Downregulation of Klebsiella pneumoniae RND efflux pump genes following indole signal produced by Escherichia coli.

BACKGROUND: More than a century has passed since it was discovered that many bacteria produce indole, but research into the actual biological roles of this molecule is just now beginning. The influence of indole on bacterial virulence was extensively investigated in indole-producing bacteria like Escherichia coli. To gain a deeper comprehension of its functional role, this study investigated how indole at concentrations of 0.5-1.0 mM found in the supernatant of Escherichia coli stationary phase culture was able to alter the virulence of non-indole-producing bacteria, such as Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae, which are naturally exposed to indole in mixed infections with Escherichia coli. RESULTS: Biofilm formation, antimicrobial susceptibility, and efflux pump activity were the three phenotypic tests that were assessed. Indole was found to influence antibiotic susceptibly of Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae to ciprofloxacin, imipenem, ceftriaxone, ceftazidime, and amikacin through significant reduction in MIC with fold change ranged from 4 to 16. Biofilm production was partially abrogated in both 32/45 Pseudomonas aeruginosa and all eight Proteus mirabilis, while induced biofilm production was observed in 30/40 Klebsiella pneumoniae. Moreover, acrAB and oqxAB, which encode four genes responsible for resistance-nodulation-division multidrug efflux pumps in five isolates of Klebsiella pneumoniae were investigated genotypically using quantitative real-time (qRT)-PCR. This revealed that all four genes exhibited reduced expression indicated by 2^-ΔΔCT < 1 in indole-treated isolates compared to control group. CONCLUSION: The outcomes of qRT-PCR investigation of efflux pump expression have established a novel clear correlation of the molecular mechanism that lies beneath the influence of indole on bacterial antibiotic tolerance. This research provides novel perspectives on the various mechanisms and diverse biological functions of indole signaling and how it impacts the pathogenicity of non-indole-producing bacteria.

Isolation and characterization of quorum quenching bacteria from municipal solid waste and bottom ash co-disposal landfills.

Co-landfilling of bottom ash (BA) accelerates the clogging of leachate collection systems (LCSs) and increases the risk of landfill failure. The clogging was mainly associated with bio-clogging, which may be reduced by quorum quenching (QQ) strategies. This communication reports on a study of how isolated facultative QQ bacterial strains from municipal solid waste (MSW) landfills and BA co-disposal landfills. In MSW landfills, two novel QQ strains (Brevibacillus agri and Lysinibacillus sp. YS11) can degrade the signal molecule hexanoyl-l-homoserine lactone (C6-HSL) and octanoyl-l-homoserine lactone (C8-HSL), respectively. Pseudomonas aeruginosa could degrade C6-HSL and C8-HSL in BA co-disposal landfills. Moreover, P. aeruginosa (0.98) was observed with a higher growth rate (OD600) compared to that of B. agri (0.27) and Lysinibacillus sp. YS11 (0.53). These results indicated that the QQ bacterial strains were associated with leachate characteristics and signal molecules and could be used for controlling bio-clogging in landfills.

Phosphorus Regulates the Level of Signaling Molecules in Rice to Reduce Cadmium Toxicity.

Phosphorus treatment can reduce Cd accumulation and Cd toxicity in rice, but alterations in the internal regulatory network of rice during this process have rarely been reported. We have removed the effect of cadmium phosphate precipitation from the hydroponic system, treated a pair of different Cd-response rice varieties with different levels of phosphorus and cadmium and examined the changes in physiological indicators and regulatory networks. The results demonstrated that phosphorus treatment significantly reduced Cd accumulation in both types of rice, although the antioxidant systems within the two types of rice produced opposite responses. Overall, 3 mM phosphorus treatment to Cd-N decreased the expression of OsIAA17 and OsACO1 by 32% and 37%, respectively, while increasing the expression of OsNR2 by 83%; these three genes regulate the synthesis of auxin, ethylene, and nitric oxide in rice. IAA and NO levels in rice shoots increased by 24% and 96%, respectively, and these changes contribute to Cd detoxification. The cadmium transporter genes OsHMA2, OsIRT1, and OsABCC1 were significantly down-regulated in Cd-N roots after triple phosphorus treatment. These data suggest that phosphorus treatment can reduce Cd accumulation and enhance Cd resistance in rice by affecting the expression of signaling molecules.

Neural induction: Historical views and application to pluripotent stem cells.

Embryonic stem (ES) cells are a useful experimental material to recapitulate the differentiation steps of early embryos, which are usually invisible and inaccessible from outside of the body, especially in mammals. ES cells have greatly facilitated the analyses of gene expression profiles and cell characteristics. In addition, understanding the mechanisms during neural differentiation is important for clinical purposes, such as developing new therapeutic methods or regenerative medicine. As neurons have very limited regenerative ability, neurodegenerative diseases are usually intractable, and patients suffer from the disease throughout their lifetimes. The functional cells generated from ES cells in vitro could replace degenerative areas by transplantation. In this review, we will first demonstrate the historical views and widely accepted concepts regarding the molecular mechanisms of neural induction and positional information to produce the specific types of neurons in model animals. Next, we will describe how these concepts have recently been applied to the research in the establishment of the methodology of neural differentiation from mammalian ES cells. Finally, we will focus on examples of the applications of differentiation systems to clinical purposes. Overall, the discussion will focus on how historical developmental studies are applied to state-of-the-art stem cell research.

TGF-ß1 and its signal molecules: are they correlated with the elasticity characteristics of breast lesions?

BACKGROUND: Shear wave elastography can evaluate tissue stiffness. Previous studies showed that the elasticity characteristics of breast lesions were related to the components of extracellular matrix which was regulated by transforming growth factor beta 1(TGF-ß1) directly or indirectly. However, the correlation of the expression level of TGF-ß1, its signal molecules and elasticity characteristics of breast lesions have rarely been reported. The purpose of this study was to investigate the correlation between the expression level of TGF-ß1, its signal molecules, and the elasticity characteristics of breast lesions. METHODS: 135 breast lesions in 130 patients were included. Elasticity parameters, including elasticity modulus, the elasticity ratio, the "stiff rim sign", were recorded before biopsy and surgical excision. The expression levels of TGF-ß1 and its signal molecules, including Smad2/3, Erk1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase 2 (JNK2), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB/AKT) were detected by immunohistochemistry. The diagnostic performance of the expression level of those molecules and their correlation with the elasticity characteristics were analyzed. RESULTS: Elasticity parameters and the expression levels of TGF- ß1 and its signal molecules of benign lesions were lower than those of malignant lesions (P<0.0001). The expression levels of TGF- ß1 and its signal molecules were correlated with elasticity parameters. The expression levels of TGF- ß1 and its signal molecules in lesions with "stiff rim sign" were higher than those without "stiff rim sign" (P<0.05). And the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were correlated with that of TGF- ß1. The area under the curve for receiver operator characteristic curve of TGF-ß1 and its signal molecules in the differentiation of malignant and benign breast lesions ranged from 0.920-0.960. CONCLUSIONS: The expression levels of TGF-ß1, its signal molecules of breast lesions showed good diagnostic performance and were correlated with the elasticity parameters. The expression levels of signal molecules were correlated with that of TGF- ß1, which speculated that TGF- ß1 might play an important role in the regulation of breast lesion elasticity parameters and multiple signal molecule expressions.

Nonlinear thermodynamics of biological signal transduction for predicting conservation of entropy production rate.

Cell signal transduction is an example of a nonequilibrium phenomenon. In this study, a nonequilibrium nonlinear thermodynamic model was formulated. First, we obtained a condition in which the Onsager's reciprocity theorem holds in the signal transduction. Second, it was found that the entropy production rate per signal molecule is conserved through signal transduction. Finally, it was determined that when Onsager's reciprocity theorem does not hold, fluctuation circulation is given by the phosphorylation rate of signal molecules. The simple relation implies that the fluctuation circulation can be an essential quantity of the signal transduction amount. These results expand the limit of nonequilibrium thermodynamics and can be used to provide ideas for signal transduction quantification.

Methyl Jasmonate Induced Oxidative Stress and Accumulation of Secondary Metabolites in Plant Cell and Organ Cultures.

Recently, plant secondary metabolites are considered as important sources of pharmaceuticals, food additives, flavours, cosmetics, and other industrial products. The accumulation of secondary metabolites in plant cell and organ cultures often occurs when cultures are subjected to varied kinds of stresses including elicitors or signal molecules. Application of exogenous jasmonic acid (JA) and methyl jasmonate (MJ) is responsible for the induction of reactive oxygen species (ROS) and subsequent defence mechanisms in cultured cells and organs. It is also responsible for the induction of signal transduction, the expression of many defence genes followed by the accumulation of secondary metabolites. In this review, the application of exogenous MJ elicitation strategies on the induction of defence mechanism and secondary metabolite accumulation in cell and organ cultures is introduced and discussed. The information presented here is useful for efficient large-scale production of plant secondary metabolites by the plant cell and organ cultures.

Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH, Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions.

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.

Early Changes in Nutritional Conditions Affect Formation of Synthetic Mutualism Between Chlorella sorokiniana and the Bacterium Azospirillum brasilense.

The effect of three different nutritional conditions during the initial 12 h of interaction between the microalgae Chlorella sorokiniana UTEX 2714 and the plant growth-promoting bacterium Azospirillum brasilense Cd on formation of synthetic mutualism was assessed by changes in population growth, production of signal molecules tryptophan and indole-3-acetic acid, starch accumulation, and patterns of cell aggregation. When the interaction was supported by a nutrient-rich medium, production of both signal molecules was detected, but not when this interaction began with nitrogen-free (N-free) or carbon-free (C-free) media. Overall, populations of bacteria and microalgae were larger when co-immobilized. However, the highest starch production was measured in C. sorokiniana immobilized alone and growing continuously in a C-free mineral medium. In this interaction, the initial nutritional condition influenced the time at which the highest accumulation of starch occurred in Chlorella, where the N-free medium induced faster starch production and the richer medium delayed its accumulation. Formation of aggregates made of microalgae and bacteria occurred in all nutritional conditions, with maximum at 83 h in mineral medium, and coincided with declining starch content. This study demonstrates that synthetic mutualism between C. sorokiniana and A. brasilense can be modulated by the initial nutritional condition, mainly by the presence or absence of nitrogen and carbon in the medium in which they are interacting.

[Aging of skin fibroblasts: genetic and epigenetic factors.]

Gerontocosmetology is the rapid developing knowledge area that has a very large applied meaning. Herewith a lot of information about skin aging and geroprotectors for skin rejuvenation hasn't a scientific background. Thus, understanding the fundamental mechanisms of skin aging becomes the actual task of molecular gerontology. Skin fibroblasts are the polyfunctional cell population that synthesize a number of biologically active substances and participate in maintaining of extracellular matrix homeostasis, skin hydratation and endocrine and immune function. In the review genetic (accumulation of nuclear and mitochondrial DNA mistakes) and epigenetic factors of skin fibroblasts aging are described. Role of AP-1, NF-κB, c-jun, CCN1, TGF-ß, TNF-α, MMP-1, MMP-3, MMP-8, MMP-9 and glycation in skin fibroblasts aging are discussed. There are some data about decreasing of skin fibroblasts ability to migration and synthesis of paxillins and aquaporin-3 (AQP3) during aging. Role of hormonal regulation in skin fibroblasts aging are described. Geroprotective action of melatonin to skin fibroblasts are showed. Reviewed molecular-cellular aspects of skin fibroblasts aging can be take into consideration for scientific background of using of cosmetic products for retarding of skin aging rate.

Journey of oocyte from metaphase-I to metaphase-II stage in mammals.

In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important since oocyte extrude first polar body (PB-I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M-I to M-II stage and extrusion of PB-I remain ill understood. Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen-activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M-I to M-II stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation of anaphase-promoting complex/cyclosome (APC/C). The active APC/C destabilizes maturation promoting factor (MPF) and induces meiotic resumption. Several signal molecules such as, c-Jun N-terminal kinase (JNK2), SENP3, mitotic kinesin-like protein 2 (MKlp2), regulator of G-protein signaling (RGS2), Epsin2, polo-like kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation. Rho family GTPase is another enzyme that along with cell division cycle (Cdc42) to form actomyosin contractile ring required for chromosomal segregation. In the presence of origin recognition complex (ORC4), eccentrically localized haploid set of chromosomes trigger cortex differentiation and determine the division site for polar body formation. The actomyosin contractile activity at the site of division plane helps to form cytokinetic furrow that results in the formation and extrusion of PB-I. Indeed, oocyte journey from M-I to M-II stage is coordinated by several factors and pathways that enable oocyte to extrude PB-I. Quality of oocyte directly impact fertilization rate, early embryonic development, and reproductive outcome in mammals.

N-Acyl-homoserine lactones and autoinducer-2-mediated quorum sensing during wastewater treatment.

Bacteria can coordinate and synchronize activities through a cell density-dependent regulatory mechanism called quorum sensing (QS). Bacteria can measure their population by the synthesis, secretion, and perception of QS signal molecules to regulate specific gene expression when the population reaches a critical threshold. QS participates in various microbial processes such as marine organism bioluminescence, bacterial biofilm formation, and virulence factor expression. The use of QS systems mediated by N-acyl-homoserine lactones and autoinducer-2 has been recently recognized as a promising regulatory approach in environmental science and technology that can intrinsically promote the profound comprehension of wastewater treatment from a microbiology perspective. This article reviewed the study of QS in several environmental systems in wastewater treatment, including systems of aerobic granular sludge, biological nitrogen removal, and bioaugmentation, while several future prospects and suggestions are proposed on the basis of current studies.

Maturation promoting factor destabilization mediates human chorionic gonadotropin induced meiotic resumption in rat oocytes.

Human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone (LH) and triggers meiotic maturation and ovulation in mammals. The mechanism by which hCG triggers meiotic resumption in mammalian oocytes remains poorly understood. We aimed to find out the impact of hCG surge on morphological changes, adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell division cycle 25B (Cdc25B), Wee1, early mitotic inhibitor 2 (Emi2), anaphase-promoting complex/cyclosome (APC/C), meiotic arrest deficient protein 2 (MAD2), phosphorylation status of cyclin-dependent kinase 1 (Cdk1), its activity and cyclin B1 expression levels during meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in cumulus oocyte complexes (COCs). Our data suggest that hCG surge increased cyclic nucleotides level in encircling granulosa cells but decreased their level in oocyte. The reduced intraoocyte cyclic nucleotides level is associated with the decrease of Cdc25B, Thr161 phosphorylated Cdk1 and Emi2 expression levels. On the other hand, hCG surge increased Wee1, Thr14/Tyr15 phosphorylated Cdk1, APC/C as well as MAD2 expression levels. The elevated APC/C activity reduced cyclin B1 level. The changes in phosphorylation status of Cdk1 and reduced cyclin B1 level might have resulted in maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggered resumption of meiosis from diplotene as well as M-II arrest in rat oocytes.

Moderate increase of reactive oxygen species triggers meiotic resumption in rat follicular oocytes.

AIM: The mammalian ovary generates reactive oxygen species (ROS) on an extraordinary scale; however, the role of ROS during meiotic cell cycle progression in follicular oocytes remains poorly understood. The present study was aimed to determine whether a moderate increase of ROS level in the ovary is beneficial for meiotic resumption from diplotene arrest in follicular oocytes. METHODS: Cumulus oocyte complexes were collected from the ovaries of female rats that had been treated with either: (i) pregnant mare's serum gonadotrophin; or (ii) pregnant mare's serum gonadotrophin + human chorionic gonadotrophin. We analyzed morphological changes, ROS and hydrogen peroxide levels, catalase activity, 3',5'-cyclic adenosine monophosphate and 3',5'-cyclic guanosine monophosphate levels, Thr14/Tyr15, Th-161, total cyclin-dependent kinase 1 (Cdk1) and cyclin B1 levels. RESULTS: Human chorionic gonadotrophin treatment induced meiotic resumption from diplotene arrest and extrusion of first polar body in cumulus oocyte complexes collected from ovaries and cultured for 3 h in vitro. Meiotic resumption from diplotene arrest was associated with increased ROS and hydrogen peroxide levels but decreased 3',5'-cyclic adenosine monophosphate as well as 3',5'-cyclic guanosine monophosphate levels. The reduced cyclic nucleotide levels were associated with decreased Thr161 phosphorylated Cdk1 and cyclin B1 level but increased Thr14/Tyr15 phosphorylated Cdk1 level leading to maturation promoting factor destabilization. Destabilized maturation-promoting factor triggered meiotic resumption from diplotene arrest and progression to metaphase-I as well as metaphase-II stage in follicular oocytes. CONCLUSION: Our findings suggest that a moderate increase of ROS in the ovary is beneficial for meiotic resumption from diplotene arrest and extrusion of first polar body in follicular oocytes.

Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro.

The effect peptides KE, KED, AED and AEDG on proliferation (Ki-67), regeneration and aging (CD98hc), apoptosis (caspase-3), and extracellular matrix remodeling (MMP-9) in skin fibroblasts during their aging in culture were studied by immunofluorescent confocal microscopy. All studied peptides inhibited MMP-9 synthesis that increases during aging of skin fibroblasts and enhanced the expression of Ki-67 and CD98hc that are less intensively synthesized during cell aging. Peptides AED and AEDG suppressed caspase-dependent apoptosis that increases during aging of cell cultures.

Changes in signal molecules and maturation promoting factor levels associate with spontaneous resumption of meiosis in rat oocytes.

The present study was aimed to find out changes in signal molecules and maturation promoting factor (MPF) levels during meiotic cell cycle progression from diplotene and metaphase-II (M-II) arrest, a period during which oocyte achieves meiotic competency. Data suggest that high levels of adenosine 3'-5'-cyclic monophosphate (cAMP), guanosine 3'-5'-cyclic monophosphate (cGMP), and nitric oxide (NO) are associated with diplotene arrest, while reduction in their levels correlates with reduced MPF level and meiotic resumption from diplotene arrest. On the other hand, increased intracellular NO, calcium (Ca(2+) ) as well as hydrogen peroxide (H2 O2 ) levels correlate with decreased cAMP, Thr-161 phosphorylated cyclin-dependent kinase-1 (Cdk1) as well as cyclin B1 levels. The decreased Thr-161 phosphorylated Cdk1 and cyclin B1 level reduce MPF level leading to exit from M-II arrest in oocytes cultured in vitro. These data suggest that the decrease of cAMP level and increase of cytosolic free Ca(2+) as well as H2 O2 levels associate with the reduced MPF level and meiotic resumption from diplotene arrest. On the other hand, increase of NO, cGMP, Ca(2+) as well as H2 O2 levels are associated with reduced MPF and spontaneous exit from M-II arrest in rat oocytes cultured in vitro.

Effects of Tai Chi exercise on blood pressure and plasma levels of nitric oxide, carbon monoxide and hydrogen sulfide in real-world patients with essential hypertension.

Objective was to investigate the effects of Tai Chi exercise on nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) levels, and blood pressure (BP) in patients with essential hypertension (EH). EH patients were assigned to the Tai Chi exercise group (HTC, n = 24), and hypertension group (HP, n = 16) by patients' willingness. Healthy volunteers matched for age and gender were recruited as control (NP, n = 16). HTC group performed Tai Chi (60 min/d, 6 d/week) for 12 weeks. Measurements (blood glucose, cholesterol, NO, CO, H2S and BP) were obtained at week 0, 6, and 12. SBP, MAP, and low-density lipoprotein cholesterol levels decreased, and high-density lipoprotein cholesterol levels increased by week 12 in the HTC group (all p < 0.05 versus baseline). Plasma NO, CO, and H2S levels in the HTC group were increased after 12 weeks (all p < 0.05 versus baseline). SBP, DBP and MAP levels were significantly lower in the HTC than in the HP group (all p < 0.05). However, no changes were observed in the HP and NP groups. Correlations were observed between changes in SBP and changes in NO, CO and H2S (r = -0.45, -0.51 and -0.46, respectively, all p < 0.05), and between changes in MAP and changes in NO, CO and H2S (r = -0.36, -0.45 and -0.42, respectively, all p < 0.05). In conclusion, Tai Chi exercise seems to have beneficial effects on BP and gaseous signaling molecules in EH patients. However, further investigation is required to understand the exact mechanisms underlying these observations, and to confirm these results in a larger cohort.

Identification and analysis of the salt tolerant property of AHL lactonase (AiiATSAWB ) of Bacillus species.

Bacterial biofilms communicate by a process called Quorum Sensing. Gram negative bacterial pathogens specifically talk through the production, detection, and response to the signal or autoinducer called Acyl Homoserine Lactones. Bacterial lactonases are important AHL hydrolysing or quorum quenching enzymes. The present study deals with ten endospore forming gram positive isolates of the saltern soil. Preliminary screening for Quorum Quenching activity with the QS Inhibition indicator strain Chromobacterium violaceum ATCC 12472, showed positive activity in four isolates namely TS2, TS16, TSAWB, and TS53B. AHL lactonase (AiiA) specific primers amplified Acyl Homoserine Lactone lactonase gene in the TSAWB genome alone. Phylogenetic relationship of the identified AiiATSAWB confirmed its evolutionary relationship with bacterial AiiA like AHL lactonase of the metallo-beta-lactamase super family. Our in vitro AHL hydrolysis assay under wide percentage (0-5) of salt solutions with TSAWB isolate and also its intracellular soluble protein fraction showed halotolerant AHL hydrolysis ability of the AiiATSAWB enzyme. In silico determination of putative tertiary structure, the ESBRI derived conserved salt bridges, aminoacid residue characterization with high mole percent of acidic and hydrophobic residues reaffirmed the halotolerant ability of the enzyme. So we propound the future use of purified AiiATSAWB , as hypertonic suspension for inhalation to substitute the action of inactivated host's paraoxonase in treating Pseudomonas aeruginosa infection in cystic fibrosis patients.

[Signal molecules of endometrium: gerontological and general pathhological aspects].

The review describes neuro-immuno-endocrine signal molecules expression in human endometrial cells in the normal conditions, in the pathology and during aging. Human endometrial cells synthesizes estrogen, progesterone, estradiol, progestin, cell adhesion molecules (integrines α1ß1, α4ß1, αVß3, L-selectin, Е-catgerin, MUC1), grow factors (TGF, EGF, HB-EGF, IGF), cytokines (IL-1, IL-2, INF-α, IL-12, СХСL10, CXCL11, CXCR3), various immune cells markers (CD68, CD105, CD163, CD16, CD56, CD4, CD8), heat shock proteins (HSP60, HSP70, HSP90, VEGF, MMP). Changes of this molecules expression level are the base of the social significant diseases as endometriosis, endometrial cancer and infertility. Thus, the investigation of neuro-immuno-endocrine interactions in endometrial cells can be used for new drugs creating, in differential diagnostics of endometrial cancer and increasing of extracorporal fertilization success.

Gamma-aminobutyric acid as a regulator of astaxanthin production in Haematococcus lacustris under salinity: Exploring physiology, signaling, autophagy, and multi-omics landscape.

Haematococcus lacustris-derived natural astaxanthin has significant commercial value, but stressful conditions alone impair cell growth and reduce the total productivity of astaxanthin in industrial settings. This study used gamma-aminobutyric acid (GABA) to increase biomass, astaxanthin productivity, and tolerance to salinity. GABA under NaCl stress enhanced the biomass to 1.76 g/L, astaxanthin content to 30.37 mg g-1, and productivity to 4.10 mg/L d-1, outperforming the control. Further analysis showed GABA enhanced nitrogen assimilation, Ca2+ level, and cellular GABA content, boosting substrate synthesis, energy metabolism, osmoregulation, autophagy, and antioxidant defenses. GABA also activated signaling pathways involving phytohormones, cAMP, cGMP, and MAPK, aiding astaxanthin synthesis. The application of biomarkers (ethylene, salicylic acid, trans-zeatin) and an autophagy inhibitor cooperated with GABA to further enhance the total astaxanthin productivity under NaCl stress. Combining GABA with 25 µM salicylic acid maximized astaxanthin yield at 4.79 mg/L d-1, offering new strategies for industrial astaxanthin production.