Understanding Hyperuricemia: Pathogenesis, Potential Therapeutic Role of Bioactive Peptides, and Assessing Bioactive Peptide Advantages and Challenges.

Hyperuricemia is a medical condition characterized by an elevated level of serum uric acid, closely associated with other metabolic disorders, and its global incidence rate is increasing. Increased synthesis or decreased excretion of uric acid can lead to hyperuricemia. Protein peptides from various food sources have demonstrated potential in treating hyperuricemia, including marine organisms, ovalbumin, milk, nuts, rice, legumes, mushrooms, and protein-rich processing by-products. Through in vitro experiments and the establishment of cell or animal models, it has been proven that these peptides exhibit anti-hyperuricemia biological activities by inhibiting xanthine oxidase activity, downregulating key enzymes in purine metabolism, regulating the expression level of uric acid transporters, and restoring the composition of the intestinal flora. Protein peptides derived from food offer advantages such as a wide range of sources, significant therapeutic benefits, and minimal adverse effects. However, they also face challenges in terms of commercialization. The findings of this review contribute to a better understanding of hyperuricemia and peptides with hyperuricemia-alleviating activity. Furthermore, they provide a theoretical reference for developing new functional foods suitable for individuals with hyperuricemia.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Metabolomics reveals the role of Lactobacillus plantarum SHY130 in hepatic metabolic regulation in a mouse model of type 2 diabetes.

BACKGROUND: Among type 2 diabetes (T2D) patients, the incidence rate of liver metabolic disorders is much higher than that in healthy subjects. It was observed in our previous research that diabetic symptoms were improved by Lactobacillus plantarum SHY130 (LPSHY130) isolated from yak yogurt in a murine model of T2D. This study sought to investigate the LPSHY130-mediated hepatic metabolic regulation in a murine model of T2D. RESULTS: Treatment with LPSHY130 improved liver function and pathological damage in diabetic mice. Untargeted metabolome analysis revealed that T2D-induced changes in 11 metabolites were regulated after LPSHY130 treatment, mainly involving purine metabolism, amino acid metabolism, and choline metabolism and pantothenate and coenzyme A biosynthesis pathways. In addition, correlation analysis indicated that hepatic metabolic changes can be adjusted by the intestinal microbiota. CONCLUSION: Overall, this study suggests that treatment with LPSHY130 relieves liver injury and regulates liver metabolism in a murine model of T2D, thus providing a theoretical basis for the use of probiotics as dietary supplements to regulate hepatic metabolic disorders associated with T2D. © 2023 Society of Chemical Industry.

Preoperative prediction of residual back pain after vertebral augmentation for osteoporotic vertebral compression fractures: Initial application of a radiomics score based nomogram.

Background: Most patients with osteoporotic vertebral compression fracture (OVCF) obtain pain relief after vertebral augmentation, but some will experience residual back pain (RBP) after surgery. Although several risk factors of RBP have been reported, it is still difficult to estimate the risk of RBP preoperatively. Radiomics is helpful for disease diagnosis and outcome prediction by establishing complementary relationships between human-recognizable and computer-extracted features. However, musculoskeletal radiomics investigations are less frequently reported. Objective: This study aims to establish a radiomics score (rad-score) based nomogram for the preoperative prediction of RBP in OVCF patients. Methods: The training cohort of 731 OVCF patients was used for nomogram development, and the validation cohort was utilized for performance test. RBP was determined as the score of visual analogue scale ≥ 4 at both 3 and 30 days following surgery. After normalization, the RBP-related radiomics features were selected to create rad-scores. These rad-scores, along with the RBP predictors initially identified by univariate analyses, were included in the multivariate analysis to establish a nomogram for the assessment of the RBP risk in OVCF patients preoperatively. Results: A total of 81 patients (11.2%) developed RBP postoperatively. We finally selected 8 radiomics features from 1316 features extracted from each segmented image to determine the rad-score. Multivariate analysis revealed that the rad-score plus bone mineral density, intravertebral cleft, and thoracolumbar fascia injury were independent factors of RBP. Our nomograms based on these factors demonstrated good discrimination, calibration, and clinical utility in both training and validation cohorts. Furthermore, it achieved better performance than the rad-score itself, as well as the nomogram only incorporating regular features. Conclusion: We developed and validated a nomogram incorporating the rad-score and regular features for preoperative prediction of the RBP risk in OVCF patients, which contributed to improved surgical outcomes and patient satisfaction.

Direct-Contact Low-Frequency Ultrasound and Pulse Lavage Eradicates Biofilms on Implant Materials In Vitro.

Pulse lavage (PL) debridement and ultrasound are both known to be the treatment of biofilm-related periprosthetic joint infection (PJI). However, the efficacy of these in combination is unknown in eradicating biofilm from the orthopaedic metal implant surface. This study was conducted to understand the efficacy of PL and ultrasound in combination in eradicating bacterial biofilms on titanium alloy in vitro. Biofilms of Staphylococcus aureus strains were grown on titanium alloy coupons for 24 h. Then, the coupons were taken to each treatment group: (i) debrided with PL, (ii) exposed to ultrasound, or (iii) exposed to both. An untreated biofilm was set as a control group. Viable plate count and confocal microscopy using live/dead staining was used to measure the amount of biofilm. Viable plate count showed an approximate two-log reduction in CFU/cm2 in PL alone, from an initial cell count on the mental surface of approximately 109 CFU/cm2. The ultrasound caused an approximate seven-log reduction, and the combination group eradicated viable biofilm bacteria completely. Confocal imaging corroborated the CFU data. Our results indicate that PL and ultrasound both are remarkably in eradicating biofilm, and the combination of PL and ultrasound is more effective than alone in reducing biofilm.

Ginsenoside Rg3 attenuates ovariectomy-induced osteoporosis via AMPK/mTOR signaling pathway.

Ginsenoside Rg3, a ginsenoside isolated from Panax ginseng, can regulate autophagy via AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. AMPK/mTOR signaling and autophagy have been reported to be involved in osteogenesis. Here, the effect of Rg3 on ovariectomy (OVX)-induced osteoporosis is explored. In vivo, rats were treated with 20 mg/kg Rg3 after OVX and the body weight (BW) was monitored. Bone mineral density (BMD), hematoxylin-eosin staining of femur tissues, osteogenesis, autophagy, and AMPK/mTOR signaling were analyzed. In vitro, MC3T3-E1 cells were treated with 0, 1, 5, 10, 20, and 100 µmol/L Rg3. 10 and 20 µmol/L Rg3, which had no significant effect on cell viability and significantly affected AMPK/mTOR signaling, were chosen for further analysis. Then osteogenic differentiation was induced with Rg3 or/and AMPK inhibitor (Compound C). AMPK/mTOR signaling, autophagy, osteogenic differentiation, and mineralization by Alizarin Red staining were analyzed. The expression or activity of AMPK/mTOR signaling-related proteins, autophagy markers, and osteogenesis markers was measured by western blotting or commercial kits, and cell viability by cell counting kit-8 assay kits. Rg3 significantly alleviated OVX-induced BW increases, BMD declines and histological changes of femur tissues, promoted osteogenesis, autophagy, and AMPK signaling, but inhibited mTOR signaling in vivo. Moreover, Rg3 significantly enhanced AMPK signaling, autophagy, osteogenic differentiation, and mineralization, but suppressed mTOR signaling in vitro. However, Compound C significantly reversed Rg3-induced alterations in vitro, indicating that Rg3 regulated autophagy, osteogenic differentiation, and mineralization via AMPK/mTOR signaling. Hence, it was speculated that Rg3 might attenuate OVX-induced osteoporosis via AMPK/mTOR signaling pathway.

Antihyperglycemic and antihyperlipidemic activities of a polysaccharide from Physalis pubescens L. in streptozotocin (STZ)-induced diabetic mice.

In this study, a polysaccharide was extracted from Physalis pubescens L. (named PP). Its antihyperglycemic and antihyperlipidemic activities were evaluated in STZ-induced diabetic mice. Results showed that PP was determined to be composed of rhamnose (Rha), arabinose (Ara), fucose (Fuc), xylose (Xyl), mannose (Man), glucose (Glc) and galactose (Gal) with molar percentages of 4.65%, 17.34%, 1.43%, 6.24%, 5.52%, 45.5%, and 19.31%, respectively. The average molecular weight (Mw) was found to be 20.0 kDa. It had a strong α-glucosidase inhibitory activity in vitro. PP treatment could enhance the oral glucose tolerance, and increase the levels of SOD, GSH, CAT, vitamin C, vitamin E, HDL-c, C-peptide, GCK and hepatic glycogen in diabetic mice. Besides, PP treatment could also decrease the levels of MDA, TG, TC, LDL-c, BUN and G-6-Pase. The regulating effects were stronger in high dose PP treatment than those in the low and medium dose treatments. In short, PP played an important role in protecting STZ-induced diabetic mice, and the effect was closely related to its activities in antioxidation and regulating glucose and lipid metabolism.

Characterization and Therapeutic Application of Mesenchymal Stem Cells with Neuromesodermal Origin from Human Pluripotent Stem Cells.

Rationale: Mesenchymal stem cells (MSC) hold great promise in the treatment of various diseases including autoimmune diseases, inflammatory diseases, etc., due to their pleiotropic properties. However, largely incongruent data were obtained from different MSC-based clinical trials, which may be partially due to functional heterogeneity among MSC. Here, we attempt to derive homogeneous mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells (hPSC) and evaluate their functional properties. Methods: Growth factors and/or small molecules were used for the differentiation of human pluripotent stem cells (hPSC) into neuromesodermal progenitors (NMP), which were then cultured in animal component-free and serum-free induction medium for the derivation and long-term expansion of MSC. The resulted NMP-MSC were detailed characterized by analyzing their surface marker expression, proliferation, migration, multipotency, immunomodulatory activity and global gene expression profile. Moreover, the in vivo therapeutic potential of NMP-MSC was detected in a mouse model of contact hypersensitivity (CHS). Results: We demonstrate that NMP-MSC express posterior HOX genes and exhibit characteristics similar to those of bone marrow MSC (BMSC), and NMP-MSC derived from different hPSC lines show high level of similarity in global gene expression profiles. More importantly, NMP-MSC display much stronger immunomodulatory activity than BMSC in vitro and in vivo, as revealed by decreased inflammatory cell infiltration and diminished production of pro-inflammatory cytokines in inflamed tissue of CHS models. Conclusion: Our results identify NMP as a new source of MSC and suggest that functional and homogeneous NMP-MSC could serve as a candidate for MSC-based therapies.

Comparison and screening of bioactive phenolic compounds in different blueberry cultivars: Evaluation of anti-oxidation and α-glucosidase inhibition effect.

This study was aimed to investigate antioxidation and α-glucosidase inhibition of the bioactive compounds in three cultivars of blueberry ('Northland' (NL) from the hybrid blueberry (V. corymbosum L.×V. angustifolium Aiton), 'Britewell' (BW), and 'Gardenblue' (GB) from the rabbiteye blueberry (Vaccinium ashei Reade)). A total of eighteen anthocyanins were identified and quantified in Anthocyanins (ACNs), among which four acylated anthocyanins were exclusively found in Northland. The blueberry anthocyanin extracts (BAEs) were further measured the antioxidant activity and α-glucosidase inhibition effect. Northland BAEs exhibited significantly superior antioxidant activity compared with BAEs of other cultivars, and the antioxidant activity was correlated with the content of anthocyanins. However, α-glucosidase inhibition test showed that Britewell BAEs had the strongest inhibitory effect. BAEs were further separated into anthocyanin fraction (AF) and copigment fraction (CF). Fifteen phenolic acids and four iridoids were identified in CF. In terms of α-glucosidase inhibition effects, the CF from three cultivars could inhibit α-glucosidase in a dose-dependent manner, while the AF did not show significant inhibitory effects. The blueberry exhibits excellent antioxidant activity and α-glucosidase inhibition.

Rapid identification of bile acids in snake bile using ultrahigh-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

Snake bile, a precious traditional Chinese medicine (TCM), was used as the major ingredient of some Chinese patent drugs, such as Shedan Chuanbei powder and Shedan Chenpi powder for hundred years. However, there is still requirement for the comprehensive and definite composition of bile acids in snake bile. In order to rapidly identify the bile acids constituents in snake bile to avoid the adulteration, ultrahigh-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS/MS) has been applied to conduct a qualitative analysis on snake bile acids. ESI ion source was used for mass spectra, and data were collected in both positive and negative ion mode. 16 kinds of reference standards, attributed to free bile acids, taurine- and glycine- conjugated bile acids, were detected and their MS behaviors were summarized. In negative ion mode, the diagnostic ions of free bile acids were obtained via the neutral losses of H2O and CO2 molecules; the diagnostic ions of taurine-conjugated bile acids were at m/z 124.0068 ([C2H6NO3S]-), m/z 106.9803 ([C2H3O3S]-) and m/z 79.9568 ([SO3]-); the diagnostic ion of glycine-conjugated bile acids was at m/z 74.0242 ([C2H4NO2]-). In positive ion mode, dehydration ions, amide bond cleavage ions, and reversed Diels-Alder at A-ring ions were detected in every kind of reference. These reference MS behaviors were used for identifying bile acids without reference standards in snake bile. As a result, totally 15 compounds, including 4 pairs of isomers, were identified by comparing the retention time, exact molecular mass and fragmentation behaviors with reference standards, respectively. Tauro-3ß,7α,12α-trihydroxy-5ß-cholenoic acid, Tauro-△8-3ß,7α,12α- trihydroxy-5ß-cholenoic acid, Tauro-3α,7α,12α,23R-tetrahydroxy-5ß-cholenoic acid, and Tauro-3α,7α-dihydroxy-12-oxo-5ß-cholenoic acid, Taurocholic acid, Glycocholic acid, Taurochenodeoxycholic acid, Taurodeoxycholic acid and Cholic acid were detected as the common bile acids in snake bile. Tauro-△8-3ß,7α,12α-trihydroxy-5ß-cholenoic acid, Tauro-3α,7α,9α,16α-tetrahydroxy-5ß-cholenoic acid, Tauro-3α,12α,17R,22R-tetrahydroxy-5ß-cholenoic acid, and Tauro-△1,8-3ß,7ß,12α-trihydroxy-5ß-cholenoic acid were firstly reported in this study.

Comparison of the effects of pretreatment with repeated electroacupuncture at GV20 and ST36 on fatigue in rats.

OBJECTIVE: To investigate and compare the effects of electroacupuncture (EA) pretreatment at GV20 and ST36 on fatigue in rats. METHODS: Rats were randomly allocated into 4 groups: control, fatigue, fatigue+GV20 and fatigue+ST36. The last two groups received EA pretreatment at GV20 or ST36 for 5 days before being maintained in cages filled with water to a height of 1.5 cm to establish an animal model of fatigue. We used the weight-loaded forced swimming test and open-field test and measured 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratios and serum levels of blood urea nitrogen (BUN), lactic dehydrogenase (LDH) and testosterone as behavioural and biochemical markers of fatigue in the rats. RESULTS: Compared with controls, rats in the (untreated) fatigue group exhibited reduced weight-loaded swimming times and total movement/distance in the open-field test, plus higher BUN/LDH and lower testosterone levels. Both EA pretreatment at GV20 and ST36 increased swimming times, and reduced serum BUN/LDH. EA pretreatment at GV20 (but not ST36) increased serum testosterone. The 5-HIAA/5-HT ratios in four brain regions were decreased in the fatigue+GV20 group compared with the fatigue group (p<0.05). By contrast, 5-HIAA/5-HT ratios in striatum and hypothalamus (but not hippocampus or midbrain) were decreased in the fatigue+ST36 group compared with the fatigue group (p<0.05). Furthermore, only pretreatment at GV20 affected the results of the open-field test. CONCLUSIONS: These results suggest that EA pretreatment had a positive effect on the prevention of fatigue. Pretreatment at GV20 had a greater anti-fatigue effect than pretreatment at ST36.

Early Holocene chicken domestication in northern China.

Chickens represent by far the most important poultry species, yet the number, locations, and timings of their domestication have remained controversial for more than a century. Here we report ancient mitochondrial DNA sequences from the earliest archaeological chicken bones from China, dating back to ∼ 10,000 B.P. The results clearly show that all investigated bones, including the oldest from the Nanzhuangtou site, are derived from the genus Gallus, rather than any other related genus, such as Phasianus. Our analyses also suggest that northern China represents one region of the earliest chicken domestication, possibly dating as early as 10,000 y B.P. Similar to the evidence from pig domestication, our results suggest that these early domesticated chickens contributed to the gene pool of modern chicken populations. Moreover, our results support the idea that multiple members of the genus Gallus, specifically Gallus gallus and Gallus sonneratii contributed to the gene pool of the modern domestic chicken. Our results provide further support for the growing evidence of an early mixed agricultural complex in northern China.

Genotypic diversity of an invasive plant species promotes litter decomposition and associated processes.

Following studies that showed negative effects of species loss on ecosystem functioning, newer studies have started to investigate if similar consequences could result from reductions of genetic diversity within species. We tested the influence of genotypic richness and dissimilarity (plots containing one, three, six or 12 genotypes) in stands of the invasive plant Solidago canadensis in China on the decomposition of its leaf litter and associated soil animals over five monthly time intervals. We found that the logarithm of genotypic richness was positively linearly related to mass loss of C, N and P from the litter and to richness and abundance of soil animals on the litter samples. The mixing proportion of litter from two sites, but not genotypic dissimilarity of mixtures, had additional effects on measured variables. The litter diversity effects on soil animals were particularly strong under the most stressful conditions of hot weather in July: at this time richness and abundance of soil animals were higher in 12-genotype litter mixtures than even in the highest corresponding one-genotype litter. The litter diversity effects on decomposition were in part mediated by soil animals: the abundance of Acarina, when used as covariate in the analysis, fully explained the litter diversity effects on mass loss of N and P. Overall, our study shows that high genotypic richness of S. canadensis leaf litter positively affects richness and abundance of soil animals, which in turn accelerate litter decomposition and P release from litter.

[Study on fingerprint of shengxuening tablets].

To establish a method for studying fingerprint of Shengxuening tablets. With chlorin e6 as the reference substance, SHISEIDO Capcell-pak C18 (4.6 mm x 250 mm, 5 microm) analytical column was adopted and eluted with 0.2% formic acid ( containing 20 mmol x L(-1) TBAB) (A) and acetonitrile-methanol-acetone (50: 50: 5) (B). The detection wavelength was set 392 nm. The volume flow rate was 1.0 mL x min(-1). The temperature of column was 45 degrees C. Totally 10 common peaks were indicated on the HPLC fingerprint, with RSDs for variable retention values in common peaks below 0.50%. UPLC/DAD/Q-TOF-MS xevo G2 Q-TOF LC/MS was adopted to preliminarily indentify six chromatographic peaks. The main ingredient in Shengxuening tablets was ferrous derivative, which was mainly composed of Fe chlorin p6, Fe chlorin e6 and Fe isochlorin e4.

Habitat loss other than fragmentation per se decreased nuclear and chloroplast genetic diversity in a monoecious tree.

Generally, effect of fragmentation per se on biodiversity has not been separated from the effect of habitat loss. In this paper, using nDNA and cpDNA SSRs, we studied genetic diversity of Castanopsis sclerophylla (Lindl. & Paxton) Schotty populations and decoupled the effects of habitat loss and fragmentation per se. We selected seven nuclear and six cpDNA microsatellite loci and genotyped 460 individuals from mainland and island populations, which were located in the impoundment created in 1959. Number of alleles per locus of populations in larger habitats was significantly higher than that in smaller habitats. There was a significant relationship between the number of alleles per locus and habitat size. Based on this relationship, the predicted genetic diversity of an imaginary population of size equaling the total area of the islands was lower than that of the global population on the islands. Re-sampling demonstrated that low genetic diversity of populations in small habitats was caused by unevenness in sample size. Fisher's α index was similar among habitat types. These results indicate that the decreased nuclear and chloroplast genetic diversity of populations in smaller habitats was mainly caused by habitat loss. For nuclear and chloroplast microsatellite loci, values of F(ST) were 0.066 and 0.893, respectively, and the calculated pollen/seed dispersal ratio was 162.2. When separated into pre-and post-fragmentation cohorts, pollen/seed ratios were 121.2 and 189.5, respectively. Our results suggest that habitat loss explains the early decrease in genetic diversity, while fragmentation per se may play a major role in inbreeding and differentiation among fragmented populations and later loss of genetic diversity.

[Effect of Bufei Qingyu Granule in mollifying skin of mouse scleroderma model].

OBJECTIVE: To investigate the effect and mechanism of Bufei Qingyu Granule (BQG) in mollifying the skin of scleroderma model mice. METHODS: Scleroderma model induced with bleomycin in BALB/C mice 8-weeks old were administered with different dose of BQG for 26 days. The pathological changes of the mice skin were observed. RESULTS: Treatment with low, medium and high dose of BQG showed a tendency to ameliorate the thickened dermis in scleroderma mice but without statistical significance. Medium and high dose of BQG reduced the perivasculitis of dermis and alleviated the reduction or deletion of accessory structure, such as hair follicle and sweat gland. And the spleen index was lower markedly in mice treated with BQG of any dose than that in the untreated model mice (P < 0.05). CONCLUSION: BQG could ameliorate the sclerosed skin in model mice and prevent the occurrence of splenomegaly.