NaB Group Research Articles

Expression of PGC-1α, PPAR-α and UCP1 genes, metabolic and anthropometric factors in response to sodium butyrate supplementation in patients with obesity: a triple-blind, randomized placebo-controlled clinical trial.

There is increasing evidence that gut metabolites have a role in the etiology of obesity. This study aimed to investigate the effects of sodium butyrate (NaB) supplementation on the expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1α (PGC-1α), PPAR-α, and uncoupling protein-1 (UCP-1) genes, as well as on the metabolic parameters and anthropometric indices in persons with obesity. In this triple-blind placebo-controlled randomized clinical trial, 50 individuals with obesity were randomly assigned to NaB (600 mg/day) + hypo-caloric diet or placebo group + hypo-caloric diet for 8 weeks. The study measured the participants' anthropometric characteristics, food consumption, and feelings of hunger in addition to the serum levels of metabolic indices and the mRNA expression of the PGC-1α, PPAR-α, and UCP-1 genes in peripheral blood mononuclear cells (PBMCs). PGC-1α and UCP-1 genes expression significantly increased in NaB group compared to the placebo at the endpoint. A significant decrease in weight, BMI, and waist circumference (WC) was observed in NaB group. Among the metabolic factors, NaB significantly decreased fasting blood sugar (FBS) (P = 0.04), low-density lipoprotein cholesterol (LDL-C) (P = 0.038) and increased high-density lipoprotein cholesterol (HDL-C) (P = 0.016). NaB could not significantly change serum GLP-1 level. This study unveiled NaB supplementation alone cannot have significant beneficial effects on anthropometric, and biochemical factors. NaB could affect anthropometric and metabolic risk variables associated with obesity only when prescribed, along with calorie restriction. This study was registered in the Iranian Registry of Clinical Trials ( https://en.irct.ir/trial/53968 ) on 31 January 2021 (registry number IRCT20190303042905N2).

Insights into the genetic divergence in Asiatic cotton (Gossypium arboreum L.) germplasm for fibre-quality traits

Abstract Asiatic cotton (Gossypium arboreum L.) has evolved in the Indian subcontinent and is known for its adaptability to low-input management conditions. In the present study, 300 diverse G. arboreum lines, including 100 Nandyal arboreum breeding lines (NAB), 132 Arboreum germplasm collections (AGC) and 68 long-linted arboreum genotypes (LLA), were evaluated for fibre quality to assess the diversity among them and to identify promising genotypes with desirable fibre traits. Significant variations were observed among the genotypes for the studied fibre-quality traits. Principal component analysis showed that the traits micronaire (Mic) and elongation percentage (E%) followed by upper half mean length (UHML) and bundle tenacity (tenacity) were the most significant contributors to variation. Cluster analysis based on the Euclidian distance method showed 16 clusters among 300 G. arboreum genotypes. The genotypes in cluster 4 have desirable UHML, tenacity and UI (uniformity index) traits, and cluster 12 has Mic and E% traits. Furthermore, the number of genotypes with desirable fibre-quality traits was found to be higher in the AGC group than in the LLA and NAB groups. The trait tenacity followed by the UHML showed relatively higher Shannon–Weiner diversity index values across different genotypic groups. Based on the superior performance, the genotypes PA 847, PA 809, PA 837, PA 863, NDLA 3147-2, NDLA 2974 and NDLA 3081 were found to be having desirable fibre traits. The identified promising genotypes are valuable genetic resources for improving fibre quality in G. arboreum cotton.

Supplementation of coated sodium butyrate relieved weaning stress and reshaped microbial flora in weaned lambs.

Weaning is an important period in the growth and development of lambs. Thus, effectively reducing the occurrence of weaning stress is critical for maintaining lamb production. Coated sodium butyrate has been shown to reduce inflammation, promote intestinal health, and maintain homeostasis. However, the application and potential mechanism of coated sodium butyrate in alleviating weaning stress in lambs are still unclear. To evaluate the effects of coated sodium butyrate on the growth performance, antioxidant capacity, and gut microbiota of weaned lambs, 10 weaned lambs of 21-day-old were randomly divided into two groups: the CON group (basal diet) and the NaB group (basal diet +3 g/kg of coated sodium butyrate). The trial lasted 21 days. The experimental results showed that compared to the CON group, coated sodium butyrate supplementation in the diet significantly increased the average daily weight gain and daily feed intake of lambs (p < 0.05). In addition, compared to the CON group, the addition of coated sodium butyrate also significantly decreased the serum MDA level of lambs (p < 0.05). Notably, the addition of coated sodium butyrate did not have a significant effect on the cecal microbiota, while increasing the diversity of colonic microbiota and promoting the abundance of Lachnospiraceae, Verrucomicrobiota, Akkermansia, Roseburia, and Sinobacteraceae, which are associated with the nutrient absorption of lambs (p < 0.05). These results indicate that dietary supplementation with coated sodium butyrate could promote the growth and antioxidant capacity of weaned lambs and alleviate weaning stress.

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions.

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of NTD non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate NTD non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious viral titers in the lung as potently as neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection from SARS-CoV-2 infection. For therapeutic administration of antibodies, non-nAb effector functions contributed to virus suppression and lessening of lung discoloration, but the presence of neutralization was required for optimal protection from disease. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection.

Dietary sodium butyrate positively modulated intestinal microbial community, but did not promote growth of largemouth bass (Micropterus salmoides).

This study investigated the effects of dietary sodium butyrate (NaB) on growth, serum biochemical indices, intestine histology, and gut microbiota of largemouth bass (Micropterus salmoides). A basal diet was formulated and used as the control diet (Con), and five additional diets were prepared by supplementing NaB (50%) in the basal diet at 2.0, 4.0, 8.0, 12.0, and 16.0 g/kg inclusion (NaB-2, NaB-4, NaB-8, NaB-12, and NaB-16 diets). Then, the six diets were fed to triplicate groups of largemouth bass juveniles (2.4 ± 0.1 g) for 8 weeks. NaB supplementation linearly and quadratically affected weight gain (WG) and feed intake (FI) (P < 0.05). The NaB-16 group displayed lower WG (- 6.8%) and FI than the Con group (P < 0.05), while no differences were found in WG and feed conversion ratio between the other NaB groups and Con group (P > 0.05). Serum alkaline phosphatase and lysozyme activities were higher in the NaB groups (P < 0.05), and D-lactate content was lower in the NaB-12 group (P < 0.05) than the control. Intestinal lipase activity in NaB-2, NaB-4 group, and villi width in NaB-8 group were also higher than those in the Con group (P < 0.05). Compared to the Con group, the intestinal abundances of Firmicutes and Mycoplasma were increased and the abundances of Proteobacteria, Achromobacter and Plesiomonas were decreased in NaB-4 and NaB-16 groups (P < 0.05). In conclusion, dietary NaB did not promote the growth of juvenile largemouth bass, but positively modulated the intestinal microbial community.

Effects of Non-Alcoholic Beer after Running in Three Consecutive Days on Antioxidant Enzyme Activity and Muscle Damage Biomarkers

Running recovery is challenging for several body systems and can be improved by nutritional focus. Non-alcoholic beer is a widely used post-exercise beverage for its antioxidant and energetic properties. After three consecutive days of 1 h submaximal running (80% HRmax), antioxidant enzyme activity (glutathione peroxidase [GPx], glutathione reductase [GR], catalase), lactate dehydrogenase (LDH) activity as a muscle damage blood marker, and lower limb thermographic values were determined in order to observe possible changes in 20 subjects divided into two groups: control (n = 10) and NAB (n = 10). NAB drank 10 mL/kg of non-alcoholic beer post-exercise (both groups drank water ad libitum). Non-alcoholic beer did not show statistically significant changes compared to water. Regarding the effect size, the NAB group had a medium increase in thermography values (15′Post-15′Pre) on days 1 and 2 compared to the control group; a large increase in LDH activity (both 60′Post-0′Post and 60′Post-Pre) on day 2, and a medium increase (60′Post-0′Post) on day 3; a medium decrease in GR (60′Post-Pre) on days 1 and 3; and a large (60′Post-0′Post) and medium (60′Post-Pre) decrease in GPx on day 3. These findings support the idea that non-alcoholic beer is not an appropriate recovery beverage after 1 h running for three consecutive days.

The effects of sodium butyrate (NaB) combination with soy saponin dietary supplementation on the growth parameters, intestinal performance and immune-related genes expression of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂)

Soy saponins are generally known to have negative effects on growth and the intestines of aquatic animals, and appropriate levels of sodium butyrate (NaB) may provide some mitigating effects. We investigated the effects of low and high levels of soy saponin and the protective effects of NaB (based on high level of soy saponin) on growth, serum cytokines, distal intestinal histopathology, and inflammation in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). The experiment included four groups: fishmeal group (FM, 0.00% saponin and 0.00% NaB), low saponin group (SL, 0.30% saponin and 0.00% NaB), high saponin group (SH, 1.50% saponin and 0.00% NaB) and high saponin with NaB group (SH–NaB, 1.50% saponin and 0.13% NaB). The results showed compared to FM, the final body weight (FBW) and weight gain (WG) were significantly higher and lower in SL and SH, respectively (P < 0.05). Compared to SH, the FBW and WG were significant higher in SH-NaB (P < 0.05). In the serum, compared to FM, the interferon γ (IFN-γ) and interleukin-1β (IL-1β) levels in SH were significantly increased (P < 0.05). Compared to SH, the IFN-γ level was significantly decreased in SH-NaB (P < 0.05). In the distal intestine, based on Alcian Blue-Periodic Acid-Schiff (AB-PAS) observation, the goblet cell/μm was significantly increased and decreased in the SL and SH, respectively, compared to FM. The intestinal diameter/plica height ratio in the SH was significantly higher than those in the FM, SL and SH-NaB (P < 0.05). The NO and ONOO− levels in the SH were significantly higher than that in FM and SL (P < 0.05). At the transcriptional level in the distal intestine, compared to FM, the mRNA levels of tumor necrosis factor (tnfα), il1β, interleukin-8 (il8) and ifnγ were significantly up-regulated in the SH (P < 0.05). Compared to the SH, tnfα, il8 and ifnγ were significantly down-regulated in the SH-NaB (P < 0.05). Compared to the FM, the mRNA levels of claudin3, claudin15, zo2 and zo3 were significantly up-regulated in the SL (P < 0.05). The mRNA levels of occludin, claudin3, claudin12, claudin15, zo1, zo2 and zo3 were significantly down-regulated in the SH compared to the FM (P < 0.05). Additionally, compared to the SH, the mRNA levels of occludin, claudin3, claudin12, claudin15, zo1, zo2 and zo3 were significantly up-regulated in the SH-NaB (P < 0.05). After the 7-day Vibrio parahaemolyticus challenge test, the survival was significantly higher and lower in the SL and SH, respectively, compared to FM (P < 0.05). Overall, low and high levels of soy saponins had positive and negative effects on growth, disease resistance, serum cytokines, and distal intestinal development and anti-inflammation, respectively, in hybrid grouper. NaB effectively increased disease resistance and improved distal intestinal inflammation in hybrid grouper, but the effects of NaB were mainly observed in improving distal intestinal tight junctions.

Pharmacological inhibition of histone deacetylases ameliorates cognitive impairment after intracerebral hemorrhage with epigenetic alteration in the hippocampus

ObjectivesPost-stroke cognitive impairment (PSCI) interferes with neurorehabilitation in patients with stroke. Epigenetic regulation of the hippocampus has been targeted to ameliorate cognitive function. In particular, the acetylation level of histones is modulated by exercise, a potent therapy for patients with stroke. Materials and MethodsWe examined the effects of exercise and pharmacological inhibition of histone deacetylase (HDAC) using sodium butyrate (NaB) on cognitive function and epigenetic factors in the hippocampus after intracerebral hemorrhage (ICH) to seek beneficial neuronal conditioning against PSCI. Forty rats were randomly assigned to five groups: sham, control, NaB, exercise, and NaB plus exercise groups (n=8 in each group). Except for those in the sham group, all rats underwent stereotaxic ICH surgery with a microinjection of collagenase solution. Intraperitoneal administration of NaB (300 mg/kg) and treadmill exercise (11 m/min for 30 min) were conducted for approximately 4 weeks starting 3 days post-surgery. ResultsICH reduced cognitive function, as detected by the object location test, accompanied by enhanced activity of HDACs. Although exercise did not modulate HDAC activity or cognitive function, repetitive NaB administration increased HDAC activity and ameliorated cognitive impairment induced by ICH. ConclusionsThis study suggests that pharmacological treatment with an HDAC inhibitor could potentially present an enriched epigenetic platform in the hippocampus and ameliorate PSCI for neurorehabilitation following ICH.

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.

Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis

BackgroundAlcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. MethodsIn this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. ResultsAs indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. ConclusionDietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota−gut−brain axis.

Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms.MethodsMice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro.ResultsLLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration.ConclusionsLLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.

Sodium Butyrate Ameliorates Type 2 Diabetes-Related Sarcopenia Through IL-33-Independent ILC2s/IL-13/STAT3 Signaling Pathway.

Sarcopenia has been described as a new complication of type 2 diabetes mellitus (T2DM). T2DM and sarcopenia impact each other, resulting in a variety of adverse outcomes such as frailty, disability, poor quality of life and increased mortality. Sodium butyrate (NaB) is reported to play a protective role against T2DM. The present study aimed to investigate whether NaB could ameliorate T2DM-related sarcopenia and the underlying mechanisms. The male db/db mice at 7-weeks were used as T2DM-related sarcopenia animal model with C57BL/6J mice as control. Mice were grouped according to whether they received NaB orally as follows: C57BL/6J+water group, C57BL/6J+NaB group, db/db+water group, and db/db+NaB group. Then, db/db mice receiving NaB orally were administered with inhibitors of group 2 innate lymphocytes (ILC2s), anti-CD90.2 by intraperitoneal injection divided into db/db+NaB+PBS group and db/db+NaB+anti-CD90.2 group. NaB dissolved in water at 150 mM. The skeletal muscle mass was measured by dural X-ray (DXA) test. ILC2s in spleen and skeletal muscle were evaluated by flow cytometry. The expressions of IL-33, IL-13, STAT3, P-STAT3, GATA-3 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) were assessed by ELISA or WB. The morphology of skeletal muscle fibers was assessed by immunofluorescence staining. The proportion of ILC2s and the expressions of ILC2s markers IL-13 and GATA-3 were all significantly decreased in db/db mice, and these changes were improved by NaB. NaB increased the proportion of slow-twitch fibers in gastrocnemius, thus partially reversing the reduced exercise capacity of db/db mice. The expression of slow-twitch fibers marker PGC-1α induced by NaB was increased via activation of ILC2s/IL-13/STAT3 pathway. On the other way, IL-33 was not necessary for the activation of ILC2s/IL-13/STAT3 pathway. After depletion of ILC2s by anti-CD90.2, the ameliorating effect of NaB on T2DM-related sarcopenia was partially antagonized. These results indicated that NaB could ameliorate type 2 diabetes-related sarcopenia by activating IL-33-independent ILC2s/IL-13/STAT3 signaling pathway.

The Value of Neoadjuvant Anthracycline-Based Regimens for HER2-Positive Breast Cancer: A Systematic Review and Meta-analysis Including 1366 Patients.

The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013). The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

Effect of moderate beer consumption (with and without ethanol) on osteoporosis in early postmenopausal women: Results of a pilot parallel clinical trial.

Osteoporosis is a chronic progressive bone disease characterized by low bone mineral density (BMD) and micro-architectural deterioration of bone tissue, leading to an increase in bone fragility and the risk of fractures. A well-known risk factor for bone loss is postmenopausal status. Beer may have a protective effect against osteoporosis associated with its content of silicon, polyphenols, iso-α-acids and ethanol, and its moderate consumption may therefore help to reduce bone loss in postmenopausal women. Accordingly, a 2-year controlled clinical intervention study was conducted to evaluate if a moderate daily intake of beer with (AB) or without alcohol (NAB) could have beneficial effects on bone tissue. A total of 31 postmenopausal women were assigned to three study groups: 15 were administered AB (330 mL/day) and six, NAB (660 mL/day), whereas, the 10 in the control group refrained from consuming alcohol, NAB, and hop-related products. At baseline and subsequent assessment visits, samples of plasma and urine were taken to analyze biochemical parameters, and data on medical history, diet, and exercise were collected. BMD and the trabecular bone score (TBS) were determined by dual-energy X-ray absorptiometry. Markers of bone formation (bone alkaline phosphatase [BAP] and N-propeptide of type I collagen [PINP]) and bone resorption (N-telopeptide of type I collagen [NTX] and C-telopeptide of type I collagen [CTX]) were determined annually. Bone formation markers had increased in the AB and NAB groups compared to the control after the 2-year intervention. However, the evolution of BMD and TBS did not differ among the three groups throughout the study period. Therefore, according to the findings of this pilot study, moderate beer intake does not seem to have a protective effect against bone loss in early post-menopausal women.

Sodium pentaborate pentahydrate promotes hair growth through the Wnt/β-catenin pathway and growth factors

BackgroundBoron (B) is an element involved in many physiological processes in humans and accelerates wound healing and increases angiogenesis. This study aimed to evaluate the possible effects of sodium pentaborate pentahydrate (NaB) on hair growth and reveal its effects on Wnt-1, β-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-β1 (TGF-β1) signaling pathways, which are important molecular mechanisms involved in hair growth. MethodsThirty-five Sprague-Dawley/Wistar albino rats were randomly divided into five groups: non-shaved control, shaved control, NaB 1 mg (shaved + NaB 1 mg elemental B/kg CA), NaB 2 mg (shaved + NaB 2 mg elemental B/kg CA), and NaB 4 mg (shaved + NaB 4 mg elemental B/kg CA). Hair density was measured using the trichoscopy method. Dorsal skin samples were examined histopathologically at the end of the 42nd day, and follicle count, follicle diameter, and subcutaneous tissue thickness were recorded. Wnt-1, β-catenin, PDGF, VEGF, TGF-β1, and collagen I levels were analyzed with the Western blot method. ResultsIn trichoscopy measurements, hair density increased in the NaB 4 mg group (90.9%). In histopathological examination, anagen follicles were observed to increase in the NaB 1 mg and 2 mg groups (p < 0.05). Follicle diameter increased in all NaB groups (p < 0.05). The Wnt-1, β-catenin, PDGF, VEGF, TGF-β1, and collagen I level increased in the NaB 1 mg and 2 mg groups (p < 0.05), but they were similar in the NaB 4 mg group compared to the control groups (p > 0.05). ConclusionNaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, β-catenin, VEGF, PDGF, and TGF-β1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

Anti-cancer effect of boron derivatives on small-cell lung cancer

BackgroundAnti-cancer activity of boron has been reported. Although many boron derivatives such as boric acid (BA) have been discovered to have anticancer effects, there are many boron derivatives whose anticancer effects have not yet been discovered. Some of these include sodium pentaborate pentahydrate (NaB), which has had limited research on its anticancer effects, and sodium perborate tetrahydrate (SPT), whose anticancer effect has yet to be discovered.The aim of this study was to investigate the anti-cancer effects of boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) against small-cell lung cancer (SCLC) cell line DMS-114 cells in vitro. MethodsEC50 concentrations and effects of BA, NaB, and SPT on cell survival were detected with an MTS assay. The colony-forming unit (CFU) assay was used to assess their effects on cell colony formation capability. Their effects on apoptosis were determined by an Annexin-V assay. A cell cycle analysis was performed to understand at what phase the cell cycle is arrested. Real-Time PCR (RT-PCR) was used to evaluate the mRNA levels of apoptotic, anti-apoptotic, and tumor suppressor genes. Western blotting was used to determine the protein levels of p53 and Caspase 3. ResultsThe survival rates of DMS-114 cells decreased with BA, NaB and SPT after 72 h of treatment and the EC50 concentrations ​​of DMS-114 and MRC-5 cells differed 5.5-fold in BA treatment, 5,2-fold in NaB treatment and 10-fold in SPT treatment. Colony unit numbers were decreased from 350 to 128, from 320 to 95, and from 430 to 96 in the BA, NaB, and SPT treatment groups, respectively. The apoptosis increased by 10, 19, and 42 percent after treatment with BA, NaB, and SPT for 72 h, respectively. Following 72 h of treatment with BA, NaB, and SPT, some pro-apoptotic and tumor suppressor genes were upregulated and some anti-apoptotic genes were downregulated. Cell cycle arrests were detected at the G2/M phase in the BA, and NaB treatment groups and at the Sub-G1 phase in the SPT treatment group. The protein levels of P53 and Caspase 3 increased with BA, NaB and SPT treatment for 72 h. ConclusionsBA, NaB and SPT show anti-cancer activity in the DMS-114 cell line without damaging MRC-5 cells, and some of the molecular mechanisms are involved in apoptosis and cell cycle arrest.

The Three Main SCFAs Inhibit the Inflammatory Response of A549 Cells Induced by &amp;lt;i&amp;gt;Acinetobacter baumannii&amp;lt;/i&amp;gt;

Objective: The objective is to explore the mechanism of inhibitory effect of three main SCFAs (acetate, propionate and butyrate) on inflammatory response of A549 cells. Methods: Human lung adenocarcinoma cells (A549 cells) were cultured, and were divided into normal control group (NC group), A. baumannii infection group (A. baumannii group), NF-κB inhibitor group (JSH group), A. baumannii infection + sodium acetate group (NaAc group), A. baumannii infection + sodium propionate group (NaPc group) and A. baumannii infection + sodium butyrate group (NaB group). Real-time quantitative PCR was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, IL-6, and TGF-β in A549 cells. Western blotting assay was used to determine the expression of autophagy and “pyroptosis” related proteins of NRLP3, cleaved-Caspase-1 (P20), GSDMD (P30), LC-3 and Beclin-1. At the same time, the expression of NF-κB p65 protein in nucleus and cytoplasm of A549 cells was detected. The level of reactive oxygen species in A549 cells was detected by flow cytometry. Results: Compared with A. baumannii group, the mRNA expression of NLRP3, IL-1β and IL-6 in NaAc group, NaPc group and NaB group decreased significantly, the mRNA expression of Caspase-1 in NaPc group and NaB group decreased significantly, only the mRNA expression of TGF-β in NaB group increased significantly; LC3-II expression increased significantly in NaPc group and NaB group, only Beclin-1 expression increased and GSDMD (p30) expression decreased significantly in NaB group. All three kinds of SCFAs could significantly inhibit the expression of cleaved-Caspase-1 (p20) after A. baumannii infection, but there was no significant change in the protein expression of NLRP3. Compared with NC group, the production of reactive oxygen species in A. baumannii group increased significantly at 3 h after A. baumannii infection. Compared with A. baumannii group, NaB could significantly suppress the production of reactive oxygen species induced by A. baumannii. Compared with A. baumannii group, the expression of NF-κB p65 in nucleus was significantly decreased and the expression of NF-κB p65 in cytoplasm was significantly increased after 24 h pre-incubation with NaB, NaPc and NaAc, respectively. Conclusion: A. baumannii can induce inflammatory injury of pulmonary epithelial cells, and the three major SCFAs can inhibit the activation of NLRP3 inflammasome and the release of pro-inflammatory factors through NF-κB/ROS/NLRP3 pathway, which provides a new way for clinical prevention of severe inflammatory injury caused by A. baumannii infection.

Sodium butyrate ameliorates neurotoxicity and exerts anti-inflammatory effects in high fat diet-fed mice

The prevalence of high-fat diet consumption-related disorders is increasing, and it is often associated with oxidative stress, inflammation, and dysregulation in the brain may lead to neurodegenerative diseases (NDDs). Our study aims to evaluate the neuroprotective effects of sodium butyrate (NaB) on HFD-fed mice. In this study, four-week-old male C57Bl/6NTac mice were divided into three groups; the control group, the HFD group, and the HFD + NaB group where mice received 11 mg/kg body weight of NaB with HFD. Western blotting, reverse transcription-PCR, and ELISA were used for biochemical analysis of brain specimens. We found that NaB restored bodyweight and attenuated P-53, Bcl-2-associated X protein (BAX), and caspase cascades in the brains of HFD-fed mice. In addition. NaB reduced the expressions of proinflammatory cytokines and positively modulated antioxidant biomarkers. NaB treatment upregulated the expression of the growth factor-related factors PPARγ, CREB, and BDNF in the brain tissues of HFD-fed mice. Furthermore, we found that NaB significantly ameliorated glucocorticoid receptor and NLRP3 inflammasome expression. Based on our findings, NaB suppressed apoptotic and inflammatory cytokines and enhanced the expression of endogenous antioxidants in brain tissues of HFD-fed mice. Our data strongly suggests that NaB could be utilized as an effective therapeutic agent for NDDs.

Boronic Acid Pairs for Sequential Bioconjugation.

Boronic acids can play diverse roles when applied in biological environments, and employing boronic acid structures in tandem could provide new tools for multifunctional probes. This Letter describes a pair of boronic acid functional groups, 2-nitro-arylboronic acid (NAB) and (E)-alkenylboronic acid (EAB), that enable sequential cross-coupling through stepwise nickel- and copper-catalyzed processes. The selective coupling of NAB groups enables the preparation of stapled peptides, protein-protein conjugates, and other bioconjugates.

Sodium butyrate ameliorates the impairment of synaptic plasticity by inhibiting the neuroinflammation in 5XFAD mice

Current strategies for the treatment of Alzheimer's disease (AD) focus on the pathology in the later stages of disease progression. Early microglia abnormality and β-amyloid (Aβ) deposition trigger disease development before identical symptoms emerge, which leads to poor clinical treatment effects in the later stages. In the early stage of disease progression, microglia in brains of 5XFAD mice have been activated by Aβ plaques to secrete more pro-inflammatory cytokines. In the meantime, these cytokines up-regulate Aβ via increasing the APP processing. Sodium butyrate (NaB), as one of the short chain fatty acid (SCFA) generated by gut microbiota, is the inhibitor of histone deacetylase (HDAC), which reduces the secretion of pro-inflammatory cytokines. In our experiment, 8-week-old 5XFAD mice and their litter WT mice were treated with NaB or normal saline for 2 weeks (WT + Vehicle group, WT + NaB group, AD + Vehicle group and AD + NaB group). After treatment, behavioral tests were carried out. The novel object recognition (NOR) and Morris water maze (MWM) tests demonstrated that there was no significant difference between four groups of mice. The results of long-term potentiation (LTP) and depotentiation (DEP) illustrated that the synaptic plasticity was promoted in 5XFAD mice after treatment with NaB. Compared to the AD + Vehicle group, the dendritic spines were more abundant in other groups of mice. Furthermore, the synapse-associated proteins (PSD-95, SYP, NR2B) were reduced and the pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were increased in the AD + Vehicle group. These phenomena were reversed after treatment with NaB. Moreover, our results suggested that NaB suppressed the over-activation of microglia and the accumulation of Aβ in AD mice. Altogether, all results illustrated that HDAC inhibitor NaB could ameliorate the synaptic plasticity by reducing neuroinflammation in 5XFAD mice in the early stage of the disease.