Retrotransposon SINEs in age-related diseases: Mechanisms and therapeutic implications.

Retrotransposons are self-replicating genomic elements that move from one genomic location to another using a "copy-and-paste" method involving RNA intermediaries. One family of retrotransposon that has garnered considerable attention for its association with age-related diseases and anti-aging interventions is the short interspersed nuclear elements (SINEs). This review summarizes current knowledge on the roles of SINEs in aging processes and therapies. To underscore the significant research on the involvement of SINEs in aging-related diseases, we commence by outlining compelling evidence on the classification and mechanism, highlighting implications in age-related phenomena. The intricate relationship between SINEs and diseases such as neurodegenerative disorders, heart failure, high blood pressure, atherosclerosis, type 2 diabetes mellitus, osteoporosis, visual system dysfunctions, and cancer is explored, emphasizing their roles in various age-related diseases. Recent investigations into the anti-aging potential of SINE-targeted treatments are examined, with particular attention to how SINE antisense RNA mitigate age-related alterations at the cellular and molecular levels, offering insights into potential therapeutic targets for age-related pathologies. This review aims to compile the most recent advances on the multifaceted roles of SINE retrotransposons in age-related diseases and anti-aging interventions, providing valuable insights into underlying mechanisms and therapeutic avenues for promoting healthy aging.

Understanding the intricacies of cellular senescence in atherosclerosis: Mechanisms and therapeutic implications.

Cardiovascular disease is currently the largest cause of mortality and disability globally, surpassing communicable diseases, and atherosclerosis is the main contributor to this epidemic. Aging is intimately linked to atherosclerosis development and progression, however, the mechanism of aging in atherosclerosis is not well known. To emphasize the significant research on the involvement of senescent cells in atherosclerosis, we begin by outlining compelling evidence that indicates various types of senescent cells and SASP factors linked to atherosclerotic phenotypes. We subsequently provide a comprehensive summary of the existing knowledge, shedding light on the intricate mechanisms through which cellular senescence contributes to the pathogenesis of atherosclerosis. Further, we cover that senescence can be identified by both structural changes and several senescence-associated biomarkers. Finally, we discuss that preventing accelerated cellular senescence represents an important therapeutic potential, as permanent changes may occur in advanced atherosclerosis. Together, the review summarizes the relationship between cellular senescence and atherosclerosis, and inspects the molecular knowledge, and potential clinical significance of senescent cells in developing senescent-based therapy, thus providing crucial insights into their biology and potential therapeutic exploration.

Unraveling the roles of modified nanomaterials in nano enabled agriculture.

Nanotechnology has emerged as a key empowering technology for agriculture production due to its higher efficiency and accurate target delivery. However, the sustainable and effective application of nanotechnology requires nanomaterials (NMs) to have higher stability and less aggregation/coagulation at the reaction sites. This can ideally be achieved by modifying NMs with some surfactants or capping agents to ensure higher efficiency. These modified nanomaterials (MNMs) stabilize the interface where NMs interact with their medium of preparation and showed a significant improvement in mobility, reactivity, and controlled release of active ingredients for nano-enabled agriculture. Several environmental factors (e.g., pH, organic matter and the oxidation-reduction potential) could alter the interaction of MNMs with agricultural plants. Firstly, this novel review article introduces production technologies and a few frequently used modification agents in synthesizing MNMs. Next, we critically elaborate the leveraging progress in the modified nano-enabled agronomy and unveil their phytoremediation potential. Lastly, we propose a framework to overcome current challenges and develop a strategy for safe, effective and acceptable applications of MNMs in nano-enabled agriculture. However, the long-term effectiveness and reactivity of MNMs should be investigated to assess their technology effectiveness and optimize the process design to draw definite conclusions.

Modifying engineered nanomaterials to produce next generation agents for environmental remediation.

The application of pristine nanomaterials (PNMs) for environment remediation remains challenging due to inherently high potential for aggregation, low stability, sub-optimum efficiency, and non-uniformity in size and toxicity. Conversely, modified nanomaterials (MNMs) approaches have shown significant potential to enhance the technical and economic efficiency of conventional nanoscale remediation strategies by decreasing aggregation of nanomaterials by imparting electrostatic, electrosteric or steric repulsion between particles. Furthermore, the solubility enhancing agents in MNMs have been shown to increase metal bioavailability and accelerate the breakdown of pollutants. As such, it is imperative to modify nanomaterials for unlocking their full potential and expanding their range of applications. However, there is no comprehensive review in the literature that evaluates the efficacy and environmental impact of MNMs against PNMs in the environment. This critical review identifies major barriers preventing the widescale application of nano-enabled remediation and discusses strategies to increase the stability and activity of nanomaterials at reaction sites. The higher reactivity and versatility of MNMs, along with novel properties and functionalities, enable effective removal of a range of chemical pollutants from complex environmental matrices. Additionally, MNMs show significant improvement in mobility, reactivity, and controlled and targeted release of active ingredients for in situ remediation. However, the uncertainties associated with the adverse effects of some modification agents of MNMs are not well-understood, and require further in-depth investigations. Overall, our findings show that MNMs are potentially more efficient, cost-effective, and resilient for remediation of soil and sediment, water, and air pollution than PNMs. The possible action mechanisms of MNMs have been demonstrated for different environmental compartments. Conclusively, this work provides a path forward for developing effective nano-enabled remediation technologies with MNMs, which are widely applicable to a range of environmental contamination scenarios.

Effect of a Multistrain Probiotic on Feline Gut Health through the Fecal Microbiota and Its Metabolite SCFAs.

With the increasing awareness of raising pets following scientific methods, people are becoming increasingly more interested in the nutrition and health of pets, especially their intestinal health, which has become a research hotspot. Both Saccharomyces boulardii and Pediococcus acidilactici are probiotics with strong probiotic properties that can maintain the balance of intestinal flora. However, the role of Saccharomyces boulardii and Pediococcus acidilactici in felines has not been comprehensively studied to date. The aim of this study is to investigate the effect of multistrain probiotics consisting of Saccharomyces boulardii and Pediococcus acidilactici on the gut health of felines by modulating gut microbes and the production of metabolite SCFAs. The results show that the multistrain probiotic did not alter the intestinal microbial diversity and structure of short-haired domestic cats, promoted the colonization of beneficial bacteria, increased the levels of microbiota-derived SCFAs and fecal antioxidants, and reduced the levels of fecal inflammatory markers. In conclusion, the use of a multistrain probiotic in healthy, short-haired domestic cats can promote gut health by modulating gut microbes, improving microbiota-derived SCFA production, reducing inflammatory conditions, and improving antioxidant status. These results provide new insights for further exploration of the role of probiotics in the gut microbiome of cats.

Non-Esterified Fatty Acid-Induced Apoptosis in Bovine Granulosa Cells via ROS-Activated PI3K/AKT/FoxO1 Pathway.

Non-esterified fatty acid (NEFA), one of negative energy balance (NEB)'s most well-known products, has a significant impact on cows' reproductive potential. Our study used an in vitro model to investigate the deleterious effects of NEFA on bovine granulosa cells (BGCs) and its underlying molecular mechanism. The results showed that high levels of NEFA led to the accumulation of reactive oxygen species (ROS), increased the expression of apoptosis-related factors such as Bcl2-Associated X/B-cell lymphoma-2 (Bax/Bcl-2) and Caspase-3, and down-regulated steroid synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP-1), cytochrome P450c17 (CYP17), and cytochrome P450 aromatase (CYP19), to promote oxidative stress, cell apoptosis, and steroid hormone synthesis disorders in BGCs. In addition, NEFA significantly inhibited phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT) activity and increased forkhead box O1 (FoxO1) expression. To further explore the role of the PI3K/AKT/FoxO1 signaling pathway in NEFA, we found that pretreatment with AKT-specific activator SC79 (5 mg/mL) for 2 h or transfection with FoxO1 knockdown siRNA in BGCs could alleviate the negative effects of NEFA treatment by decreasing Bax/Bcl-2 ratio and Caspase-3 expression, and upregulating SREBP-1, CYP17, and CYP19 expression. Meanwhile, SC79 significantly inhibited NEFA-induced dephosphorylation and massive nuclear translocation of FoxO1. Taken together, the NEFA induced oxidative stress, apoptosis, and steroid hormone synthesis disorders in BGCs by inhibiting the PI3K/AKT pathway that regulates FoxO1 phosphorylation and nuclear translocation. Our findings help to clarify the molecular mechanisms underlying the negative effects of high levels of NEFA on BGCs.

CDK5RAP3, a key defender of udder, modulates NLRP3 inflammasome activation by regulating autophagolysosome degradation in S. agalactiae-infected mastitis.

Streptococcus agalactiae, as one of the main pathogens of clinical and subclinical mastitis, affects animal welfare and leads to huge economic losses to farms due to the sharp decline in milk yield. However, both the real pathogenic mechanisms of S. agalactiae-induced mastitis and the regulator which controls the inflammation and autophagy are largely unknown. Served as a substrate of ubiquitin-like proteins of E3 ligase, CDK5RAP3 is widely involved in the regulation of multiple signaling pathways. Our findings revealed that CDK5RAP3 was significantly down-regulated in mastitis infected by S. agalactiae. Surprisingly, inflammasome activation was triggered by CDK5RAP3 knockdown: up-regulated NLRP3, IL1ß and IL6, and cleaved caspase1 promoting by NF-κB, thereby resulting in pyroptosis. Additionally, the accumulation of autophagy markers (LC3B and p62) after CDK5RAP3 knockdown suggested that the autophagolysosome degradation pathway was inhibited, thereby activating the NF-κB pathway and NLRP3 inflammasome. Hence, our findings suggest that downregulation or ablation of CDK5RAP3 inhibits autophagolysosome degradation, causes inflammation by activating the NF-κB /NLRP3 inflammasome, and triggers cell death. In conclusion, CDK5RAP3 holds the key to understanding the interaction between autophagy and immune responses, its anti-inflammatory role in this study will throw new light on the clinical drug discovery to cure S. agalactiae mastitis.

Stem Cell-Based Therapeutic Strategies for Premature Ovarian Insufficiency and Infertility: A Focus on Aging.

Reproductive aging is on the rise globally and inseparable from the entire aging process. An extreme form of reproductive aging is premature ovarian insufficiency (POI), which to date has mostly been of idiopathic etiology, thus hampering further clinical applications and associated with enormous socioeconomic and personal costs. In the field of reproduction, the important functional role of inflammation-induced ovarian deterioration and therapeutic strategies to prevent ovarian aging and increase its function are current research hotspots. This review discusses the general pathophysiology and relative causes of POI and comprehensively describes the association between the aging features of POI and infertility. Next, various preclinical studies of stem cell therapies with potential for POI treatment and their molecular mechanisms are described, with particular emphasis on the use of human induced pluripotent stem cell (hiPSC) technology in the current scenario. Finally, the progress made in the development of hiPSC technology as a POI research tool for engineering more mature and functional organoids suitable as an alternative therapy to restore infertility provides new insights into therapeutic vulnerability, and perspectives on this exciting research on stem cells and the derived exosomes towards more effective POI diagnosis and treatment are also discussed.

Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli.

Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli.

Nutrient sensing mechanism of short-chain fatty acids in mastitis control.

Bovine mastitis is a disease that is widespread in dairy cows worldwide, and its impact is significant due to economic losses at all levels of the dairy value chain. For a long time, antibiotics have been the main tool for curing mastitis, however the cure rate is not very high, and sometime side effects may occur. Therefore, an in-depth understanding of mastitis and effective solutions are urgently needed to resolve the problem that in what way to prevent and treat mastitis in order to protect the profitability of dairy farms. The importance of diet in the regulation of health are not novel. Dietary control of the intestinal flora provides a promising approach to prevent or treat certain deadly diseases. Ample amount of studies has been conducted on the role of short-chain fatty acids (SCFAs) in the maintenance of health. SCFAs are the type of dietary substance that has the ability to restore blood-milk barrier permeability, inhibit the development of mammary inflammation, and are also effective epigenomic modifiers with histone deacetylases inhibitory activity. To date, the detailed mechanism of action of SCFAs in treating mastitis is unclear, but preliminary evidences are emerging. To assess the effectiveness of this recommendation, we examined the overall mammary gland health knowledge related to SCFAs by scrutinizing their potential role and evaluating its compatibility with the immunobiology of mammary gland inflammation. We then considered preliminary in vivo and in vitro experiments and analyzed the literature on the subject. Here, we outline the production of SCFAs and its protective effect on the mammary gland, with particular emphasis on their relevance to mastitis. In addition, we also discussed the therapeutic potential of SCFAs for mammary gland inflammation. Expectantly, this theory will provide new perception for the treatment of mastitis and other infectious diseases.

Nrf2 Activation and NF-Kb & caspase/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells.

Mastitis, an inflammation of the mammary gland, is a complex disease that affects the health of dairy cows worldwide. Sodium butyrate (SB) is a short-chain fatty acid that has recently been shown to have antioxidant, anti-inflammatory and anti-apoptotic potential in various cells types, although its role in bovine mammary epithelial cells (bMECs) has not been comprehensively reported. Therefore, the aim of this study was to assess the protective effect of sodium butyrate on Lipopolysaccharide (LPS)-induced mastitis model in vitro and to elucidate the possible underlying molecular mechanisms. The in vitro mastitis model was designed to investigate the regulatory effect of SB on LPS-induced inflammatory conditions in bMECs, with particular emphasis on oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. The results showed that SB co-treatment markedly prevented LPS-induced death of bMECs in a concentration-dependent manner. In addition, SB attenuated LPS-induced oxidative stress (OS) (Increased Intracellular ROS, MDA, and decreased SOD, GSH-Px and CAT activity), thereby reduced inflammation (increased expression of IL-6, IL-Iß, and TNF-α), and apoptosis (Increased the expression of caspases and Bax and decreased Bcl-2) via inhibiting NF-kB and caspase/bax signaling pathways. Furthermore, the protective effect of SB was also associated with the activation of endogenous antioxidant system (Nrf2, Keap1, NQO-1 and HO-1). Nrf2 silencing significantly abolished the protective effect of SB on bMECs. In conclusion, our findings suggest that SB has a significant protective effect on LPS-induced OS, inflammatory responses and apoptosis by activating Nrf2 and inhibiting NF-kB and ROS-mediated mitochondrial dysfunction. These results propose that SB may be an important regulator of OS and its subsequent inflammatory responses, and thus could be used as a therapeutic agent for bovine mastitis.

CDK5RAP3, an essential regulator of checkpoint, interacts with RPL26 and maintains the stability of cell growth.

PURPOSE AND MATERIALS: CDK5RAP3 (CDK5 regulatory subunit associated protein 3) was originally identified as a binding protein of CDK5. It is a crucial gene controlling biological functions, such as cell proliferation, apoptosis, invasion, and metastasis. Although previous studies have also shown that CDK5RAP3 is involved in a variety of signalling pathways, however, the mechanism of CDK5RAP3 remains largely undefined. This study utilized MEFs from conditional knockout mice to inhibit CDK5RAP3 and knockdown CDK5RAP3 in MCF7 to explore the role of CDK5RAP3 in cell growth, mitosis, and cell death. RESULTS: CDK5RAP3 was found to be widely distributed throughout the centrosome, spindle, and endoplasmic reticulum, indicating that it is involved in regulating a variety of cellular activities. CDK5RAP3 deficiency resulted in instability of cell growth. CDK5RAP3 deficiency partly blocks the cell cycle in G2 /M by downregulating CDK1 (Cyclin-dependent kinase 1) and CCNB1 (Cyclin B1) expression levels. The cell proliferation rate was decreased, thereby slowing down the cell growth rate. Furthermore, the results showed that CDK5RAP3 interacts with RPL26 (ribosome protein L26) to regulate the mTOR pathway. CDK5RAP3 and RPL26 deficiency inhibited mTOR/p-mTOR protein and induce autophagy, resulting in an upregulation of the percentage of apoptosis, and the upregulated percentage of apoptosis also slowed cell growth. CONCLUSIONS: Our experiments show that CDK5RAP3 interacts with RPL26 and maintains the stability of cell growth. It shows that CDK5RAP3 plays an important role in cell growth and can be used as the target of gene medicine.

The Effect of Inhibin Immunization in Seminiferous Epithelium of Yangzhou Goose Ganders: A Histological Study.

The current study investigated the effect of inhibin immunization on germ cell numbers (spermatogonia, spermatocytes, round, and elongated spermatids), seminiferous tubules (ST) diameter, Johnsen's score, epithelial height (µm), luminal tubular diameter (µm), and number of ST per field (ST/field) of Yangzhou goose ganders. Histological evaluation showed apoptosis and regression of testes after inhibin (INH) immunization, with a concomitantly marked reduction in the round and elongated spermatids in the experiment (INH) group compared to the control group. The diameter of seminiferous tubules (ST) and epithelial height (EH) were positively correlated at 181, 200, and 227 days of age. In comparison, luminal tubular diameter (LD) was negatively correlated on day 227 to ST diameter and epithelial height. On day 227, many seminiferous tubules per field (ST/field) were negatively correlated to ST diameter, EH, and LD. INH immunization elevated ST diameter, EH, and LD, while Johnsen's score and number of ST/field had reciprocal expression. In conclusion, the concomitant effect of INH immunization and seasonality in breeding regressed germ cells and damaged spermatogenesis in seminiferous epithelium Yangzhou ganders.

Ufbp1, a Key Player of Ufm1 Conjugation System, Protects Against Ketosis-Induced Liver Injury via Suppressing Smad3 Activation.

The dairy cattle suffer from severe liver dysfunction during the pathogenesis of ketosis. The Ufm1 conjugation system is crucial for liver development and homeostasis. Ufm1 binding protein (Ufbp1) is a putative Ufm1 target and an integral component, but its role in ketosis-induced liver injury is unclear so far. The purpose of this study is to explore the key role of Ufbp1 in liver fibrosis caused by ketosis in vivo and in vitro. Liver tissues were collected from ketotic cows and Ufbp1 conditional knockout (CKO) mice in vivo. However, Ufbp1 -/- mouse embryonic fibroblast cells and Hela cells were used for in vitro validation. Subsequently, various assays were performed to reveal the underlying molecular mechanisms of the Ufbp1 protective effect. In this study, hepatic fibrosis, endoplasmic reticulum (ER) stress, and apoptosis were reported in the liver of ketotic cows, fibrotic markers (alpha-smooth muscle actin, Collagen1) and ER stress markers (glucose-regulated protein 78, CEBP homologous protein) were upregulated remarkably, and the apoptosis-related genes (Bcl2, Bax) were in line with expectations. Interestingly, Ufbp1 expression was almost disappeared, and Smad2/Smad3 protein was largely phosphorylated in the liver of ketotic cows, but Ufbp1 deletion caused Smad3 phosphorylation apparently, rather than Smad2, and elevated ER stress was observed in the CKO mice model. At the cellular level, Ufbp1 deficiency led to serious fibrotic and ER stress response, Smad3 was activated by phosphorylation significantly and then was translocated into the nucleus, whereas p-Smad2 was largely unaffected in embryonic fibroblast cells. Ufbp1 overexpression obviously suppressed Smad3 phosphorylation in Hela cells. Ufbp1 was found to be in full combination with Smad3 using endogenous immunoprecipitation. Taken together, our findings suggest that downregulation or ablation of Ufbp1 leads to Smad3 activation, elevated ER stress, and hepatocyte apoptosis, which in turn causes liver fibrosis. Ufbp1 plays a protective role in ketosis-induced liver injury.

UFL1 regulates milk protein and fat synthesis-related gene expression of bovine mammary epithelial cells probably via the mTOR signaling pathway.

UFL1 is an ufmylation (a novel post-translational modification) E3 ligase, mainly located in the endoplasmic reticulum (ER), that has emerged as a significant regulator of several physiological and pathological processes. Yet its physiological function in milk synthesis in bovine mammary epithelial cells (BMECs) remains unknown. In this study, we investigated the effects of UFL1 in milk protein and fat synthesis-related gene expression, with a particular emphasis on the role of UFL1 in LPS-treated BMECs. Results showed that UFL1 depletion significantly reduced the expression of milk protein and fat synthesis-related gene and mTOR phosphorylation in both normal and LPS-treated BMECs. Overexpression of UFL1 enhanced the activation of the mTOR and milk protein and fat synthesis-related gene expression. Collectively, these above results strongly demonstrate that UFL1 could regulate milk protein and fat synthesis-related gene expression of BMECs probably via the mTOR signaling pathway.

Choline attenuates heat stress-induced oxidative injury and apoptosis in bovine mammary epithelial cells by modulating PERK/Nrf-2 signaling pathway.

Heat stress-induced decline in milk production and mammary glands dysfunction are economically important challenges facing the dairy industry, especially in summer. Choline is an organic water-soluble compound that can regulate a series of vital biological process, including cellular structural integrity and oxidative stress. However, it is unclear whether choline plays an anti-apoptosis and antioxidant effect in heat stress-induced mammary epithelial cells. This study aimed to determine the antioxidant effect of choline on heat stress-induced apoptosis and oxidative stress and its underlying molecular mechanism in bovine mammary epithelial cells (MAC-T cells). The MAC-T cells were divided into four treatment groups: control (37℃), choline (37℃), heat stress (HS, 42℃), and HS + choline. The results showed that heat stress up-regulated the HSP70 and HSP90 expression both in mRNA and protein, enhanced ROS accumulation, increased malondialdehyde (MDA) content, reduced the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, significantly increased the expression of caspase-3 and upregulated the ratio of Bax/Bcl-2 and ultimately lead to oxidative stress and apoptosis in MAC-T cells. However, choline pretreatment reversed the above phenomenon compared with the HS group. The HS + choline group inhibited heat stress-induced phosphorylation of PERK, nuclear translocation of Nrf-2 and the protein expression of GRP78. In addition, the ratio of Bax/Bcl-2 and the expression of caspase-3 were significantly reduced in HS + choline group, thereby reduced the HS-induced oxidative stress and apoptosis in MAC-T cells. In conclusion, choline attenuates heat stress-induced oxidative stress and apoptosis of MAC-T cells by modulating PERK/Nrf-2 pathway.

Sodium propionate protect the blood-milk barrier integrity, relieve lipopolysaccharide-induced inflammatory injury and cells apoptosis.

AIMS: Sodium propionate (SP) has been reported to possess an anti-inflammatory and anti-apoptotic potential by inhibiting certain signaling pathways and helps in reducing the pathological damages of the mammary gland. However, the effects of sodium propionate on attenuating Lipopolysaccharide (LPS)-induced inflammatory condition and cell damage in bovine mammary epithelial cells (bMECs) are not comprehensively studied yet. Therefore, the aim of the current investigation was to evaluate the protective effects of sodium propionate on LPS-induced inflammatory conditions and to clarify the possible underlying molecular mechanism in bMECs. MAIN METHODS: The effects of increasing doses of SP on LPS-induced inflammation, oxidative stress and apoptosis was studied in vitro. Furthermore, the underlying protective mechanisms of SP on LPS-stimulated bMECs was investigated under different experimental conditions. KEY FINDINGS: The results reveled that increased inflammatory cytokines, chemokines and those of tight junction's mRNA expression was significantly attenuated dose-dependently by propionate. Biochemical analysis revealed that propionate pretreatment modulated the LPS-induced intercellular reactive oxygen species (ROS) accumulation, oxidative and antioxidant factors and apoptosis rate. Furthermore, we investigated that the LPS activated nuclear factor-kB (NF-kB), caspase/Bax apoptotic pathways and Histone deacetylases (HDAC) was significantly attenuated by propionate in bMECs. SIGNIFICANCE: Our results suggest that sodium propionate is a potent agent for ameliorating LPS-mediated cellular disruption and limiting detrimental inflammatory responses, partly via maintaining blood milk barrier integrity, inhibiting HDAC activity and NF-kB signaling pathway.

Characterization and resistant determinants linked to mobile elements of ESBL-producing and mcr-1-positive Escherichia coli recovered from the chicken origin.

The spread of antimicrobial resistance (AMR) in Escherichia coli is a complex process linked with various mobile genetic elements (MGEs) like plasmids, transposons, and integrons. This study aimed to determine the co-occurrence of ESBL and mcr-1 and their physical linkage with MGEs in E. coli. E. coli strains of chicken origin were obtained from different commercial farms of eastern China from 2010 to 2011. Antimicrobial sensitivity testing, identification of different antibiotic-resistant genes (ARGs), and prevalence and evidence involvement of integrons, ISEcp1, ISCR1, and ISApl1, were determined. A multiplex PCR was used to detect virulence genes and the phylogenetic clustering of isolates. Conjugation experiments, plasmid replicon typing were performed to know the transferability of ARGs and MGEs. A total of 83.33% of isolates were found to be multidrug-resistant (MDR). The incidence rate of blaCTX-M, blaSHV,blaTEM, and mcr-1 was found to be 30%, 10.95%, 8.09%, and 36.66%, respectively. The most prevalent combination was noticed for mcr-1 and blaCTX-M 73%, whereas the most prominent blaCTX-M alleles found, were blaCTX-M-55 46%, followed by blaCTX-M-14 31%, and blaCTX-M-15 13%. The frequency of ISEcp1, ISCR1, ISApl1, and int1 was 27.77%, 53.70%, 51.85%, and 70.37% respectively. Most ß-lactamases, especially blaCTX-M, blaSHV, and blaTEM, were associated with ISEcp1, ISCR1, and Integron 1, whereas the ISAPl1-mcr-1 segment was observed in mcr-1-positive E. coli isolates. Phylogrouping revealed that group A was the most predominant phylotype, whereas the common virulence genes detected in these isolates were EHEC, EAEC, and EPEC. Conjugation assay also indicated that multiple genetic elements were involved; common plasmids identified were FIB 61.11%, followed by IncHI2 48.14%, and FrepB 33.33%. Propagation of such MDR strains carrying multiple resistance elements among the bacterial population is a threat of worry.

Effect of acetate, ß-hydroxybutyrate and their interaction on lipogenic gene expression, triglyceride contents and lipid droplet formation in dairy cow mammary epithelial cells.

The purpose of this study was to assess the effects of acetate and ß-hydroxybutyrate alone or in combination on lipogenic genes and their associated regulatory proteins in dairy cow mammary epithelial cells (DCMEC) using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, lipid droplet staining and a triglyceride content detection kit, to determine whether SCFA are related to milk fat synthesis regulation in DCMEC. Our experiment shows that addition of different concentrations of acetate, ß-hydroxybutyrate and their combinations to DCMEC increase in relative mRNA abundance of lipogenic genes and key transcription factors suggest an increase in lipogenic capacity, which is supported by an increased in cytosolic triglyceride content. Similarly, the protein expression level of acetyl-coenzyme A carboxylase (ACACA), fatty acid synthase (FASN) and sterol-coenzyme desaturase-1 (SCD1) genes and the transcription factor sterol regulatory element-binding protein-1 (SREBP1) were found to be increased by addition of acetate, ß-hydroxybutyrate and their combinations. The expression pattern of fat-related genes and proteins showed similar trends in almost all treatments, suggesting that common transcription factor are regulating these genes. These results show that acetate and ß-hydroxybutyrate regulate fat synthesis, further confirming that SCFAs work by targeting genes to activate the SREBP1 and insulin-induced gene 1 protein (INSIG1) signalling pathways in DCMEC.

The Importance of Nitric Oxide as the Molecular Basis of the Hydrogen Gas Fumigation-Induced Alleviation of Cd Stress on Ganoderma lucidum.

Whether or not hydrogen gas (H2) can reduce cadmium (Cd) toxicity in Ganoderma lucidum has remained largely unknown. Here, we report that Cd-induced growth inhibition in G. lucidum was significantly alleviated by H2 fumigation or hydrogen-rich water (HRW), evaluated by lower oxidative damage and Cd accumulation. Moreover, the amelioration effects of H2 fumigation were better than of HRW in an optimum concentration of H2 under our experimental conditions. Further results showed that H2-alleviated growth inhibition in G. lucidum was accompanied by increased nitric oxide (NO) level and nitrate reductase (NR) activity under Cd stress. On the other hand, the mitigation effects were reversed after removing endogenous NO with its scavenger cPTIO or inhibiting H2-induced NR activity with sodium tungstate. The role of NO in H2-alleviated growth inhibition under Cd stress was proved to be achieved through a restoration of redox balance, an increase in cysteine and proline contents, and a reduction in Cd accumulation. In summary, these results clearly revealed that NR-dependent NO might be involved in the H2-alleviated Cd toxicity in G. lucidum through rebuilding redox homeostasis, increasing cysteine and proline levels, and reducing Cd accumulation. These findings may open a new window for H2 application in Cd-stressed economically important fungi.