Microbial metabolite sodium butyrate enhances the anti-tumor efficacy of 5-fluorouracil against colorectal cancer by modulating PINK1/Parkin signaling and intestinal flora.

Colorectal cancer (CRC) is a prevalent global health issue, with 5-fluorouracil (5-FU) being a commonly used chemotherapeutic agent for its treatment. However, the efficacy of 5-FU is often hindered by drug tolerance. Sodium butyrate (NaB), a derivative of intestinal flora, has demonstrated anti-cancer properties both in vitro and in vivo through pro-apoptotic effects and has shown promise in improving outcomes when used in conjunction with traditional chemotherapy agents. This study seeks to evaluate the impact and potential mechanisms of NaB in combination with 5-FU on CRC. We employed a comprehensive set of assays, including CCK-8, EdU staining, Hoechst 33258 staining, flow cytometry, ROS assay, MMP assay, immunofluorescence, and mitophagy assay, to detect the effect of NaB on the biological function of CRC cells in vitro. Western blotting and immunohistochemistry were used to verify the above experimental results. The xenograft tumor model was established to evaluate the in vivo anti-CRC activity of NaB. Subsequently, 16S rRNA gene sequencing was used to analyze the intestinal flora. The findings of our study demonstrate that sodium butyrate (NaB) exerts inhibitory effects on tumor cell proliferation and promotes tumor cell apoptosis in vitro, while also impeding tumor progression in vivo through the enhancement of the mitophagy pathway. Furthermore, the combined treatment of NaB and 5-fluorouracil (5-FU) yielded superior therapeutic outcomes compared to monotherapy with either agent. Moreover, this combination therapy resulted in the specific enrichment of Bacteroides, LigiLactobacillus, butyric acid-producing bacteria, and acetic acid-producing bacteria in the intestinal microbiota. The improvement in the intestinal microbiota contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Taken together, these findings indicate that NaB, a histone acetylation inhibitor synthesized through intestinal flora fermentation, has the potential to significantly enhance the therapeutic efficacy of 5-FU in CRC treatment and improve the prognosis of CRC patients.

Sodium butyrate and rosemary herb improve growth performance, biochemical profile, immunity, and carcass traits in broiler chickens.

Background: Feed additives are products used in poultry nutrition to improve the quality of feed and the safety of food byproducts from animal origin. They are promising antibiotic alternatives for the production of broilers. Aim: This study aimed to investigate the effect of sodium butyrate (SB) and RL on growth performance, biochemical profile, immunity, and carcass traits of broilers. Methods: Five hundred-one-day-old chicks of the Hubbard breed were reared on floor pens in a privet farm, Giza. The chicks were weighed on arrival (each chick weighted 43-45 gm) and randomly assigned into five equal groups, with four replicates each (25 chicks/replicate). Group 1 was fed on a broiler diet without any additions (control). The diets of groups 2 and 3 were supplemented with 500 g/ton SB and 4 kg/ton RL, respectively. In group 4, the diet was enriched with 250 g/ton SB plus 2 kg/ton RL. Chicks in group 5 were fed on a diet fortified with 500 g/ton SB plus 4 kg/ton RL. Results: Supplementation of broiler diet with 500 g/ton SB plus 4 kg /ton RL increased body weight gain (BWG) and feed efficiency ratio (FER) of birds. It decreased serum levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol triglycerides, and malondialdehyde, but increased superoxide dismutase, catalase, and immunoglobulins, phagocytic activity, lysozyme activity, and nitric oxide concentrations. Antibody titers against the Newcastle disease virus were also elevated. Conclusion: Supplementation of broiler diet with 500 g/ton SB plus 4 kg/ton RL gives the best result regarding productive efficiency and immunity of broiler chickens.

Short-chain fatty acid levels in stools of patients with inflammatory bowel disease are lower than those in healthy subjects.

OBJECTIVE: Short-chain fatty acids (SCFAs) are produced when the microbiota in the large intestine cause fermentation of dietary carbohydrates and fibers. These fatty acids constitute the primary energy source of colon mucosa cells and have a protective effect in patients suffering from inflammatory bowel disease (IBD). This study aimed to compare the SCFA levels in the stools of patients with IBD and healthy controls. METHOD: Healthy controls and patients with IBD aged 18 and over were included in the study. Stool samples from all patients and healthy controls were collected, and stool acetic acid, propionic acid, and butyric acid levels were measured using a gas chromatography-mass spectrometry measurement method. RESULTS: In this study, 64 participants were divided into two groups: 34 were in IBD (Crohn disease and ulcerative colitis) and 30 were in healthy control group. When fecal SCFA concentrations of IBD and healthy control groups were compared, a statistically significant difference was observed between them. When the fecal SCFA concentrations of Crohn's disease and ulcerative colitis patients in the IBD group were compared, however, no statistically significant difference was observed between them. Furthermore, when the participants' diet type (carbohydrate-based, vegetable-protein-based and mixed diet) and the number of meals were compared with fecal SCFA concentrations, no statistically significant difference was observed between them. CONCLUSION: In general, fecal SCFA levels in patients with IBD were lower than those in healthy controls. Moreover, diet type and the number of meals had no effect on stool SCFA levels in patients with IBD and healthy individuals.

[Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease].

OBJECTIVE: To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate (NaB) in a mouse model of Parkinson's disease (PD) via the gut-brain axis. METHODS: Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group, PD model group, and NaB treatment group. In the latter two groups, PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) once daily for 5 consecutive days, and normal saline was injected in the control group. After modeling, the mice received daily gavage of NaB (300 mg/kg) or an equal volume of saline for 14 days. Behavioral tests were carried out to assess the changes in motor function of the mice, and Western blotting was performed to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in the striatum and nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and the tight junction proteins ZO-1, Occludin, and Claudinin the colon. HE staining was used to observe inflammatory cell infiltration in the colon of the mice. RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues, and their expressions were verified using qRT-PCR and Western blotting. RESULTS: The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH, Occludin, and Claudin and downregulated expressions of α-syn, NF-κB, TNF-α, and IL-6 (all P < 0.05). HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice. RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice (P < 0.05). CONCLUSION: NaB can improve motor dysfunction, reduce dopaminergic neuron loss in the striatum, and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Taking SCFAs produced by Lactobacillus reuteri orally reshapes gut microbiota and elicits antitumor responses.

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

Effect of feeding sodium butyrate to beef female cows during pre- and post-partum period on concentrations of glucagon-like peptides in plasma and colostrum.

The objective of this study was to evaluate the effect of feeding beef cows with sodium butyrate during the late pregnancy and early post-partum periods on concentrations of glucagon-like peptide (GLP)-1 and 2 in plasma, colostrum, and transition milk. Twelve Japanese Black female cows were fed concentrate feed without (CON; n = 6) or with (BUTY; n = 6) sodium butyrate supplementation at 1.1% of dietary dry matter from -60 d relative to the expected parturition date to 4 d after parturition. Plasma total cholesterol concentration was higher for the BUTY than for the CON (P = 0.04). In addition, plasma GLP-1 concentration was higher for the BUTY than for the CON at 3 d after calving (P < 0.05). This study showed for the first time that GLP-1 is present in the colostrum of Japanese Black cows at higher concentrations as compared to in plasma (P < 0.01). On the other hand, no treatment effect was observed for concentrations of metabolite and hormone in colostrum and transition milk. In summary, feeding beef cows with sodium butyrate during the late gestation and early post-partum period likely increases plasma GLP-1 concentrations post-partum without affecting the components of colostrum and transition milk.

ARHGAP10, Transcriptionally Regulated by Sodium Butyrate, Promotes Ferroptosis of Ovarian Cancer Cells.

BACKGROUND: Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis. METHODS: Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth in vivo, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10. RESULTS: ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells. CONCLUSIONS: Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.

Autolyzed yeast and sodium butyrate supplemented alone to diets promoted improvements in performance, intestinal health and nutrient transporter in weaned piglets.

This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-ß in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.

Synergistic Effect of Dietary Supplementation with Sodium Butyrate, ß-Glucan and Vitamins on Growth Performance, Cortisol Level, Intestinal Microbiome and Expression of Immune-Related Genes in Juvenile African Catfish (Clarias gariepinus).

The effect of dietary supplementation with sodium butyrate, ß-glucan and vitamins (A, D3, E, K, C) on breeding indicators and immune parameters of juvenile African catfish was examined. The fish were fed with unenriched (group C) and enriched feed with a variable proportion of sodium butyrate/ß-glucan, and constant content of vitamins (W1-W3). After the experiment, blood and the middle gut were collected. The microbiome of the gut was determined using Next Generation Sequencing (NGS). Liver tissue was collected for determination of expression of immune-related genes (HSP70, IL-1ß, TNFα). W2 and W3 were characterized by the most favorable values of breeding indicators (p < 0.05). The highest blood cortisol concentration was in group C (71.25 ± 10.45 ng/mL), and significantly the lowest in W1 (46.03 ± 7.01 ng/ mL) (p < 0.05). The dominance of Cetobacterium was observed in all study groups, with the largest share in W3 (65.25%) and W1 (61.44%). Gene expression showed an increased number of HSP70 genes in W1. IL-1ß and TNFα genes peaked at W3. The W3 variant turns out to be the most beneficial supplementation, due to the improvement of breeding and immunological parameters. The data obtained can be used to create a preparation for commercial use in the breeding of this species.

Protective effects of butyric acid during heat stress on the survival, immune response, histopathology, and gene expression in the hepatopancreas of juvenile pacific shrimp (L. Vannamei).

This study looked at the effects of adding butyric acid (BA) to the diets of juvenile Pacific shrimp and how it affected their response to survival, immunity, histopathological, and gene expression profiles under heat stress. The shrimp were divided into groups: a control group with no BA supplementation and groups with BA inclusion levels of 0.5 %, 1 %, 1.5 %, 2 %, and 2.5 %. Following the 8-week feeding trial period, the shrimp endured a heat stress test lasting 1 h at a temperature of 38 °C. The results showed that the control group had a lower survival rate than those given BA. Interestingly, no mortality was observed in the group receiving 1.5 % BA supplementation. Heat stress had a negative impact on the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the control group. Still, these activities were increased in shrimp fed the BA diet. Similar variations were observed in AST and ALT fluctuations among the different groups. The levels of triglycerides (TG) and cholesterol (CHO) increased with high temperatures but were reduced in shrimp-supplemented BA. The activity of an antioxidant enzyme superoxide dismutase (SOD) increased with higher BA levels (P < 0.05). Moreover, the groups supplemented with 1.5 % BA exhibited a significant reduction in malondialdehyde (MDA) content (P < 0.05), suggesting the potential antioxidant properties of BA. The histology of the shrimp's hepatopancreas showed improvements in the groups given BA. Conversely, the BA significantly down-regulated the HSPs and up-regulated MnSOD transcript level in response to heat stress. The measured parameters determine the essential dietary requirement of BA for shrimp. Based on the results, the optimal level of BA for survival, antioxidant function, and immunity for shrimp under heat stress is 1.5 %.

Hexanoic acid production and microbial community in anaerobic fermentation: Effects of inorganic carbon addition.

Carbon dioxide (CO2) plays a crucial role in carbon chain elongation with ethanol serving as an electron donor. In this study, the impacts of various carbonates on CO2 concentration, hexanoic acid production, and microbial communities during ethanol-butyric acid fermentation were explored. The results showed that the addition of MgCO3 provided sustained inorganic carbon and facilitated interspecific electron transfer, thereby increasing hexanoic acid yield by 58%. MgCO3 and NH4HCO3 inhibited the excessive ethanol oxidation and decreased the yield of acetic acid by 51% and 42%, respectively. The yields of hexanoic acid and acetic acid in the CaCO3 group increased by 19% and 15%, respectively. The NaHCO3 group exhibited high headspace CO2 concentration, promoting acetogenic bacteria enrichment while reducing the abundance of Clostridium_sensu_stricto_12. The batch addition of NaHCO3 accelerated the synthesis of hexanoic acid and increased its production by 26%. The relative abundance of Clostridium_sensus_stricto_12 was positively correlated with hexanoic acid production.

Synthesis of Isoamyl Fatty Acid Ester, a Flavor Compound, by Immobilized Rhodococcus Cutinase.

Isoamyl fatty acid esters (IAFEs) are widely used as fruity flavor compounds in the food industry. In this study, various IAFEs were synthesized from isoamyl alcohol and various fatty acids using a cutinase enzyme (Rcut) derived from Rhodococcus bacteria. Rcut was immobilized on methacrylate divinylbenzene beads and used to synthesize isoamyl acetate, butyrate, hexanoate, octanoate, and decanoate. Among them, Rcut synthesized isoamyl butyrate (IAB) most efficiently. Docking model studies showed that butyric acid was the most suitable substrate in terms of binding energy and distance from the active site serine (Ser114) γ-oxygen. Up to 250 mM of IAB was synthesized by adjusting reaction conditions such as substrate concentration, reaction temperature, and reaction time. When the enzyme reaction was performed by reusing the immobilized enzyme, the enzyme activity was maintained at least six times. These results demonstrate that the immobilized Rcut enzyme can be used in the food industry to synthesize a variety of fruity flavor compounds, including IAB.

Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy.

More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.

[Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy]. / ç‰›å¥¶è›‹ç™½è¿‡æ•å©´å„¿è‚ é“èŒç¾¤ç‰¹å¼‚æ€§å˜åŒ–åŠçŸ­é“¾è„‚è‚ªé ¸æ°´å¹³åˆ†æž.

OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.

Vitamin B5 supplementation enhances intestinal development and alters microbes in weaned piglets.

This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.

Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration­resistant prostate cancer cells.

Cancer cells are characterized by increased glycolysis, known as the Warburg effect, which leads to increased production of cytotoxic methylglyoxal (MGO) and apoptotic cell death. Cancer cells often activate the protective nuclear factor erythroid 2­related factor2 (Nrf2)/glyoxalase1 (Glo1) system to detoxify MGO. The effects of sodium butyrate (NaB), a product of gut microbiota, on Nrf2/Glos/MGO pathway and the underlying mechanisms in prostate cancer (PCa) cells were investigated in the present study. Treatment with NaB induced the cell death and reduced the proliferation of PCa cells (DU145 and LNCap). Moreover, the protein kinase RNA-like endoplasmic reticulum kinase/Nrf2/Glo1 pathway was greatly inhibited by NaB, thereby accumulating MGO-derived adduct hydroimidazolone (MG-H1). In response to a high amount of MGO, the expression of Nrf2 and Glo1 was attenuated, coinciding with an increased cellular death. NaB also markedly inhibited the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (Stat3) pathway. Conversely, co­treatment with Colivelin, a Stat3 activator, significantly reversed the effects of NaB on Glo1 expression, MG-H1 production, and the cell migration and viability. As expected, overexpression of Stat3 or Glo1 reduced NaB­induced cell death. The activation of calcium/calmodulin dependent protein kinase II gamma and reactive oxygen species production also contributed to the anticancer effect of NaB. The present study, for the first time, demonstrated that NaB greatly increases MGO production through suppression of the JAK2/Stat3/Nrf2/Glo1 pathway in DU145 cells, a cell line mimicking castration­resistant PCa (CRPC), suggesting that NaB may be a potential agent for PCa therapy.

Applicability of sodium butyrate preparations from a surgeon's and gastroenterologist's perspective.

In recent years, much has been written about the possibilities of using exogenous sodium butyrate in the prevention and treatment of gastrointestinal diseases, in prehabilitation, in peri- and postoperative treatment, as well as its local application. It became possible thanks to the development of a special formulation (microencapsulation technique) enabling the delivery of unstable butyrate compounds to the large intestine, where it is used primarily as a source of energy. It also plays a key role in maintaining body homeostasis by maintaining the integrity of the intestinal epithelium and stimulating the intestinal immune system. There is growing evidence of the effectiveness of sodium butyrate in various areas of health. The following article discusses the possibilities of using microencapsulated sodium butyrate in the prevention and treatment of gastrointestinal diseases from the perspective of a gastroenterologist and gastrointestinal surgeon.

Effect of pH on the solubility and volumetric change of ready-to-use Bio-C Repair bioceramic material.

Acidic pH can modify the properties of repair cements. In this study, volumetric change and solubility of the ready-to-use bioceramic repair cement Bio-C Repair (BCR, Angelus, Londrina, PR, Brazil) were evaluated after immersion in phosphate-buffered saline (PBS) (pH 7.0) or butyric acid (pH 4.5). Solubility was determined by the difference in initial and final mass using polyethylene tubes measuring 4 mm high and 6.70 mm in internal diameter that were filled with BCR and immersed in 7.5 mL of PBS or butyric acid for 7 days. The volumetric change was established by using bovine dentin tubes measuring 4 mm long with an internal diameter of 1.5 mm. The dentin tubes were filled with BCR at 37°C for 24 hours. Scanning was performed with micro-computed tomography (micro-CT; SkyScan 1176, Bruker, Kontich, Belgium) with a voxel size of 8.74 µm. Then, the specimens were immersed in 1.5 mL of PBS or butyric acid at and 37 °C for 7 days. After this period, a new micro-CT scan was performed. Bio-C Repair showed greater mass loss after immersion in butyric acid when compared with immersion in PBS (p<0.05). Bio-C Repair showed volumetric loss after immersion in butyric acid and increase in volume after immersion in PBS (p<0.05). The acidic pH influenced the solubility and dimensional stability of the Bio-C Repair bioceramic cement, promoting a higher percentage of solubility and decrease in volumetric values.

Lacticaseibacillus rhamnosus HF01 fermented yogurt alleviated high-fat diet-induced obesity and hepatic steatosis via the gut microbiota-butyric acid-hepatic lipid metabolism axis.

The objective of this study was to investigate the anti-obesity effects and underlying mechanism of Lacticaseibacillus rhamnosus HF01 fermented yogurt (HF01-Y). Herein, obesity was induced in mice through a high-fat diet and the changes in the gut microbiota were evaluated using 16S rRNA gene sequencing, combined with the expression levels of the liver AMPK signaling pathway to analyze the potential relationship between HF01-Y-mediated gut microbiota and obesity. The results showed that supplementation with HF01-Y improved obesity-related phenotypes in mice, including reduced body weight, improved serum lipid profiles, and decreased hepatic lipid droplet formation. In addition, HF01-Y altered the composition of the gut microbiota in obese mice, significantly upregulated norank_f__Muribaculaceae, unclassified_c__Clostridia, Blautia, unclassified_o__Bacteroidales, and Rikenellaceae_RC9_gut_group, while downregulating unclassified_f__Desulfovibrionaceae, Colidextribacter, and unclassified_f__Oscillospiraceae. These alterations led to an increase of the cecum butyric acid content, which in turn indirectly promoted the activation of the AMPK signaling pathway, subsequently, inhibited fat synthesis, and promoted fatty acid oxidation related gene expression. Therefore, HF01-Y was likely to alleviate hepatic fat and relieve obesity by modulating the gut microbiota-butyric acid-hepatic lipid metabolism axis, ultimately promoting host health.

[Relationship between short-chain fatty acids in the gingival crevicular fluid and periodontitis of stage â ¢ or â £].

OBJECTIVE: To analyze the concentration of formic acid, propionic acid and butyric acid in gingival crevicular fluid (GCF) of patients with stages Ⅲ and Ⅳ periodontitis, and their relationship with periodontitis. METHODS: The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology, Peking University School and Hospital of Stomatology from February 2008 to May 2011. Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant. Periodontal clinical parameters, including plaque index(PLI), probing depth(PD), bleeding index(BI), and attachment loss(AL). Concentrations of formic acid, propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capillary electrophoresis (HPCE). The prediction ability of formic acid, propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed. RESULTS: In this study, 32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled, including 9 patients with grade B and 28 patients with grade C. Clinical periodontal variables in the patients with periodontitis were significantly higher than those in the control group (P<0.001). Formic acid was significantly lower in periodontitis than that in the control group [5.37 (3.39, 8.49) mmol/L vs. 12.29 (8.35, 16.57) mmol/L, P<0.001]. Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group: Propionic acid, 10.23 (4.28, 14.90) mmol/L vs. 2.71 (0.00, 4.25) mmol/L, P < 0.001; butyric acid, 2.63 (0.47, 3.81) mmol/L vs. 0.00 (0.00, 0.24) mmol/L, P<0.001. There was no significant difference in formic acid, propionic acid and butyric acid concentrations between grade B and grade C periodontitis (P>0.05). Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket, while the concentration of formic acid decreased with the increase of PD. Propionic acid (OR=1.51, 95%CI: 1.29-1.75) and butyric acid (OR=3.72, 95%CI: 1.93-7.17) were risk factors for periodontitis, while formic acid (OR=0.87, 95%CI: 0.81-0.93) might be a protective factor for periodontitis. Propionic acid (AUC=0.852, 95%CI: 0.805－0.900), butyric acid (AUC=0.889, 95%CI: 0.841－0.937), f (formic acid, AUC=0.844, 95%CI: 0.793－0.895) demonstrated a good predictive capacity for the risk of periodontitis. CONCLUSION: The concentration of formic acid decrease in the GCF of periodontitis patients, which is a protective factor for periodontitis, its reciprocal have good predictive capacity. However, propionic acid and butyric acid increase, which are risk factors for periodontitis and have good predictive capacity. The concentration of formic acid, propionic acid, and butyric acid vary with probing depth, but there is no significant difference between grade B and grade C periodontitis.