Site-specific pegylated IL2 mutein with biased IL2 receptor binding for cancer immunotherapy.

While Interleukin 2 (IL2) has the capability to activate both NK and T cells robustly, its limited in vivo half-life, considerable toxicity, and tendency to boost Treg cells pose significant challenges, restricting its widespread application in cancer therapy. In this investigation, we engineered a novel IL2 variant (IL2-4M-PEG) with reduced CD25 binding activity and an extended half-life by substituting amino acids associated with CD25 binding and implementing site-directed PEGylation. IL2-4M-PEG notably amplifies effector cells over Treg cells. Furthermore, our findings reveal that IL2-4M-PEG, characterized by an extended half-life, exhibits anti-tumor effects in a mouse model. Consequently, this innovative IL2 holds the potential for enhancing combined cancer therapies in the future.

Protective effect of short-chain fructo-oligosaccharides from chicory on alcohol-induced injury in GES-1 cells via Keap1/Nrf2 and NLRP3 inflammasome signaling pathways.

Numerous studies have demonstrated that polysaccharides derived from chicory possess the ability to regulate host signaling and modify mucosal damage. Yet, the effect and mechanism of short-chain fructo-oligosaccharides (scFOS) on gastric mucosa remain unclear. Hence, the protective effect of three scFOS (1-Kestose, Nystose, and 1F-Fructofuranosylnystose) against ethanol-induced injury in gastric epithelial (GES-1) cells, and the underlying molecular mechanism involved was investigated in this study. Treatment with 7% ethanol decreased the cell viability of GES-1 cells, resulting in oxidative stress and inflammation. However, pretreatment with scFOS exhibited significant improvements in cell viability, and mitigated oxidative stress and inflammation. scFOS markedly elevated the protein expression of Nrf2, HO-1, SOD1 and SOD2, while suppressing the expression of Keap1. scFOS pretreatment could also maintain mitochondrial membrane potential balance and reduce apoptosis. In addition, scFOS was observed to reduce the protein level of NLRP3, Caspase-1 and ASC. In conclusion, scFOS served a preventive function in mitigating oxidative stress and inflammation in ethanol-exposed GES-1 cells through modulation of the Keap1/Nrf2 and NLRP3 inflammasome signaling pathways. Collectively, the results indicated that scFOS could significantly mitigate ethanol-induced gastric cell damage, suggesting its potential for safeguarding gastrointestinal health.

An efficient and environmentally-friendly extraction, characterization and activity prediction of polysaccharides from Rhizoma et Radix Notopterygii.

Traditional hot water reflux extraction, ultrasonic-water extraction (UW), ultrasonic-natural deep eutectic solvent (NADES) extraction (U-NADES), ultrasonic-water and enzyme extraction (U-W-E) and ultrasonic-NADES and enzyme extraction (U-NADES-E) are employed for the extraction of Rhizoma et Radix Notopterygii polysaccharides (RNP), in which, the U-NADES-E has being proved as the most effective method. Response Surface Methodology (RSM) was utilized to optimize the conditions for U-NADES-E method. Using the optimal extraction conditions, the yield of RNP can be enhanced by nearly two-fold in comparison to the traditional extraction method, achieving a yield of 7.38 %, with a mere 30-min treatment and low ultrasonic power at 240 W. The RNP's composition included Rhamnose, Arabinose, Galactose, Glucose and Galacturonic Acid by high-performance anion-exchange chromatography. The polysaccharides from two different species of Rhizoma et Radix Notopterygii have also been characterized and identified. Network pharmacology and molecular docking predict that RNP may exert its effects in vivo through binding to PPARA, ACE and REN proteins, thereby potentially impacting diabetes outcomes. This study proposes a new, efficient, energy-saving and environmentally-friendly method for the extraction of RNP.

Phenolic acids from Chicory roots ameliorate dextran sulfate sodium-induced colitis in mice by targeting TRP signaling pathways and the gut microbiota.

BACKGROUND: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms. METHODS: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. RESULTS: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. CONCLUSION: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.

Blueberry and Blackberry Anthocyanins Ameliorate Metabolic Syndrome by Modulating Gut Microbiota and Short-Chain Fatty Acids Metabolism in High-Fat Diet-Fed C57BL/6J Mice.

In this study, blueberry (Vaccinium ssp.) anthocyanins (VA) and blackberry (Rubus L.) anthocyanins (RA) were used to investigate the effects on metabolic syndrome (MetS) and the potential mechanisms. Importantly, all of the data presented in this study were obtained from experiments conducted on mice. As a result, VA and RA reduced body weight gain and fat accumulation while improving liver damage, inflammation, glucose, and lipid metabolism induced by a high-fat diet. Moreover, VA and RA regulated the gut microbiota composition, decreasing the pro-obesity and proinflammation bacteria taxa, such as the phylum Actinobacterium and the genera Allobaculum and Bifidobacterium, and increasing those negatively associated with obesity and inflammation, such as the phylum Bacteroidetes and the genera Prevotella and Oscillospira. Additionally, the supplementation with VA and RA reversed the elevated levels of valeric, caproic, and isovaleric acids observed in the high-fat diet (HFD) group, bringing them closer to the levels observed in the Chow group. This reversal indicated that alterations in the composition and abundance of gut microbiota may contribute to the restoration of short-chain fatty acids (SCFAs) levels. Additionally, PICRUSt2 exhibited that cyanamino acid metabolism and betalain biosynthesis might be the major metabolic pathways in the HVA group compared with the HFD group, while in the HRA group, it was the phosphotransferase system. These findings suggest that VA and RA can ameliorate MetS by modulating the gut microbiota and production of SCFAs.

Serum and urine metabolomics study revealed the amelioration of Gynura bicolor extract on high fat diet-fed and streptozotocin-induced type 2 diabetic mice based on UHPLC-MS/MS.

Type 2 diabetes mellitus (T2DM) has been the most prevalent disease and has become a serious public health threat worldwide. Gynura bicolor (Willd.) DC. (GB) contains a variety of nutrients and possesses numerous activities, which might benefit those with diabetes. The current study aimed to confirm the improvement of metabolic disorders and explore the potential mechanism of GB in high fat diet-fed (HFD) and streptozotocin (STZ)-induced T2DM mice. The aboveground sample of GB was extracted with alcohol, and identified by highperformance liquid chromatography (HPLC) and liquid chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis. HFD and STZ-induced T2DM mice were administrated with GB extract. Biochemical and histopathologic examinations were conducted, and metabolomics evaluation was performed in serum and urine. GB significantly reduced body weight and liver weight, reversed hyperlipidemia, hyperglycemia, insulin resistance, oxidative stress and inflammation, improved hepatic histopathological changes and lipid deposition and mitigated liver injury in T2DM mice. Serum and urine metabolomics demonstrated a variety of significantly disturbed metabolites in T2DM and these changes were reversed after GB administration, including 13S-hydroxyoctadecadienoic acid, arachidonic acid, L-Valine and so on. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the overlapping enriched pathways in the normal control group and GB group were identified, including linoleic acid metabolism, PPAR signaling pathway, protein digestion and absorption, biosynthesis of amino acids and so on. This study demonstrates that the ethanol extract of GB remarkably attenuates metabolic disorders and maintains the dynamic balance of metabolites in T2DM, providing a scientific basis for GB in the treatment of T2DM and metabolism diseases.

One new 12, 8-guaianolide sesquiterpene lactone with antihyperglycemic activity from the roots of Cichorium intybus.

Three 12, 8-guaianolide sesquiterpene lactones, including a new compound intybusin F (1), and a new natural product cichoriolide I (2), along with six known 12, 6-guaianolide compounds (4-9) were isolated from the roots of Cichorium intybus L. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of new compounds were elucidated based on analysis of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 2, 4, 7, 8 showed significant effects on facilitating the glucose uptake in oleic acid plus high glucose-stimulated HepG2 cells at 50 µM. In addition, compounds 1, 2, 3, 6, 7 exhibited obvious inhibitory effects against NO production, of them, compounds 1, 2, 7 can significantly decrease the secretion of inflammatory cytokines (TNF-α, IL-6 and COX-2) levels in this hyperglycemic HepG2 cell model.

Gallotannin Isolated from Pericarp of Water Caltrop Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease (NAFLD) is a worldwide prevalent chronic liver disease characterized by hepatic steatosis. Water caltrop, the fruit of Trapa natan, is widely cultivated as an edible vegetable in Asian countries. In China, water caltrop pericarp has long been used as a functional food to treat metabolic syndrome, yet the bioactive substances and their pharmacological mechanisms remain unclear. In this study, a natural gallotannin, 1,2,3,6-tetra-O-galloyl-ß-D-glucopyranoside (GA), was isolated from water caltrop pericarp and evaluated for its therapeutic effect on NAFLD. Treatment of GA (15 and 30 mg/kg/day) suppressed the body weight gain (p < 0.001) and ameliorated lipid deposition (p < 0.001) in high-fat diet (HFD)-induced NAFLD mice. GA was able to alleviate HFD-induced insulin resistance (p < 0.001), oxidative stress (p < 0.001), and inflammation (p < 0.001), thereby restoring the liver function in HFD-induced NAFLD mice. Mechanistically, GA diminished the aberrant signaling pathways including AMPK/SREBP/ACC, IRs-1/Akt, IKK/IκB/NF-κB in HFD-induced NAFLD mice and modified gut microbiota dysbiosis in these mice as well. The current findings suggest that GA is a promising novel agent for NAFLD therapy.

The anion channel SLAH3 interacts with potassium channels to regulate nitrogen-potassium homeostasis and the membrane potential in Arabidopsis.

Nitrogen (N) and potassium (K) are essential macronutrients for plants. Sufficient N and K uptake from the environment is required for successful growth and development. However, how N and K influence each other at the molecular level in plants is largely unknown. In this study, we found loss-of-function mutation in SLAH3 (SLAC1 HOMOLOGUE 3), encoding a NO3- efflux channel in Arabidopsis thaliana, enhanced tolerance to high KNO3 concentrations. Surprisingly, slah3 mutants were less sensitive to high K+ but not NO3-. Addition of NO3- led to reduced phenotypic difference between wild-type and slah3 plants, suggesting SLAH3 orchestrates NO3--K+ balance. Non-invasive Micro-test Technology analysis revealed reduced NO3- efflux and enhanced K+ efflux in slah3 mutants, demonstrating that SLAH3-mediated NO3- transport and SLAH3-affected K+ flux are critical in response to high K +. Further investigation showed that two K+ efflux channels, GORK (GATED OUTWARDLY-RECTIFYING K+ CHANNEL) and SKOR (STELAR K+ OUTWARD RECTIFIER), interacted with SLAH3 and played key roles in high K+ response. The gork and skor mutants were slightly more sensitive to high K+ conditions. Less depolarization occurred in slah3 mutants and enhanced depolarization was observed in gork and skor mutants upon K+ treatment, suggesting NO3-/K+ efflux-mediated membrane potential regulation is involved in high K+ response. Electrophysiological results showed that SLAH3 partially inhibited the activities of GORK and SKOR in Xenopus laevis oocytes. This study revealed that the anion channel SLAH3 interacts with the potassium channels GORK and SKOR to modulate membrane potential by coordinating N-K balance.

Luteolin Alleviates Oxidative Stress in Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke via Modulation of the TRPV1 and CYP2A13/NRF2 Signaling Pathways.

The current study aims to investigate the therapeutic potential of luteolin (Lut), a naturally occurring flavonoid found in various medicinal plants, for treating chronic obstructive pulmonary disease (COPD) through both in vitro and in vivo studies. The results demonstrated that Lut increased body weight, reduced lung tissue swelling and lung damage indices, mitigated systemic oxidative stress levels, and decreased alveolar fusion in cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD mice. Additionally, Lut was observed to downregulate the expression of the TRPV1 and CYP2A13 proteins while upregulating SIRT6 and NRF2 protein expression in CS + LPS-induced COPD mice and cigarette smoke extract (CSE)-treated A549 cells. The concentrations of total reactive oxygen species (ROS) and mitochondrial ROS in A549 cells induced by CSE significantly increased. Moreover, CSE caused a notable elevation of intracellular Ca2+ levels in A549 cells. Importantly, Lut exhibited inhibitory effects on the inward flow of Ca2+ and attenuated the overproduction of mitochondrial and intracellular ROS in A549 cells treated with CSE. In conclusion, Lut demonstrated a protective role in alleviating oxidative stress and inflammation in CS + LPS-induced COPD mice and CSE-treated A549 cells by regulating TRPV1/SIRT6 and CYP2A13/NRF2 signaling pathways.

An integrative exploration of loquat leaf total sesquiterpene glycosides in treating insulin-resistant mice by serum and urine untargeted metabolomics analysis.

Loquat leaf is approved to be beneficial in the treatment of diabetes. Total sesquiterpene glycosides (TSG), a major chemical component cluster, has potential ability to improve insulin-resistant diabetes syndrome. Its therapeutic mechanism using metabolomics in vivo is worth to be investigated. This study aimed to reveal the underlying therapeutic mechanism of TSG on insulin-resistant mice by untargeted metabolomics, and to explore the lipid metabolism differences in vivo. High-fat diet was used to induce insulin-resistant mice model. Biochemical indicators were applied to evaluate the model validity and related treatment effect. Ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry was utilized to accomplish serum and urine untargeted metabolomics. Oral administration of TSG had a therapeutic effect on high-fat diet induced insulin-resistant mice. Four hundred forty-two metabolites in serum and 1732 metabolites in urine were annotated. Principal component analysis screened 324 differential metabolic signatures in serum sample and 1408 in urine sample. The pathway mainly involved purine metabolism and biosynthesis of unsaturated fatty acids. Lipidomic analysis of urine and serum confirmed that most lipid metabolites were fatty acyls, sterol lipids and polyketides.

Pressure pain threshold and somatosensory abnormalities in different ages and functional conditions of post-stroke elderly.

BACKGROUND: Somatosensory deficits and abnormal pain sensitivity are highly prevalent among stroke survivors, which negatively impacts their quality of life and recovery process. However, the factors for pressure pain threshold (PPT) and somatosensory abnormalities in post-stroke elderly remain unknown. The aim of this study was to explore the effects of age, side and other functional conditions, such as spasticity and motor functions, on PPT and sensory abnormalities among elderly after stroke. METHODS: The cross-sectional study finally included 43 post-stroke elderly aged over 60 and assessed the PPT of 14 bilateral muscles widely located in the whole body by using a digital force gage. Meanwhile, spasticity, motor function, joint pain and activity of daily living (ADL) were evaluated by the Modified Ashworth scale, Fugl-Meyer, and Barthel Index, respectively. All participants were divided into higher-aged and lower-aged groups based on the median age of all of them. RESULTS: Higher age tended to be associated with higher sensitivity but not significant except for one upper limb muscle, and the affected side showed significantly higher PPTs than the unaffected side in three out of seven muscles (p < 0.05). Furthermore, the somatosensory abnormalities in the affected side, particularly hypoalgesia, were more frequent in higher-aged than lower-aged patients in most assessed muscles. Meanwhile, patients with spasticity showed more increment of PPTs in affected muscles around the knee joint than patients without spasticity (p < 0.05). Patients with better motor functions, less joint pain and higher ADL performed less bilateral differences of PPTs than other patients in some muscles (p < 0.05). CONCLUSIONS: The age and side differences of mechanical pain sensitivity were found among post-stroke elderly. Older patients show higher sensitivity in both sides compared with the younger ones, and the affected side of the elder shows more somatosensory abnormalities, particularly hypoalgesia, than that of the younger ones. Post-stroke elderly in good functional conditions, such as normal muscle tone, better physical function and daily activities, and less joint pain, seems to have more equal pain sensitivity between both sides than those in poor conditions.

Sesquiterpene lactones with anti-inflammatory and cytotoxic activities from the roots of Cichorium intybus.

Cichorium intybus L. (Asteraceae), belonging to the tribe Cichorieae of the family Asteraceae, has a long history as an edible and medicinal food. Sesquiterpene lactones are commonly considered as its major active constituents. In the current study, five unreported sesquiterpene lactones, including one 12,8-guaianolide and four 12,6-guaianolides were isolated from C. intybus roots, as well as 16 known analogues. The planar structures and relative configurations of these compounds were elucidated by extensive spectroscopic analysis. The absolute configurations were determined by the time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculation method. Bioassay results showed that seven of the isolates exhibited remarkable NO production inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC50 values ranging from 1.83 to 38.81 µM. Some of them can significantly decrease the secretion of inflammatory cytokines (TNF-α and IL-6). Cytotoxicity assays demonstrated that intybusins B, as well as four known compounds, displayed obvious inhibitory activities against four human tumor cells, with IC50 values ranging from 9.01 to 27.07 µM.

Bisdemethoxycurcumin Attenuated Renal Injury via Activation of Keap1/Nrf2 Pathway in High-Fat Diet-Fed Mice.

Bisdemethoxycurcumin (BDMC), a principal and active component of edible turmeric, was previously found to have beneficial effects on metabolic diseases. Chronic kidney disease (CKD) may benefit from its potential therapeutic use. Using a high-fat diet (HFD)-fed mouse model, we examined the effects of BDMC on renal injury and tried to determine how its associated mechanism works. A number of metabolic disorders are significantly improved by BDMC, including obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia and inflammation. Further research on renal histopathology and function showed that BDMC could repair renal pathological changes and enhance renal function. Moreover, decreased serum malondialdehyde (MDA), elevated superoxide dismutase (SOD) activity, and the inhibition of renal reactive oxygen species (ROS) overproduction revealed the alleviation of oxidative stress after BDMC administration. In addition, renal Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway was activated in BDMC-treated mice. In conclusion, these findings demonstrated BDMC as a potential therapy for HFD-induced CKD via the activation of the Keap1/Nrf2 pathway.

Intra-rater and inter-rater reliability of pressure pain threshold assessment in stroke patients.

BACKGROUND: As pain is a common symptom following a stroke, pressure pain threshold (PPT) assessment can be used to evaluate pain status or pain sensitivity of patients. However, the reliability of PPT test in stroke patients is still unknown. AIM: To examine the intra- and inter-rater reliability of PPT measurements in poststroke survivors and explore their factors. DESIGN: An observational study. SETTING: The setting of the study is a rehabilitation hospital. POPULATION: The population of the study was represented by a total of 54 patients after stroke. METHODS: The study included 16 measured points on the affected and unaffected sides. PPT was assessed by two raters in turn. Intra- and inter-rater reliability was evaluated by intraclass correlation coefficients (ICC). RESULTS: All intra-rater (ICC=0.84-0.97) and inter-rater (ICC=0.83-0.95) reliability for PPT assessment were good or excellent in stroke patients. Of the 16 points, 12 showed higher intra-rater ICC values than inter-rater, whereas no evident difference was observed between the affected and unaffected sides. Furthermore, patients who were male, ischemic, or with higher motor function generally performed higher ICC values than those who were female (24 out of 32 results), hemorrhagic (28 out of 32 results), or mobility dysfunction (26 out of 32 results), respectively. CONCLUSIONS: PPT assessment with good or excellent reliability can be used in stroke patients. Neither of the two sides (affected or unaffected) affects PPT reliability, and intra-rater reliability is better than inter-rater reliability. In addition, gender, stroke type, and motor function can affect the reliability of measuring mechanical pain threshold in poststroke survivors. CLINICAL REHABILITATION IMPACT: The pressure algometer can be used as a reliable and portable tool to assess the mechanical pain tolerance and sensory function in stroke patients in clinics.

SSBP1 drives high fructose-induced glomerular podocyte ferroptosis via activating DNA-PK/p53 pathway.

High fructose consumption is a significant risking factor for glomerular podocyte injury. However, the causes of high fructose-induced glomerular podocyte injury are still unclear. In this study, we reported a novel mechanism by which high fructose induced ferroptosis, a newly form of programmed cell death, in glomerular podocyte injury. We performed quantitative proteomic analysis in glomeruli of high fructose-fed rats to identify key regulating proteins involved in glomerular injury, and found that mitochondrial single-strand DNA-binding protein 1 (SSBP1) was markedly upregulated. Depletion of SSBP1 could alleviate high fructose-induced ferroptotic cell death in podocytes. Subsequently, we found that SSBP1 positively regulated a transcription factor p53 by interacting with DNA-dependent protein kinase (DNA-PK) and p53 to drive ferroptosis in high fructose-induced podocyte injury. Mechanically, SSBP1 activated DNA-PK to induce p53 phosphorylation at serine 15 (S15) to promote the nuclear accumulation of p53, and thereby inhibited expression of ferroptosis regulator solute carrier family 7 member 11 (SLC7A11) in high fructose-exposed podocytes. Natural antioxidant pterostilbene was showed to downregulate SSBP1 and then inhibit DNA-PK/p53 pathway in its alleviation of high fructose-induced glomerular podocyte ferroptosis and injury. This study identified SSBP1 as a novel intervention target against high fructose-induced podocyte ferroptosis and suggested that the suppression of SSBP1 by pterostilbene may be a potential therapy for the treatment of podocyte ferroptosis in glomerular injury.

Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway.

As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. In vitro, the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.

Sesquiterpene glycoside isolated from loquat leaf targets gut microbiota to prevent type 2 diabetes mellitus in db/db mice.

According to ancient records, loquat leaf has been used as both a food and medicine in China for thousands of years. Sesquiterpene glycosides from loquat leaf have achieved remarkable effects on hyperglycemia. However, their specific activities and underlying mechanisms on type 2 diabetes mellitus (T2DM) are not fully understood. In the present study, we found that SG1, a unique sesquiterpene glycoside isolated from loquat leaf, had the capability to prevent insulin resistance and inflammation. In db/db mice, SG1 administration (25 and 50 mg kg-1 day-1) inhibited hyperglycemia and the release of inflammatory cytokines. To further explore the possible role of gut microbiota in SG1 for treating T2DM, we applied 16S rRNA pyrosequencing based on the V3-V4 region to analyze the fecal samples of different groups. Alpha diversity analysis showed that SG1 administration could obviously increase diversity and richness in db/db mice. At the phylum level, due to SG1 treatment, the relative abundance of Firmicutes and Actinobacteria was lowered while that of Bacteroidetes was raised. Additionally, 7 key genera in the db/db mice with SG1 supplementation were enriched: Lactobacillus, Lachnospiraceae_NK4A136_group, and Ruminococcus, Bacteroides, Prevotellaceae_UCG-001, Alistipes, and Roseburia. These findings proved that SG1 could prevent T2DM by relieving insulin resistance and inflammation and by remodeling the gut microbiota in db/db mice.

Simultaneous Determination of Five Coumarins in Peucedanum Decursivum Radix by UPLC.

OBJECTIVE: To establish an ultra-high performance liquid chromatography (UPLC) method for simultaneous determination of umbelliferonel, nodakenin, psoralen, xanthotoxin and bergapten contents in Peucedanum decursivum Radix. METHODS: The analysis was achieved on a Symmetry®C18 column (4.6 mm × 250 mm, 5 µm), with acetonitrile and water as the mobile phase in gradient elution mode. The column temperature was maintained at 30°C, with flow rate 1.0 mL·min-1. The injection volume of sample was 10 µL. The ultraviolet detection wavelength was set at the maximum absorption wavelength 325 nm for umbelliferonel and nodakenin, 259 nm for psoralen, xanthotoxin and bergapten, respectively. RESULTS: The five kinds of coumarins in Peucedanum decursivum Radix were separated well and the linear relation was obtained (R2 ≥ 0.9998). The average recoveries were 101.31, 105.27, 90.85, 106.42 and 90.19%, respectively, with Relative standard deviation (RSD) 3.07, 3.17, 1.62, 2.53 and 4.54%, respectively. CONCLUSIONS: The established method was accurate and feasible, which could be used as the basis of quality control of Peucedanum decursivum Radix.