ratio of three females to one male. A total of 384 adult Nile tilapia (288 females and 96 males) were used, with 32 fish (24 females and eight males) assigned to each of 12 concrete tanks (8 m³; 2 m × 4 m × 1 m), with three replicate tanks for each dietary treatment, throughout a 14-day spawning cycle until egg harvest. Fish were fed one of four different dietary treatments: AM (control diet), and AM, AM and AM enriched with the diatom A. coffeaeformis at levels of 20, 40 and 60 g/kg of diet respectively. At the trial's conclusion, total protein, albumin, triglyceride and creatinine), SHs (follicle-stimulating hormone, luteinizing hormone, free testosterone, total testosterone, progesterone and prolactin) and seeds production efficiency of Nile tilapia improved significantly (p < 0.05) in alignment with the increment of A. coffeaeformis supplementation. The findings propose that including A. coffeaeformis at levels ranging from 4% to 6% could be effectively employed as a feed additive during the Nile tilapia broodstock's spawning season.
PubMed: 38879794
DOI: 10.1111/jpn.14004 -
Cell Death Discovery Jun 2024As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory...
As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory dysfunction and oocyte aneuploidy parallel chronological age, but poor reproductive outcomes in women older than 35 years are also attributed to endometrial senescence. The current studies, using primary human endometrial stromal cell (ESC) cultures as an in vitro model for endometrial aging, characterize the proinflammatory cytokine, IL-1β-mediated and passage number-dependent effects on ESC phenotype. ESC senescence was accelerated by incubation with IL-1β, which was monitored by RNA sequencing, ELISA, immunocytochemistry and Western blotting. Senescence associated secreted phenotype (SASP) proteins, IL-1β, IL-6, IL-8, TNF-α, MMP3, CCL2, CCL5, and other senescence-associated biomarkers of DNA damage (p16, p21, HMGB1, phospho-γ-histone 2 A.X) were noted to increase directly in response to 0.1 nM IL-1β stimulation. Production of the corresponding SASP proteins increased further following extended cell passage. Using enzyme inhibitors and siRNA interference, these effects of IL-1β were found to be mediated via the c-Jun N-terminal kinase (JNK) signaling pathway. Hormone-induced ESC decidualization, classical morphological and biochemical endocrine responses to estradiol, progesterone and cAMP stimulation (prolactin, IGFBP-1, IL-11 and VEGF), were attenuated pari passu with prolonged ESC passaging. The kinetics of differentiation responses varied in a biomarker-specific manner, with IGFBP-1 and VEGF secretion showing the largest and smallest reductions, with respect to cell passage number. ESC hormone responsiveness was most robust when limited to the first six cell passages. Hence, investigation of ESC cultures as a decidualization model should respect this limitation of cell aging. The results support the hypotheses that "inflammaging" contributes to endometrial senescence, disruption of decidualization and impairment of fecundity. IL-1β and the JNK signaling pathway are pathogenetic targets amenable to pharmacological correction or mitigation with the potential to reduce endometrial stromal senescence and enhance uterine receptivity.
PubMed: 38879630
DOI: 10.1038/s41420-024-02048-6 -
International Journal of Surgery Case... Jul 2024Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine...
INTRODUCTION AND IMPORTANCE
Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine tumor apoplexy were reported in the literature.
CASE PRESENTATION
We report the case of a 45-year-old woman with a history of amenorrhea, and headaches. Neuroimaging showed a very aggressive giant mass within the clivus with the invasion of the sphenoidal sinus and encasement of internal carotid arteries with an empty sella. Endocrinology work-up revealed an exceedingly high level of prolactin surprisingly without galactorrhea. Immunohistochemical analysis after an endonasal biopsy confirmed the diagnosis of prolactinoma. One month after Cabergoline initiation, an apoplexy of the ectopic pituitary neuroendocrine tumor occurred. Conservational management with a decrease in cabergoline dose was performed.
DISCUSSION
This article highlights data from various cases reported in the literature in addition to our case to confirm the extreme rarity of apoplexy as a complication of EPNET.
CONCLUSION
Pituitary apoplexy in ectopic pituitary neuroendocrine tumor is extremely rare. Therefore, in case of unusual localization of pituitary neuroendocrine tumor, a thorough follow-up is necessary to detect complications and ensure early management.
PubMed: 38878728
DOI: 10.1016/j.ijscr.2024.109874 -
Neuropharmacology Jun 2024Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for...
Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for therapeutic purposes. Accordingly, navacaprant (NMRA-140) is a potent, selective KOR antagonist being evaluated as a treatment for major depressive disorder. In the present report, we have extended the pharmacological characterization of navacaprant by further demonstrating its selective KOR antagonist properties and confirming its lack of agonist activity at KORs and related targets involved in opioid-related abuse. Using CHO-K1 cells expressing human KOR, mu (MOR), or delta (DOR) opioid receptors, navacaprant demonstrated selective antagonist properties at KOR (IC = 0.029 μM) versus MOR (IC = 3.3 μM) and DOR (IC > 10 μM) in vitro. In vivo, navacaprant (10-30 mg/kg, i.p.) dose-dependently abolished KOR-agonist induced analgesia in the mouse tail-flick assay. Additionally, navacaprant (10, 30 mg/kg, p.o.) significantly reduced KOR agonist-stimulated prolactin release in mice and rats, confirming KOR antagonism in vivo. Navacaprant showed no agonist activity at any opioid receptor subtype (EC > 10 μM) in vitro and exhibited no analgesic effect in the tail-flick assays at doses ≤100 mg/kg, p.o. thereby confirming a lack of opioid receptor agonist activity in vivo. Importantly, navacaprant did not alter extracellular dopamine concentrations in the nucleus accumbens shell of freely-moving rats following doses ≤100 mg/kg, p.o., whereas morphine (10, 20 mg/kg, i.p.) significantly increased dopamine levels. These results demonstrate that navacaprant is a KOR-selective antagonist with no pharmacological properties implicated in opioid-related abuse.
PubMed: 38876309
DOI: 10.1016/j.neuropharm.2024.110037 -
Journal of the Science of Food and... Jun 2024Prunella vulgaris L., a medicinal and edible homologous plant, is often used to treat conditions such as breast hyperplasia, thyroid enlargement and lymphatic...
The anti-hyperplasia effect of polysaccharide from Prunella vulgaris L. on mammary gland hyperplasia in rats through regulation of the AKT-FOXO3a signaling pathway and intestinal flora.
BACKGROUND
Prunella vulgaris L., a medicinal and edible homologous plant, is often used to treat conditions such as breast hyperplasia, thyroid enlargement and lymphatic tuberculosis. Research has demonstrated that it is particularly effective in the treatment of mammary gland hyperplasia (MGH). However, the material basis and mechanism of its efficacy are still unclear.
RESULTS
Our results showed that in rats with MGH, polysaccharide from Prunella vulgaris L. (PVP) led to a reduction in the levels of estradiol, prolactin and malondialdehyde, while simultaneously increasing the concentrations of progesterone (P), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD) and catalase (CAT) in the serum. In addition, results obtained from 16S rRNA sequencing demonstrated that PVP had the capacity to increase the richness and diversity of the intestinal microbiota in MGH rats, as well as modify the structure of the microbiota. Correlation analysis revealed that the levels of P, SOD, MnSOD and CAT were positively associated with Allobaculum, Romboutsia, Faecalibaculum and Clostridium, while negatively correlated with Turicibacter.
CONCLUSIONS
The mechanism of PVP in treating MGH might be through inhibiting the phosphorylation of the AKT-FOXO3a signaling pathway and then activating the expression of downstream antioxidant enzymes, such as MnSOD and CAT. At the same time, PVP could restore intestinal flora homeostasis in rats with MGH by regulating the flora changes of Allobaculum, Romboutsia, Clostridium and Faecalibaculum, thereby reducing oxidative stress in rats with MGH. © 2024 Society of Chemical Industry.
PubMed: 38872513
DOI: 10.1002/jsfa.13652