Sodium Acetate Enhances Neutrophil Extracellular Trap Formation via Histone Acetylation Pathway in Neutrophil-like HL-60 Cells.

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis, as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16-24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, and H3K14ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

Heterotrophic nitrification processes driven by glucose and sodium acetate: New insights into microbial communities, functional genes and nitrogen metabolism from metagenomics and metabolomics.

Heterotrophic nitrification (HN) bacteria use organic carbon sources to remove ammonia nitrogen (NH4+-N); however, the mechanisms of carbon and nitrogen metabolism are unknown. To understand this mechanism, HN functional microbial communities named MG and MA were enriched with glucose and sodium acetate, respectively. The NH4+-N removal efficiencies were 98.87 % and 98.91 %, with 88.06 % and 69.77 % nitrogen assimilation for MG and MA at 22 h and 10 h, respectively. Fungi (52.86 %) were more competitive in MG, and bacteria (99.99 %) were dominant in MA. Metagenomic and metabolomic analyses indicated that HN might be a signaling molecule (NO) in the production and detoxification processes when MG metabolizes glucose (amo, hao, and nosZ were not detected). MA metabolizes sodium acetate to produce less energy and promotes nitrogen oxidation reduction; however, genes (hao, hox, and NOS2) were not detected. These results suggest that NO and energy requirements induce microbial HN.

Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids.

PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3ß in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.

Supplementation of sodium acetate improves the growth performance and intestinal health of rabbits through Wnt/ß-catenin signaling pathway.

Acetic acid, which is one of the most abundant short-chain fatty acids (SCFA) in rabbits' cecum, has been reported to play an important function during various physiological metabolic processes. The present study was conducted to elucidate the effects of sodium acetate on growth performance and intestinal health by evaluating feed intake and efficiency, diarrhea score, serum and cecum metabolites, cecal pH and SCFA, histological staining, nutritional composition of meat and gene expression profile of cecum in rabbits. As a result of sodium acetate supplement, the feed conversion ratio, diarrhea score, and diameter of muscle fiber were significantly decreased (P < 0.05). Additionally, dietary sodium acetate significantly increased in total area of muscle fibers and content of crude ash (P < 0.05). Dietary sodium acetate significantly increased serum glucose, total bile acid, and total cholesterol levels and decreased amylase, lipase, and tCO2 content (P < 0.05). Further examination suggested that sodium acetate supplementation enhanced the micro-environment of cecum, evidenced by significantly increased levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase, and decreased pH and amylase levels (P < 0.05). According to transcriptome sequencing of cecal tissues, differentially expressed genes were predominantly enriched in cell cycle, ABC transporters, and chemokine signaling pathways. Sodium acetate was further suggested to stimulate the proliferation and migration of rabbits' cecum epithelial cells by activating Wnt/ß-catenin pathway both in vivo and in vitro. In conclusion, dietary sodium acetate supplementation improved growth performance and intestinal health in rabbits.

Acetate plays a significant role in modulating production performance of animals. This study shows that sodium acetate supplementation in diet enhances rabbit growth performance by improving intestinal health and stimulating cecum epithelial cell proliferation. The supporting evidence suggests that sodium acetate significantly reduced the feed conversion ratio and diarrhea score in rabbits, while also enhancing the cecum's resistance to oxidative stress. Sodium acetate improves meat quality to some extent, as reflected in an increase total area of muscle fibers and content of crude ash. Sodium acetate was further suggested to stimulate the proliferation and migration of rabbits' cecum epithelial cells by activating Wnt/ß-catenin pathways both in vivo and in vitro. In conclusion, these findings suggest dietary sodium acetate is a useful additive for rabbit production.

Global transcriptome analysis of Pseudomonas aeruginosa NT06 response to potassium chloride, sodium lactate, sodium citrate, and microaerophilic conditions in a fish ecosystem.

Pseudomonas aeruginosa is an opportunistic pathogen that recently has been increasingly isolated from foods, especially from minimally processed fish-based products. Those are preserved by the addition of sodium chloride (NaCl) and packaging in a modified atmosphere. However, the current trends of minimizing NaCl content may result in an increased occurrence of P. aeruginosa. NaCl can be replaced with potassium chloride (KCl) or sodium salts of organic acids. Herein, we examined the antimicrobial effects of KCl, sodium lactate (NaL), sodium citrate (NaC), and sodium acetate (NaA) against P. aeruginosa NT06 isolated from fish. Transcriptome response of cells grown in medium imitating a fish product supplemented with KCl and KCl/NaL/NaC and maintained under microaerophilic conditions was analysed. Flow cytometry analysis showed that treatment with KCl and KCl/NaL/NaC resulted in changed metabolic activity of cells. In response to KCl and KCl/NaL/NaC treatment, genes related to cell maintenance, stress response, quorum sensing, virulence, efflux pump, and metabolism were differentially expressed. Collectively, our results provide an improved understanding of the response of P. aeruginosa to NaCl alternative compounds that can be implemented in fish-based products and encourage further exploration of the development of effective methods to protect foods against the P. aeruginosa, underestimate foodborne bacteria.

Sodium acetate prevents testicular damage in Wistar rats subjected to testicular ischaemia/reperfusion injury.

AIMS: The aim of this study was to investigate the potential antioxidant, anti-inflammatory, and sperm function-preserving properties of sodium acetate (ACE), a histone deacetylase (HDAC) inhibitor, in a rat model of testicular torsion/detorsion (T/D). MAIN METHODS: Littermate Wistar rats of identical weight were subjected to sham surgery or testicular T/D by rotating the left testis at 720° around its axis along the spermatic cord clockwise and fixing it in this position for two and a half hours. 1 h before detorsion, T/D + ACE-treated rats were treated with ACE (200 mg/kg/day, per os) while T/D rats were vehicle-treated by administering 0.5 mL of distilled water. After 72 h, animals were euthanized, and the left testes were harvested for bio-molecular and histological analysis. KEY FINDINGS: Acetate administration attenuated T/D-induced rises in serum and testicular HDAC and testicular xanthine oxidase, uric acid, MDA, GSSG, MPO, TNF-α, IL-1ß, IL-6, NFkB, HIF-1α, and VCAM-1. In addition, acetate treatment alleviated T/D-induced decline in sperm quality (count, motility, viability, and normal morphology) and testicular 3ß-HSD, 17ß-HSD, testosterone, GSH, GSH/GSSG, SOD, catalase, GPx, GST, Nrf2, and HO-1. Furthermore, acetate prevented T/D-distorted testicular histoarchitecture and spermatogenic germ cell loss. SIGNIFICANCE: Sodium acetate during the post-ischaemic phase of testicular T/D may be beneficial in preventing I/R injury and maintaining fertility.

Evaluating Acetate as a Renoprotective Agent After Kidney Ischemia in a Porcine Model.

Objective: Renoprotection from reperfusion injury appears to be conferred by HIF-2a activation, which can be stimulated by exogenous acetate administration. The study objective was to assess whether administration of acetate in a porcine model can mitigate kidney injury related to ischemia-reperfusion after renal hilar occlusion. Methods: A porcine single-kidney model was created by performing a laparoscopic nephrectomy followed by animal recovery. After 2 days, the animals underwent laparoscopic hilar dissection. Block randomization was used to assign pigs into one of four experimental groups. One treatment block of pigs received 150 mEq of sodium acetate intravenously during 90 minutes of en bloc occlusion of the renal hilum (herein noted as "cross-clamping"). Another block received 0.75 g/kg of oral sodium acetate for 3 days prior to cross-clamping. A third block received no acetate and underwent hilar dissection without cross-clamping (negative control). The final block received no acetate and underwent cross-clamping (positive control). Serum creatinine was used to estimate renal function post-nephrectomy. Results: A total of 16 animals (4 pigs in each group) completed the study protocol. Median pig weight was 34.6 kg. One pig receiving IV acetate was excluded from the final analysis because of unrecoverable renal failure after cross-clamping. There was a significantly lower mean serum creatinine for the IV acetate group compared with the positive control group 72 hours after cross-clamping (p = 0.012). The same effect was not observed for the pigs receiving oral acetate. By day 7, renal function had recovered without significant difference in all groups. Conclusions: We observed that the administration of intravenous acetate conferred a significant renoprotective benefit in our single kidney ischemia-reperfusion porcine model 72 hours after hilar occlusion. This work is hypothesis-generating, and further work in human subjects undergoing renal hilar occlusion during partial nephrectomy is warranted.

Acetate Alleviates Gut Microbiota Depletion-Induced Retardation of Skeletal Muscle Growth and Development in Young Mice.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously demonstrated. Acetate is the predominant short-chain fatty acids synthesized by gut microbiota through the fermentation of dietary fiber; however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during the rapid growth stage remains to be further elucidated. Herein, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on the skeletal muscle growth and development of young mice with gut microbiota deficiency. We found that the concentration of serum acetate, body mass gain, succinate dehydrogenase activity, and expression of the myogenesis maker gene of skeletal muscle in the GS group were higher than those in the GF group, following sodium acetate supplementation. Furthermore, the transcriptome analysis revealed that acetate activated the biological processes that regulate skeletal muscle growth and development in the GF group, which are otherwise inhibited due to a gut microbiota deficiency. The in vitro experiment showed that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation. Overall, our findings proved that acetate promotes skeletal muscle growth and development in young mice via increasing Gm16062 expression.

Comparative Proteome Profiling of Extracellular Vesicles from Three Growth Phases of Haematococcus pluvialis under High Light and Sodium Acetate Stresses.

Extracellular vesicles (EVs) are nano-sized particles involved in intercellular communications that intrinsically possess many attributes as a modern drug delivery platform. Haematococcus pluvialis-derived EVs (HpEVs) can be potentially exploited as a high-value-added bioproduct during astaxanthin production. The encapsulation of HpEV cargo is a crucial key for the determination of their biological functions and therapeutic potentials. However, little is known about the composition of HpEVs, limiting insights into their biological properties and application characteristics. This study examined the protein composition of HpEVs from three growth phases of H. pluvialis grown under high light (350 µmol·m-2·s-1) and sodium acetate (45 mM) stresses. A total of 2038 proteins were identified, the majority of which were associated with biological processes including signal transduction, cell proliferation, cell metabolism, and the cell response to stress. Comparative analysis indicated that H. pluvialis cells sort variant proteins into HpEVs at different physiological states. It was revealed that HpEVs from the early growth stage of H. pluvialis contain more proteins associated with cellular functions involved in primary metabolite, cell division, and cellular energy metabolism, while HpEVs from the late growth stage of H. pluvialis were enriched in proteins involved in cell wall synthesis and secondary metabolism. This is the first study to report and compare the protein composition of HpEVs from different growth stages of H. pluvialis, providing important information on the development and production of functional microalgal-derived EVs.

Sodium acetate abates lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP signaling and activating Nrf2/HO-1 in male Wistar rat.

Oxidative stress has been linked with lead toxicity, including lead-induced sexual dysfunction. On the contrary, sodium acetate has been proven to exert antioxidant activity. However, the effect of sodium acetate on lead-induced sexual dysfunction has not been fully explored. This study investigated the effect of sodium acetate on lead-induced sexual dysfunction, exploring the involvement of testosterone, eNOS/NO/cGMP, and Nrf2/HO-1 signaling. Twenty male Wistar rats with similar weights were randomly assigned into four groups (n = 5 rats/group) after two weeks of acclimatization. Animals were vehicle-treated (0.5 ml/day of distilled water, per os), acetate-treated (200 mg/kg/day, per os), lead-treated (20 mg/kg/day, per os), or lead + acetate-treated. The results revealed that sodium acetate treatment attenuated lead-induced rise in penile lead, malondialdehyde and oxidized glutathione concentrations, and acetylcholinesterase activity. In addition, lead exposure prolonged mount, intromission, and ejaculation latency and reduced mount, intromission, and ejaculation frequency, as well as the motivation to mate and penile reflex, which were improved by acetate treatment. More so, acetate treatment ameliorated lead-induced reductions in absolute and relative penile weight, eNOS, NO, cGMP, luteinizing hormone, follicle-stimulating hormone, testosterone, dopamine, Nrf2, HO-1, and reduced glutathione concentrations, as well as glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase activities. In conclusion, this study demonstrates that sodium acetate attenuated lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP and Nrf2/HO-1 signaling. Despite the compelling data presented in this study, other possible associated mechanisms in the protective role of acetate should be explored.

Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats.

Despite the effectiveness of doxorubicin (DOX) in the management of a wide range of cancers, a major challenge is its cardio-toxic effect. Oxidative stress, inflammation, and apoptosis are major pathways for the cardiotoxic effect of DOX. On the other hand, acetate reportedly exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. This particular research assessed the impact of acetate on cardiotoxicity induced by DOX. Mechanistically, acetate dramatically inhibited DOX-induced upregulation of xanthine oxidase and uric acid pathway as well as downregulation of Nrf2/HO-1 signaling and its upstream proteins (reduced glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione, and catalase, glutathione reductase). In addition, acetate markedly attenuated DOX-driven rise inTNF-α, NFkB IL-6 and IL-1ß expression, and myeloperoxidase activity. Furthermore, acetate significantly ameliorated DOX-led suppression of Bcl-2 and Ca2+-ATPase activity and upregulation of Bax, caspase 3, and caspase 9 actions. Improved body weight, heart structural integrity, and cardiac function as depicted by cardiac injury markers convoyed these cascades of events. Summarily, the present study demonstrated that acetate protects against DOX-induced cardiotoxicity by upregulating Nrf2/HO-1 signaling and downregulating NFkB-mediated activation of Bax/Bcl-2 and caspase signaling.

Roles of nanoparticles in arsenic mobility and microbial community composition in arsenic-enriched soils.

Environmental effects of nano remediation engineering of arsenic (As) pollution need to be considered. In this study, the roles of Fe2O3 and TiO2 nanoparticles (NPs) on the microbial mediated As mobilization from As contaminated soil were investigated. The addition of Fe2O3 and TiO2 NPs restrained As(V) release, and stimulated As(III) release. As(V) concentration decreased by 94% and 93% after Fe2O3 addition, and decreased by 89% and 45% after TiO2 addition compared to the Biotic and Biotic+Acetate (amended with sodium acetate) controls, respectively. The maximum values of As(III) were 20.5 and 27.1 µg/L at 48 d after Fe2O3 and TiO2 NPs addition, respectively, and were higher than that in Biotic+Acetate control (12.9 µg/L). The released As co-precipitated with Fe in soils in the presence of Fe2O3 NPs, but adsorbed on TiO2 NPs in the presence of TiO2 NPs. Moreover, the addition of NPs amended with sodium acetate as the electron donor clearly promoted As(V) reduction induced by microbes. The NPs addition changed the relative abundance of soil bacterial community, while Proteobacteria (42.8%-70.4%), Planctomycetes (2.6%-14.3%), and Firmicutes (3.5%-25.4%) were the dominant microorganisms in soils. Several potential As/Fe reducing bacteria were related to Pseudomonas, Geobacter, Desulfuromonas, and Thiobacillus. The addition of Fe2O3 and TiO2 NPs induced to the decrease of arrA gene. The results indicated that the addition of NPs had a negative impact on soil microbial population in a long term. The findings offer a relatively comprehensive assessment of Fe2O3 and TiO2 NPs effects on As mobilization and soil bacterial communities.

Acetate attenuates cyclophosphamide-induced cardiac injury via inhibition of NF-kB signaling and suppression of caspase 3-dependent apoptosis in Wistar rats.

AIM: The goal of the current study was to examine the potential therapeutic effects of sodium acetate on cardiac toxicities caused by cyclophosphamide in Wistar rats. The possible involvement of NF-kB/caspase 3 signaling was also explored. MAIN METHODS: Thirty-two male Wistar rats were divided into four groups at random. (n = 8). The control animals received 0.5 mL of distilled water orally for 14 days, the acetate-treated group received 200 mg/kg/day of sodium acetate orally for 14 consecutive days, and cyclophosphamide-treated rats received 150 mg/kg /day of cyclophosphamide i.p. on day 8, while cyclophosphamide + acetate group received sodium acetate and cyclophosphamide as earlier stated. KEY FINDINGS: Results showed that cyclophosphamide-induced cardiotoxicity, which manifested as a marked drop in body and cardiac weights as well as cardiac weight/tibial length, increased levels of troponin, C-reactive protein, lactate, and creatinine kinase, and lactate dehydrogenase activities in the plasma and cardiac tissue. Histopathological examination also revealed toxic cardiac histopathological changes. These alterations were associated with a significant increase in xanthine oxidase and myeloperoxidase activities, uric acid, malondialdehyde, TNF-α, IL-1ß, NFkB, DNA fragmentation, and caspase 3 and caspase 9 activities in addition to a marked decline in Nrf2 and GSH levels, and SOD and catalase activities in the cardiac tissue. Acetate co-administration significantly attenuated cyclophosphamide cardiotoxicity by its antioxidant effect, preventing NFkB activation and caspase 9/caspase 3 signalings. SIGNIFICANCE: This study shows that acetate co-administration may have cardio-protective effects against cyclophosphamide-induced cardiotoxicity by inhibiting NF-kB signaling and suppressing caspase-3-dependent apoptosis.

Comparative insight into the effects of different carbon source supplement on antibiotic resistance genes during whole-run and short-cut nitrification-denitrification processes.

Mature landfill leachate is known for nitrogen-removal challenging and meantime was considered as an important sink of antibiotic resistance genes (ARGs). The added external carbon sources, enabling the short-cut nitrification and denitrification, may facilitate the proliferation of bacteria that possibly carry ARGs. However, this speculation has yet to be studied. Here, we explored the effects of glucose, sodium acetate, and methanol supplements on ARGs during whole-run and short-cut treatment processes. The results showed that sodium acetate supplement during short-cut process efficiently reduced the abundances of total ARGs (0.84-1.99 copies/16S rRNA) and integrons (0.59-1.20 copies/16S rRNA), which were highly enhanced by methanol addition during whole-run treatment process (total ARGs: 3.60-11.01 copies/16S rRNA, integrons: 1.20-4.69 copies/16S rRNA). Indirect gradient analysis showed that the variation of ARGs was not correlated with the supplement of different external carbon source. Correlation analysis indicated that dominant intl1 (55.99 ± 17.61% of integrons) showed positively significant correlations with all detected ARGs expect for sul2 and ermB (p < 0.05), suggesting the significant role on ARGs dissemination. Redundancy analysis illustrated that the potential hosts of intl1, intl2, sul1, tetQ, tetM, mefA, and mexF were dominant Bacteroidetes and Actinobacteria. Interestingly, the numbers and significant extent of correlations under the supplement of sodium acetate during short-cut denitrification process were obviously declined, and it was in accordance with ARGs reduced by sodium acetate supplement, suggesting sodium acetate displayed the efficient ARGs reduction during short-cut process. In summary, this study provides a comparative understanding of the effects on ARGs by different carbon source supplements during nitrification-denitrification processes of leachate; sodium acetate is the optimal carbon source.

Ethanol Metabolite, Acetate, Increases Excitability of the Central Nucleus of Amygdala Neurons through Activation of NMDA Receptors.

The central nucleus of the amygdala (CeA) is a key brain region involved in emotional and stressor responses due to its many projections to autonomic regulatory centers. It is also a primary site of action from ethanol consumption. However, the influence of active metabolites of ethanol such as acetate on the CeA neural circuitry has yet to be elucidated. Here, we investigated the effect of acetate on CeA neurons with the axon projecting to the rostral ventrolateral medulla (CeA-RVLM), as well as quantified cytosolic calcium responses in primary neuronal cultures. Whole-cell patch-clamp recordings in brain slices containing autonomic CeA-RVLM neurons revealed a dose-dependent increase in neuronal excitability in response to acetate. N-Methyl-d-aspartate receptor (NMDAR) antagonists suppressed the acetate-induced increase in CeA-RVLM neuronal excitability and memantine suppressed the direct activation of NMDAR-dependent inward currents by acetate in brain slices. We observed that acetate increased cytosolic Ca2+ in a time-dependent manner in primary neuronal cell cultures. The acetate enhancement of calcium signaling was abolished by memantine. Computational modeling of acetic acid at NMDAR/NR1 glutamatergic and glycinergic sites suggests potential active site interactions. These findings suggest that within the CeA, acetate is excitatory at least partially through activation of NMDAR, which may underlie the impact of ethanol consumption on autonomic circuitry.

Bidirectional Regulation of Sodium Acetate on Macrophage Activity and Its Role in Lipid Metabolism of Hepatocytes.

Short-chain fatty acids (SCFAs) are important metabolites of the intestinal flora that are closely related to the development of non-alcoholic fatty liver disease (NAFLD). Moreover, studies have shown that macrophages have an important role in the progression of NAFLD and that a dose effect of sodium acetate (NaA) on the regulation of macrophage activity alleviates NAFLD; however, the exact mechanism of action remains unclear. This study aimed to assess the effect and mechanism of NaA on regulating the activity of macrophages. RAW264.7 and Kupffer cells cell lines were treated with LPS and different concentrations of NaA (0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, and 5 mM). Low doses of NaA (0.1 mM, NaA-L) significantly increased the expression of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1 beta (IL-1ß); it also increased the phosphorylation of inflammatory proteins nuclear factor-κB p65 (NF-κB p65) and c-Jun (p < 0.05), and the M1 polarization ratio of RAW264.7 or Kupffer cells. Contrary, a high concentration of NaA (2 mM, NaA-H) reduced the inflammatory responses of macrophages. Mechanistically, high doses of NaA increased intracellular acetate concentration in macrophages, while a low dose had the opposite effect, consisting of the trend of changes in regulated macrophage activity. Besides, GPR43 and/or HDACs were not involved in the regulation of macrophage activity by NaA. NaA significantly increased total intracellular cholesterol (TC), triglycerides (TG), and lipid synthesis gene expression levels in macrophages and hepatocytes at either high or low concentrations. Furthermore, NaA regulated the intracellular AMP/ATP ratio and AMPK activity, achieving a bidirectional regulation of macrophage activity, in which the PPARγ/UCP2/AMPK/iNOS/IκBα/NF-κB signaling pathway has an important role. In addition, NaA can regulate lipid accumulation in hepatocytes by NaA-driven macrophage factors through the above-mentioned mechanism. The results revealed that the mode of NaA bi-directionally regulating the macrophages further affects hepatocyte lipid accumulation.

External sodium acetate improved Cr(VI) stabilization in a Cr-spiked soil during chemical-microbial reduction processes: Insights into Cr(VI) reduction performance, microbial community and metabolic functions.

Interest combined chemical and microbial reduction for Cr(VI) remediation in contaminated sites has greatly increased. However, the effect of external carbon sources on Cr(VI) reduction during chemical-microbial reduction processes has not been studied. Therefore, in this study, the role of external sodium acetate (SA) in improving Cr(VI) reduction and stabilization in a representative Cr(VI)-spiked soils was systemically investigated. The results of batch experiments suggested that the soil Cr(VI) content declined from 1000 mg/kg to 2.6-5.1 mg/kg at 1-5 g C/kg SA supplemented within 15 days of reaction. The external addition of SA resulted in a significant increase in the relative abundances of Cr(VI)-reducing microorganisms, such as Tissierella, Proteiniclasticum and Proteiniclasticum. The relative abundance of Tissierella increased from 9.1% to 29.8% with the SA treatment at 5 g C/kg soil, which was the main contributors to microbial Cr(VI) reduction. Redundancy analysis indicated that pH and SA were the predominant factors affecting the microbial community in the SA treatments at 2 g C/kg soil and 5 g C/kg soil. Functional prediction suggested that the addition of SA had a positive effect on the metabolism of key substances involved in Cr(VI) microbial reduction. This work provides new insightful guidance on Cr(VI) remediation in contaminated soils.

Sodium acetate ameliorates cisplatin-induced kidney injury in vitro and in vivo.

Cisplatin is an effective chemotherapeutic drug against tumors. Studies often report on the improvement of kidney injury by probiotics or short-chain fatty acids (SCFAs); however, the effects of SCFAs on cisplatin-induced kidney injury are rarely studied. The aim of this study is to evaluate the function of sodium acetate on preventing cisplatin-induced kidney injury. Cell viability was detected by MTT assay. SA-ß-gal staining was performed to investigate premature senescence. Reactive oxygen species (ROS) production was analyzed by H2DCFDA staining. Propidium iodide (PI) staining was analyzed by cell cycle. Protein expression was determined by Western blot assay. Annexin Ⅴ/PI staining was used to investigate cisplatin-induced apoptosis. Tumor growth and kidney injury were evaluated in C57BL/6 mice. Sodium acetate ameliorated cisplatin-induced premature senescence and ROS production in SV40 MES-13 glomerular cells, NRK-52E renal tubular cells, and NRK-49F renal fibroblast cells. Cisplatin-induced cell cycle arrest was inhibited by sodium acetate in SV40 MES-13 and NRK-49F cells. Sodium acetate alleviated cisplatin-induced apoptosis in vivo and in vitro but not cisplatin-induced fibrosis. Our study demonstrated that sodium acetate inhibited cisplatin-induced premature senescence, cell cycle arrest, and apoptosis by attenuating ROS production. This strategy may be useful in the treatment of cisplatin-induced kidney injury.

[Effects of Nutrients on the Growth of Microcystis aeruginosa and Bacteria in the Phycosphere].

The "bacteria-algae" system plays an important role in water ecosystems. The effects of bacteria in phycospheres on the growth of Microcystis aeruginosa under in-situ nutrient stimulation were studied to explore the bacteria-algae interaction during a cyanobacteria bloom. The results showed that LB medium could inhibit the growth of M. aeruginosa, and the algicidal rate was 86.49%. Sodium acetate, glucose, and sodium citrate could promote M. aeruginosa, and the growth rate was more than 50%. The addition of nutrients in M. aeruginosa could have changed the biocoenosis in the phycosphere and increased the species richness by 16S rRNA gene sequencing, and the number of bacteria in the phycosphere increased dramatically in the LB medium and peptone groups. The physiological and biochemical responses showed that algae suffered serious lipid peroxidation, and superoxide dismutase (SOD) and catalase (CAT) activities first increased significantly and subsequently decreased under the oxidative stress of LB medium or peptone. Scanning electron microscopy (SEM) indicated that the surface of algae cells appeared wrinkled, invaded, and atrophied under LB medium stimulation, whereas bacteria in the phycosphere significantly increased. Furthermore, six strains of algicidal bacteria were isolated from the LB medium and peptone groups, and the algicidal rate of Bacillus sp. A1 was 97.55%, which confirmed that the phycosphere of M. aeruginosa included algicidal bacteria. Therefore, appropriate external nutrient stimulation can produce algicidal bacteria in situ to prevent cyanobacterial blooms.

Effects of different temperatures of carbohydrate-protein-containing drinks on gastric emptying rate after exercise in healthy young men: randomized crossover trial.

BACKGROUND: The present study examined the effects of different temperatures of carbohydrate-protein-containing drinks after exercise on the subsequent gastric emptying rate in healthy young men. METHODS: Twelve healthy young men completed two, 1-day trials in random order. In both trials, the participants completed intermittent cycling exercise for 20 min, consisting of a 120% heart rate peak for 20 s, followed by 25 W for 40 s. Participants consumed 400 mL of carbohydrate-protein-containing drink (0.85 MJ) at 4 °C (EX + 4 °C) or 60 °C (EX + 60 °C) over a 5-min period after exercise. The participants sat on a chair for 2.5 h to measure their gastric emptying rate using the 13C-sodium acetate breath test. Subjective feelings of gastrointestinal discomfort and appetite were measured using a visual analog scale. Interstitial fluid glucose levels after drinking were measured using a continuous glucose-monitoring device. RESULTS: The percentage excretion of 13CO2 tended to be higher at EX + 60 °C than at EX + 4 °C from the start of the test until 30 min after drink ingestion (5.7 ± 0.5 vs. 6.5 ± 0.4%dose/h for the EX + 4 °C and EX + 60 °C trials, respectively; effect sizes [ES] = 0.277, p = 0.065). The time of maximum 13CO2 emissions per hour (Tmax-calc) and the time of half 13CO2 emissions per hour (T1/2) did not differ between trials. Subjective gastrointestinal discomfort was lower at EX + 60 °C compared to EX + 4 °C (ES = 0.328, p = 0.041). There were no significant differences in interstitial fluid glucose levels between the different temperatures of carbohydrate-protein-containing drinks after exercise (p = 0.698). CONCLUSIONS: Consumption of warm carbohydrate-protein-containing drinks after exercise may accelerate gastric emptying in the very early phase and may reduce gastric discomfort. TRIAL REGISTRATION: University Hospital Medical Information Network, UMIN000045626. Registered on June 10, 2021.