Flavonoid extracts of Citrus aurantium L. var. amara Engl. Promote browning of white adipose tissue in high-fat diet-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.

Efficacy and safety of calcium polystyrene sulfonate in patients with hyperkalemia and stage 3-5 non-dialysis chronic kidney disease: a single-center randomized controlled trial.

OBJECTIVE: To observe the clinical efficacy and safety of the short-term administration of different doses of calcium polystyrene sulfonate in the treatment of hyperkalemia in patients with stage 3-5 non-dialysis chronic kidney disease. METHODS: A prospective, open, randomized, controlled, single-center clinical observation was conducted. In total, 107 patients were randomly assigned to receive calcium polystyrene sulfonate at 15 (group A) or 30 mg/day (group B) for 1 week. Patients were assessed on days 0, 3, and 7. RESULTS: After 3 days of treatment, the serum potassium levels in groups A and B had decreased by 0.68 ± 0.46 and 0.75 ± 0.43 mmol/L, respectively. After 7 days, the serum potassium levels in groups A and B had decreased by 0.64 ± 0.37 and 0.94 ± 0.49 mmol/L, respectively. Conversely, serum sodium, phosphorus, and calcium levels did not significantly change during the treatment period. Constipation was the most common adverse drug reaction, and no treatment-related serious adverse events were observed. CONCLUSION: Calcium polystyrene sulfonate administered at a dose of 15 or 30 g/day can rapidly reduce potassium levels in patients with stage 3-5 non-dialysis chronic kidney disease without adverse effects on sodium, phosphorus, or calcium levels.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.

Response of performance, sludge characteristics, and microbial communities of biological phosphorus removal system to salinity.

The effects of salinity on highly enriched polyphosphate- or glycogen-accumulating organisms (PAOs or GAOs) have been revealed, which is meaningful but idealized. In this study, three salinity levels (0.5%, 1.0%, and 0.75%) were sequentially adopted in a PAOs and GAOs coexisted biological phosphorus removal (BPR) reactor within 150 days. Compared to a slight decrease of phosphorus removal efficiency (PRE) under 0.5% salinity (from 96.09% to 73.68%), doubled salinity (1.0%) resulted in a lengthy recovery period and a sharp PRE decline (13.89%), and the PRE was merely kept at 27.39% even through salinity was decreased to 0.75% hereafter. Salinity was also found to stimulate more extracellular protein secretion, resulting in sludge volume index reduction (<32.87 mL/g) and particle size enlargement (222.78 µm on average). Hyphomicrobium (0.96%-1.76%) and unclassified_f_Rhodobacteraceae (4.72%-13.33%) could resist certain salinity and conduct BPR, but better salt-tolerant Candidatus_Competibacter eventually became the predominant genus (>40%).

Unexpected phosphorous removal in a Candidatus_Competibacter and Defluviicoccus dominated reactor.

Competition between polyphosphate- and glycogen-accumulating organisms (PAOs and GAOs) is problematic in the enhanced biological phosphorus removal (EBPR) process. Aiming at a high phosphorus removal efficiency (PRE), the phosphorus release amount (PRA) is considered an essential evaluating indicator. However, the correlations between PRE and PRA and the abundance of PAOs are not clear. In this study, the EBPR was established and optimized via adjusting influent carbon to phosphorus ratio (C/P). After 110-day operation, 17.67 mg/L of PRA and 75.86% of PRE simultaneously achieved with influent C/P of 40 mgCOD/mgP. As for PAOs, Candidatus_Accumulibacter and Tetrasphaera were absent, while Hypomicrobium (3.69%), Pseudofulvimonas (1.02%), and unclassified_f_Rhodobacteraceae (2.41%) were found at a low level. On the contrary, Candidatus_Competibacter and Defluviicoccus were unexpectedly enriched with high abundance (24.94% and 16.04%, respectively). These results also suggested that it was difficult to distinguish whether PAOs were enriched merely based on the variations of PRA and PRE.

Design and discovery of Novel Thiazole acetamide derivatives as anticholinesterase agent for possible role in the management of Alzheimer's.

A novel series of thiazole acetamides was synthesized in excellent yields and characterized with the aid of various spectroscopic and elemental analysis. These compounds were evaluated for in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities for possible benefit in Alzheimers disease (AD). Among the synthesized compound, 6d was identified as the most potent compound of AChE (IC50=3.14±0.16 µM) with a selectivity index (SI) of 2.94 against BuChE. These compounds were further tested for inhibition of Aß aggregation and ß-secretase, where it showed potent inhibition which confirmed its multifactorial benefits in AD. The toxicity and docking study were also carried out to exemplify the pharmacological profile of compound 6d as prospective lead molecule against AD.

Convergence of microbial assimilations of soil carbon, nitrogen, phosphorus, and sulfur in terrestrial ecosystems.

How soil microbes assimilate carbon-C, nitrogen-N, phosphorus-P, and sulfur-S is fundamental for understanding nutrient cycling in terrestrial ecosystems. We compiled a global database of C, N, P, and S concentrations in soils and microbes and developed relationships between them by using a power function model. The C:N:P:S was estimated to be 287:17:1:0.8 for soils, and 42:6:1:0.4 for microbes. We found a convergence of the relationships between elements in soils and in soil microbial biomass across C, N, P, and S. The element concentrations in soil microbial biomass follow a homeostatic regulation curve with soil element concentrations across C, N, P and S, implying a unifying mechanism of microbial assimilating soil elements. This correlation explains the well-constrained C:N:P:S stoichiometry with a slightly larger variation in soils than in microbial biomass. Meanwhile, it is estimated that the minimum requirements of soil elements for soil microbes are 0.8 mmol C Kg(-1) dry soil, 0.1 mmol N Kg(-1) dry soil, 0.1 mmol P Kg(-1) dry soil, and 0.1 mmol S Kg(-1) dry soil, respectively. These findings provide a mathematical explanation of element imbalance in soils and soil microbial biomass, and offer insights for incorporating microbial contribution to nutrient cycling into Earth system models.