Enhancing drought, heat shock, and combined stress tolerance in Myrobalan 29C rootstocks with foliar application of potassium nitrate.

BACKGROUND: Drought and heat stress are significant concerns to food security in arid and semi-arid regions, where global warming is predicted to increase both frequency and severity. To cope with these challenges, the use of drought-tolerant plants or technological interventions are essential. In this study, the effects of foliar potassium nitrate (KNO3) application on the stress tolerance and recovery of Myrobalan 29C rootstocks (Prunus cerasifera Ehrh.) were evaluated. These rootstocks are widely recognized for their adaptability and are extensively used in fruit production. To assess their response, the rootstocks were subjected to drought, heat shock, or a combination of both stressors. Additionally, they were treated with 1.0% KNO3 via foliar application. Throughout the stress and recovery periods, various morphological, physiological, and bio-chemical parameters were measured. RESULTS: Based on our results, KNO3 treatment improved LRWC, Chl stability, SC, and key stress markers like proline, MDA, H2O2, along with antioxidant enzymes CAT, SOD, POD during both stress and recovery phases. Moreover, our results emphasized KNO3's critical role in hormone regulation under stress. KNO3 application significantly altered hormone levels, notably increasing ABA during drought and heat shock stress, essential for stress response and adaptation. In contrast, IAA, GA, and cytokinin's significantly increased during the recovery phase in KNO3-treated plants, indicating improved growth regulation and stress recovery. In addition, KNO3 application improved the recovery process of the rootstocks by restoring their physiological and biochemical functions. CONCLUSION: This study suggests that the application of foliar KNO3 is an effective technique for enhancing the drought and heat tolerance as well as the recovery of Myrobalan 29C rootstocks. These results hold significant value for farmers, policymakers, and researchers, as they offer crucial insights into the development of drought-tolerant crops and the management of climate change's adverse effects on agriculture.

Prohexadione-calcium improves grape quality by regulating endogenous hormones, sugar and acid metabolism and related enzyme activities in grape berries.

Prohexadione-Calcium (Pro-Ca) plays key roles in improving fruit quality and yield by regulating various aspects of plant growth. However, the effects of how Pro-Ca regulates the regulation of sugar and acid balance and its impact on the production of volatile aroma substances during fruit growth and development are poorly understood. In this study, the Pro-Ca solutions developed at concentrations of 200, 400, 600 and 800 mg·L-1 were sprayed on the entire "Chardonnay" grape tree 22, 42, 62 and 82 days after initial flowering. The values of endogenous hormones, sugar and acid content, enzyme activities and flavor content were then measured in grapes 45, 65, 85 and 105 days (ripeness stage) after the initial flowering. The results showed that Pro-Ca had significant effects on fruits during development, including reducing ABA content, increasing ZT, GA3 and IAA levels, promoting fruit ripening and enhancing enzymes, which are involved in sugar and acid synthesis. Consequently, these effects led to an increase in sugar and acid content in the berries. Particularly during the ripening phase, the application of 600 mg L-1 Pro-Ca resulted in an increase in soluble sugar content of 11.28% and a significant increase in citric acid and malic acid content of 97.80% and 68.86%, respectively. Additionally, Pro-Ca treatment enhanced both the variety and quantity of aroma compounds present in the berries, with the 600 mg·L-1 Pro-Ca treatment showcasing the most favorable impact on volatile aroma compounds in 'Chardonnay' grapes. The levels of aldehydes, esters, alcohols, phenols, acids, ketones, and terpenes were significantly higher under the 600 mg·L-1 Pro-Ca treatment compared to those of control with 51.46 - 423.85% increase. In conclusion, Pro-Ca can regulate the content of endogenous hormones and the activities of enzymes related to sugar and acid metabolism in fruit, thereby increasing the content of soluble sugar and organic acid in fruit and the diversity and concentration of fruit aroma substances. Among them, foliar spraying 600 mg · L-1 Pro-Ca has the best effect. In the future, we need to further understand the molecular mechanism of Pro-Ca in grape fruit to lay a solid foundation for quality improvement breeding.

Identification of genetics and hormonal factors involved in Quercus robur root growth regulation in different cultivation system.

Understanding the molecular processes and hormonal signals that govern root growth is of paramount importance for effective forest management. While Arabidopsis studies have shed light on the role of the primary root in root system development, the structure of root systems in trees is considerably more intricate, posing challenges to comprehend taproot growth in acorn-sown and nursery-cultivated seedlings. In this study, we investigated Quercus robur seedlings using rhizotrons, containers, and transplanted containers to rhizotrons, aiming to unravel the impact of forest nursery practices on processes governing taproot growth and root system development. Root samples were subjected to RNA-seq analysis to identify gene expression patterns and perform differential gene expression and phytohormone analysis. Among studied cultivation systems, differentially expressed genes (DEGs) exhibited significant diversity, where the number of co-occurring DEGs among cultivation systems was significantly smaller than the number of unique DEGs in different cultivation systems. Moreover, the results imply that container cultivation triggers the activation of several genes associated with linolenic acid and peptide synthesis in root growth. Upon transplantation from containers to rhizotrons, rapid enhancement in gene expression occurs, followed by gradual reduction as root growth progresses, ultimately reaching a similar expression pattern as observed in the taproot of rhizotron-cultivated seedlings. Phytohormone analysis revealed that taproot growth patterns under different cultivation systems are regulated by the interplay between auxin and cytokinin concentrations. Moreover, the diversification of hormone levels within the root zone and cultivation systems allows for taproot growth inhibition and prompt recovery in transplanted seedlings. Our study highlights the crucial role of hormone interactions during the early stages of taproot elongation, influencing root system formation across.

Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration.

The limited endogenous regenerative capacity of the human heart renders cardiovascular diseases a major health threat, thus motivating intense research on in vitro heart cell generation and cell replacement therapies. However, so far, in vitro-generated cardiomyocytes share a rather fetal phenotype, limiting their utility for drug testing and cell-based heart repair. Various strategies to foster cellular maturation provide some success, but fully matured cardiomyocytes are still to be achieved. Today, several hormones are recognized for their effects on cardiomyocyte proliferation, differentiation, and function. Here, we will discuss how the endocrine system impacts cardiomyocyte maturation. After detailing which features characterize a mature phenotype, we will contemplate hormones most promising to induce such a phenotype, the routes of their action, and experimental evidence for their significance in this process. Due to their pleiotropic effects, hormones might be not only valuable to improve in vitro heart cell generation but also beneficial for in vivo heart regeneration. Accordingly, we will also contemplate how the presented hormones might be exploited for hormone-based regenerative therapies.

Effects of different hormonal treatments on spermatogenesis advancement in hatchery-produced greater amberjack Seriola dumerili (Risso 1810).

In earlier studies, wild-caught greater amberjack Seriola dumerili (Risso, 1810) males reared in sea cages showed gametogenesis impairment and low sperm production and quality. Here, we (a) examined if F1 hatchery-produced males reared in sea cages also exhibit reproductive dysfunctions and (b) evaluated the effects of gonadotropin releasing hormone agonist (GnRHa) administration through injections (GnRHainj) or sustained-release implants (GnRHaimpl), and human chorionic gonadotropin (hGC) injections on spermatogenesis/spermiation enhancement. Fish were given a hormone treatment just prior to the spawning season, and were transferred to land-based tanks, according to an established spawning induction protocol. Blood samples (n = 6) were obtained on Days 0, 7 and 13 after treatment. Testis samples were obtained on Days 0 (n = 4) and 13 (n = 2 per treatment). The fish prior to their transfer from the sea cages to the land-based tanks, exhibited a low gonadosomatic index, altered sex steroid hormone profile and high density of testicular apoptotic cells. After transfer to tanks, there was a general depression of sex steroid plasma levels parallel to an increase in cortisol concentrations. Despite the negative effect on steroidogenesis by the transfer from the sea, the hormonal treatments increased the number of fish from where sperm could be obtained, as well as testis growth, and reduced testicular apoptosis. Treatment with hCG resulted in the most significant changes in spermatogenesis, while GnRHaimpl appeared to induce less intense, but likely longer-lasting effects. The study indicated that F1 hatchery-produced males also exhibited reproductive dysfunctions as wild-caught captive-reared greater amberjack, and that the observed positive effects of the hormone treatments on spermiation/spermatogenesis were likely mediated by factors other than sex steroid hormones.

Glycogen phosphorylase isoenzyme GPbb versus GPmm regulation of ventromedial hypothalamic nucleus glucoregulatory neurotransmitter and counter-regulatory hormone profiles during hypoglycemia: Role of L-lactate and octadecaneuropeptide.

Glucose accesses the brain primarily via the astrocyte cell compartment, where it passes through the glycogen shunt before catabolism to the oxidizable fuel L-lactate. Glycogen phosphorylase (GP) isoenzymes GPbb and GPmm impose distinctive control of ventromedial hypothalamic nucleus (VMN) glucose-regulatory neurotransmission during hypoglycemia, but lactate and/or gliotransmitter involvement in those actions is unknown. Lactate or the octadecaneuropeptide receptor antagonist cyclo(1-8)[DLeu5] OP (LV-1075) did not affect gene product down-regulation caused by GPbb or GPmm siRNA, but suppressed non-targeted GP variant expression in a VMN region-specific manner. Hypoglycemic up-regulation of neuronal nitric oxide synthase was enhanced in rostral and caudal VMN by GPbb knockdown, yet attenuated by GPMM siRNA in the middle VMN; lactate or LV-1075 reversed these silencing effects. Hypoglycemic inhibition of glutamate decarboxylase65/67 was magnified by GPbb (middle and caudal VMN) or GPmm (middle VMN) knockdown, responses that were negated by lactate or LV-1075. GPbb or GPmm siRNA enlarged hypoglycemic VMN glycogen profiles in rostral and middle VMN. Lactate and LV-1075 elicited progressive rostral VMN glycogen augmentation in GPbb knockdown rats, but stepwise-diminution of rostral and middle VMN glycogen after GPmm silencing. GPbb, not GPmm, knockdown caused lactate or LV-1075 - reversible amplification of hypoglycemic hyperglucagonemia and hypercorticosteronemia. Results show that lactate and octadecaneuropeptide exert opposing control of GPbb protein in distinct VMN regions, while the latter stimulates GPmm. During hypoglycemia, GPbb and GPmm may respectively diminish (rostral, caudal VMN) or enhance (middle VMN) nitrergic transmission and each oppose GABAergic signaling (middle VMN) by lactate- and octadecaneuropeptide-dependent mechanisms.

Pesticides exposure and compromised fitness in wild birds: Focusing on the reproductive endocrine disruption.

Exposure of pesticides to wildlife species, especially on the aspect of endocrine disruption is of great concern. Wildlife species are more at risk to harmful exposures to the pesticides in their natural habitat through diet and several other means. Species at a higher tropic level in the food chain are more susceptible to the deleterious effects due to sequential biomagnifications of the pesticides/metabolites. Pesticides directly affect fitness of the species in the wild causing reproductive endocrine disruption impairing the hormones of the gonads and thyroid glands as reproduction is under the influence of cross regulations of these hormones. This review presents a comprehensive compilation of important literatures on the impact of the current use pesticides in disruption of both the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes particularly in birds addressing impacts on the reproductive impairments and overall fitness. In addition to the epidemiological studies, laboratory investigations those provide supportive evidences of the probable mechanisms of disruption in the wild also have been incorporated in this review. To accurately predict the endocrine-disruption of the pesticides as well as to delineate the risk associated with potential cumulative effects, studies are to be more focused on the environmentally realistic exposure dose, mixture pesticide exposures and transgenerational effects. In addition, strategic screening/appropriate methodologies have to be developed to reveal the endocrine disruption potential of the contemporary use pesticides. Demand for adequate quantitative structure-activity relationships and insilico molecular docking studies for timely validation have been highlighted.

Ouabain enhances renal cyst growth in a slowly progressive mouse model of autosomal dominant polycystic kidney disease.

Renal cyst progression in autosomal dominant polycystic kidney disease (ADPKD) is highly dependent on agents circulating in blood. We have previously shown, using different in vitro models, that one of these agents is the hormone ouabain. By binding to Na+-K+-ATPase (NKA), ouabain triggers a cascade of signal transduction events that enhance ADPKD cyst progression by stimulating cell proliferation, fluid secretion, and dedifferentiation of the renal tubular epithelial cells. Here, we determined the effects of ouabain in vivo. We show that daily administration of ouabain to Pkd1RC/RC ADPKD mice for 1-5 mo, at physiological levels, augmented kidney cyst area and number compared with saline-injected controls. Also, ouabain favored renal fibrosis; however, renal function was not significantly altered as determined by blood urea nitrogen levels. Ouabain did not have a sex preferential effect, with male and female mice being affected equally. By contrast, ouabain had no significant effect on wild-type mice. In addition, the actions of ouabain on Pkd1RC/RC mice were exacerbated when another mutation that increased the affinity of NKA for ouabain was introduced to the mice (Pkd1RC/RCNKAα1OS/OS mice). Altogether, this work highlights the role of ouabain as a procystogenic factor in the development of ADPKD in vivo, that the ouabain affinity site on NKA is critical for this effect, and that circulating ouabain is an epigenetic factor that worsens the ADPKD phenotype.NEW & NOTEWORTHY This work shows that the hormone ouabain enhances the progression of autosomal dominant polycystic kidney disease (ADPKD) in vivo. Ouabain augments the size and number of renal cysts, the kidney weight to body weight ratio, and kidney fibrosis in an ADPKD mouse model. The Na+-K+-ATPase affinity for ouabain plays a critical role in these effects. In addition, these outcomes are independent of the sex of the mice.

The interplay of auxin and brassinosteroid signaling tunes root growth under low and different nitrogen forms.

The coordinated signaling activity of auxin and brassinosteroids (BRs) is critical for optimal plant growth and development. Nutrient-derived signals regulate root growth by modulating the levels and spatial distribution of growth hormones to optimize nutrient uptake and assimilation. However, the effect of the interaction of these two hormones and their signaling on root plasticity during low and differential availability of nitrogen (N) forms (NH4+/NO3-) remains elusive. We demonstrate that root elongation under low N (LN) is an outcome of the interdependent activity of auxin and BR signaling pathways in Arabidopsis (Arabidopsis thaliana). LN promotes root elongation by increasing BR-induced auxin transport activity in the roots. Increased nuclear auxin signaling and its transport efficiency have a distinct impact on root elongation under LN conditions. High auxin levels reversibly inhibit BR signaling via BRI1 KINASE INHIBITOR1. Using the tissue-specific approach, we show that BR signaling from root vasculature (stele) tissues is sufficient to promote cell elongation and, hence, root growth under LN condition. Further, we show that N form-defined root growth attenuation or enhancement depends on the fine balance of BR and auxin signaling activity. NH4+ as a sole N source represses BR signaling and response, which in turn inhibits auxin response and transport, whereas NO3- promotes root elongation in a BR signaling-dependent manner. In this study, we demonstrate the interplay of auxin and BR-derived signals, which are critical for root growth in a heterogeneous N environment and appear essential for root N foraging response and adaptation.

Ran-GTP/-GDP-dependent nuclear accumulation of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and TGACG-BINDING FACTOR2 controls salicylic acid-induced leaf senescence.

Leaf senescence is the final stage of leaf development and can be triggered by various external factors, such as hormones and light deprivation. In this study, we demonstrate that the overexpression of the GTP-bound form of Arabidopsis (Arabidopsis thaliana) Ran1 (a Ras-related nuclear small G-protein, AtRan1) efficiently promotes age-dependent and dark-triggered leaf senescence, while Ran-GDP has the opposite effect. Transcriptome analysis comparing AtRan1-GDP- and AtRan1-GTP-overexpressing transgenic plants (Ran1T27Nox and Ran1G22Vox, respectively) revealed that differentially expressed genes (DEGs) related to the senescence-promoting hormones salicylic acid (SA), jasmonic acid, abscisic acid, and ethylene (ET) were significantly upregulated in dark-triggered senescing leaves of Ran1G22Vox, indicating that these hormones are actively involved in Ran-GTP/-GDP-dependent, dark-triggered leaf senescence. Bioinformatic analysis of the promoter regions of DEGs identified diverse consensus motifs, including the bZIP motif, a common binding site for TGACG-BINDING FACTOR (TGA) transcription factors. Interestingly, TGA2 and its interactor, NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1), which are two positive transcriptional regulators of SA signaling, differed in their extent of accumulation in the nucleus versus cytoplasm of Ran1T27Nox and Ran1G22Vox plants. Moreover, SA-induced, Ran-GTP-/-GDP-dependent functions of NPR1 included genome-wide global transcriptional reprogramming of genes involved in cell death, aging, and chloroplast organization. Furthermore, the expression of AtRan1-GTP in SA signaling-defective npr1 and SA biosynthesis-deficient SA-induction deficient2 genetic backgrounds abolished the effects of AtRan1-GTP, thus retarding age-promoted leaf senescence. However, ET-induced leaf senescence was not mediated by Ran machinery-dependent nuclear shuttling of ETHYLENE-INSENSITIVE3 and ETHYLENE-INSENSITIVE3-LIKE1 proteins. We conclude that Ran-GTP/-GDP-dependent nuclear accumulation of NPR1 and TGA2 represents another regulatory node for SA-induced leaf senescence.

Chronic stress in solid tumor development: from mechanisms to interventions.

Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells. Current clinical evidences also suggest that chronic stress affects the outcome of cancer treatment. However, in clinic, there is lack of effective treatment for chronic stress in cancer patients. In this review, we discuss the main mechanisms by which chronic stress regulates the tumor microenvironment, including functional regulation of tumor cells by stress hormones (stem cell-like properties, metastasis, angiogenesis, DNA damage accumulation, and apoptotic resistance), metabolic reprogramming and immune escape, and peritumor neuromodulation. Based on the current clinical treatment framework for cancer and chronic stress, we also summarize pharmacological and non-pharmacological therapeutic approaches to provide some directions for cancer therapy.

A cocktail probe approach to evaluate the effect of hormones on the expression and activity of CYP enzymes in human hepatocytes with conditions simulating late stage of pregnancy.

PURPOSE: Pregnancy-mediated physiological and biochemical changes contribute to alterations in the pharmacokinetics of certain drugs. There is a paucity of data on the systematic evaluation of the underlying mechanisms. The objective of the current study was to examine the impact of changes in circulating and tissue hormonal concentration during the late stage of pregnancy on the activity and expression of hepatic cytochrome P450 (CYP) enzymes using a cocktail probe approach. METHODS: Freshly isolated primary human hepatocytes were incubated with third trimester physiologic (plasma) and projected liver (ten-fold higher) concentrations of female hormones: progesterone (2 µM), estradiol (0.3 µM), estriol (0.8 µM), estrone (0.2 µM), 17α-hydroxyprogesterone (0.1 µM), and human growth hormone (0.005 µM). The metabolic activity of the hepatocytes was assessed using a cocktail of isozyme-specific P450 probe substrates (CYP1A2 (phenacetin), CYP2C9 (diclofenac), CYP2C19 (S-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (testosterone)). A validated LC-MS/MS assay was used to measure the corresponding metabolite concentrations. CYP450 protein and mRNA levels were measured using western blot and qRT-PCR, respectively. RESULTS: Female hormones at projected third-semester hepatic concentrations significantly enhanced mRNA and protein expression and increased the metabolic activity of CYP3A4. The expression and activity of other CYP450 enzymes studied were not affected by mixtures of female hormones at concentrations used. CONCLUSION: The increased activity of CYP3A4 is consistent with the clinically observed increase in clearance of CYP3A4 substrates during pregnancy. Overall expression and activity of CYP450 isozymes are differentially regulated during pregnancy.

Short-term administration of tibolone reduces inflammation and oxidative stress in the hippocampus of ovariectomized rats fed high-fat and high-fructose.

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

Follicle-stimulating hormone-mediated decline in miR-92a-3p expression in pubertal mice Sertoli cells is crucial for germ cell differentiation and fertility.

Sertoli cells (Sc) are the sole target of follicle-stimulating hormone (FSH) in the testis and attain functional maturation post-birth to significantly augment germ cell (Gc) division and differentiation at puberty. Despite having an operational microRNA (miRNA) machinery, limited information is available on miRNA-mediated regulation of Sc maturation and male fertility. We have shown before that miR-92a-3p levels decline in pubertal rat Sc. In response to FSH treatment, the expressions of FSH Receptor, Claudin11 and Klf4 were found to be elevated in pubertal rat Sc coinciding with our finding of FSH-induced decline in miR-92a-3p levels. To investigate the association of miR-92a-3p and spermatogenesis, we generated transgenic mice where such pubertal decline of miR-92a-3p was prevented by its overexpression in pubertal Sc under proximal Rhox5 promoter, which is known to be activated specifically at puberty, in Sc. Our in vivo observations provided substantial evidence that FSH-induced decline in miR-92a-3p expression during Sc maturation acts as an essential prerequisite for the pubertal onset of spermatogenesis. Elevated expression of miR-92a-3p in post-pubertal testes results into functionally compromised Sc, leading to impairment of the blood-testis barrier formation and apoptosis of pre-meiotic Gc, ultimately culminating into infertility. Collectively, our data suggest that regulation of miR-92a-3p expression is crucial for Sc-mediated induction of active spermatogenesis at puberty and regulation of male fertility.

Influence of Flaxseed (Linum usitatissimum) on Female Reproduction.

This review describes the chemical composition of flaxseed (Linum usitatissimum) and its general health effects, as well as the currently available knowledge concerning its action on the female reproductive state, functions on the ovary and ovarian cells and reproductive hormones, as well as possible constituents and extra- and intracellular mediators mediating its effects on female reproductive processes. Flaxseed contains a number of biologically active molecules, which, acting through multiple signalling pathways, can determine numerous physiological, protective and therapeutic effects of flaxseed. The available publications demonstrate the action of flaxseed and its constituents on the female reproductive system - ovarian growth, follicle development, the resulting puberty and reproductive cycles, ovarian cell proliferation and apoptosis, oo- and embryogenesis, hormonal regulators of reproductive processes and their dysfunctions. These effects can be determined by flaxseed lignans, alpha-linolenic acid and their products. Their actions can be mediated by changes in general metabolism, metabolic and reproductive hormones, their binding proteins, receptors and several intracellular signalling pathways, including protein kinases, transcription factors regulating cell proliferation, apoptosis, angiogenesis and malignant transformation. Flaxseed and its active molecules are found potentially useful for improving farm animal reproductive efficiency and treatment of polycystic ovarian syndrome and ovarian cancer.

Intratracheal instillation of respirable particulate matter elicits neuroendocrine activation.

OBJECTIVE: Inhalation of ozone activates central sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal stress axes. While airway neural networks are known to communicate noxious stimuli to higher brain centers, it is not known to what extent responses generated from pulmonary airways contribute to neuroendocrine activation. MATERIALS AND METHODS: Unlike inhalational exposures that involve the entire respiratory tract, we employed intratracheal (IT) instillations to expose only pulmonary airways to either soluble metal-rich residual oil fly ash (ROFA) or compressor-generated diesel exhaust particles (C-DEP). Male Wistar-Kyoto rats (12-13 weeks) were IT instilled with either saline, C-DEP or ROFA (5 mg/kg) and necropsied at 4 or 24 hr to assess temporal effects. RESULTS: IT-instillation of particulate matter (PM) induced hyperglycemia as early as 30-min and glucose intolerance when measured at 2 hr post-exposure. We observed PM- and time-specific effects on markers of pulmonary injury/inflammation (ROFA>C-DEP; 24 hr>4hr) as corroborated by increases in lavage fluid injury markers, neutrophils (ROFA>C-DEP), and lymphocytes (ROFA). Increases in lavage fluid pro-inflammatory cytokines differed between C-DEP and ROFA in that C-DEP caused larger increases in TNF-α whereas ROFA caused larger increases in IL-6. No increases in circulating cytokines occurred. At 4 hr, PM impacts on neuroendocrine activation were observed through depletion of circulating leukocytes, increases in adrenaline (ROFA), and decreases in thyroid-stimulating-hormone, T3, prolactin, luteinizing-hormone, and testosterone. C-DEP and ROFA both increased lung expression of genes involved in acute stress and inflammatory processes. Moreover, small increases occurred in hypothalamic Fkbp5, a glucocorticoid-sensitive gene. CONCLUSION: Respiratory alterations differed between C-DEP and ROFA, with ROFA inducing greater overall lung injury/inflammation; however, both PM induced a similar degree of neuroendocrine activation. These findings demonstrate neuroendocrine activation after pulmonary-only PM exposure, and suggest the involvement of pituitary- and adrenal-derived hormones.

Impacts of selenium nanoparticles and spirulina alga to alleviate the deleterious effects of heat stress on reproductive efficiency, oxidative capacity and immunity of doe rabbits.

Effects of dietary inclusion of spirulina platensis (SP) and selenium nanoparticles (SeNPs) combination (SP-SeNPs) on the reproductive performance in vivo and in vitro, reproductive and metabolic hormones, hemato-bichemical parameters, oxidative stress, and immunity of heat-stressed doe rabbis were evaluated. All supplements significantly increased live litter size at birth and weaning, viability rate at birth, hemoglobin and red blood cells, and plasma T3, T4, insulin, total proteins and albumin compared with control. Plasma estradiol 17-ß (pre-mating), progesterone (mid-pregnancy), and prolactin (day -7 postpartum) were significantly increased only by SeNPs (0.3, 0.4, and 0.5 mg/kg). All dietary supplements significantly reduced WBCs, cortisol, lipid profile, and improved liver and kidney functions. Immunoglobulins levels, antioxidants capacity were significantly increased, superoxide dismutase was increased by SeNPs (0.4 and 0.5 mg/kg), while malondialdehyde was reduced by 0.3, 0.4 and 0.5 SeNPs mg/kg. Sexual receptivity, pregnancy rate, viability rate at weaning, ovulation rate, and embryo quality were significantly increased by increasing SeNPs above 0.1 mg, while embryo yield was increased by >0.2 mg SeNPs/kg. A combination of SP and SeNPs, could be potentially used as a strong antioxidant to enhance heat regulation and doe rabbit reproduction via improving reproductive and metabolic hormones, antioxidant status and immunological parameters.

Pectolinarigenin shows lipid-lowering effects by inhibiting fatty acid biosynthesis in vitro and in vivo.

Pectolinarigenin is the main flavonoid compound and presents in Linaria vulgaris and Cirsium chanroenicum. In this study, RNA sequencing (RNA-seq) was applied to dissect the effect of pectolinarigenin on the transcriptome changes in the high lipid Huh-7 cells induced by oleic acid. RNA-seq results revealed that 15 pathways enriched by downregulated genes are associated with cell metabolism including cholesterol metabolism, glycerophospholipid metabolism, steroid biosynthesis, steroid hormone biosynthesis, fatty acid biosynthesis, etc. Moreover, 13 key genes related to lipid metabolism were selected. Among them, PPARG coactivator 1 beta (PPARGC1B) and carnitine palmitoyltransferase 1A (CPT1A) were found to be upregulated, solute carrier family 27 member 1(SLC27A1), acetyl-CoA carboxylase alpha (ACACA), fatty-acid synthase (FASN), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), etc. were found to be downregulated. Glycolysis/gluconeogenesis, steroid hormone biosynthesis, and fatty acid biosynthesis were all significantly downregulated, according to gene set variation analysis and gene set enrichment analysis. Besides, protein levels of FASN, ACACA, and SLC27A1 were all decreased, whereas PPARγ and CPT1A were increased. Docking models showed that PPARγ may be a target for pectolinarigenin. Furthermore, pectolinarigenin reduced serum TG and hepatic TG, and improved insulin sensitivity in vivo. Our findings suggest that pectolinarigenin may target PPARγ and prevent fatty acid biosynthesis.

Integrative physiological, critical plant endogenous hormones, and transcriptomic analyses reveal the difenoconazole stress response mechanism in wheat (Triticum aestivum L.).

Difenoconazole (DFN) is widely utilized as a fungicide in wheat production. However, its accumulation in plant tissues has a profound impact on the physiological functions of wheat plants, thus severely threatening wheat growth and even jeopardizing human health. This study aims to comprehensively analyze the dynamic dissipation patterns of DFN, along with an investigation into the physiological, hormonal, and transcriptomic responses of wheat seedlings exposed to DFN. The results demonstrated that exposure of wheat roots to DFN (10 mg/kg in soil) led to a significant accumulation of DFN in wheat plants, with the DFN content in roots being notably higher than that in leaves. Accumulating DFN triggered an increase in reactive oxygen species content, malonaldehyde content, and antioxidant enzyme activities, while concurrently inhibiting photosynthesis. Transcriptome analysis further revealed that the number of differentially expressed genes was greater in roots compared with leaves under DFN stress. Key genes in roots and leaves that exhibited a positive response to DFN-induced stress were identified through weighted gene co-expression network analysis. Metabolic pathway analysis indicated that these key genes mainly encode proteins involved in glutathione metabolism, plant hormone signaling, amino acid metabolism, and detoxification/defense pathways. Further results indicated that abscisic acid and salicylic acid play vital roles in the detoxification of leaf and root DFN, respectively. In brief, the abovementioned findings contribute to a deeper understanding of the detrimental effects of DFN on wheat seedlings, while shedding light on the molecular mechanisms underlying the responses of wheat root and leaves to DFN exposure.

α-Cyperone ameliorates depression in mammary gland hyperplasia and chronic unpredictable mild stress rat by regulating hormone, inflammation, and oxidative stress.

BACKGROUND: Hyperplasia of mammary gland (HMG) is caused by endocrine disorders, and patients are prone to anxiety and depression. α-Cyperone has a variety of pharmacological activities including antidepressant. The purpose of this study was to explore the effect and its possible mechanism of α-Cyperone on HMG-associated depression rats. METHODS: The depression model was constructed using chronic unpredictable mild stress (CUMS), while the HMG model was induced by estrogen, with or without α-Cyperone intervention. The effect of α-Cyperone on the depression-like phenotype of model rats was measured by sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). Dendritic spines density in ventral medial prefrontal cortex (vmPFC) neurons was evaluated by Golgi staining. The second pair of nipple height, diameter, organ index, and oxidative stress-related factors were analyzed. Serum sex hormone concentration, histopathological changes, inflammatory factor expression, and p65 were evaluated by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, real-time quantitative PCR and western blot, respectively. RESULTS: The sucrose preference rate, dendritic spine density decreased, and immobility time increased in CUMS rats; α-Cyperone reversed the effect of CUMS on depression-like behavior and dendritic spine density in rats. α-Cyperone reduced nipple height and diameter, uterine index, estradiol concentration, increased ovary, thymus, spleen index, progesterone, and testosterone concentration, relieved pathological damage, oxidative stress, depression-like behavior, and inflammatory reaction in HMG combine CUMS rats. In addition, α-Cyperone inhibited the phosphorylation of p65 in HMG and CUMS rats. CONCLUSIONS: α-Cyperone has an effective therapeutic effect on HMG combined with CUMS rats.