Univariable and multivariable mendelian randomization study revealed the modifiable risk factors of urolithiasis.

BACKGROUND: Urolithiasis is a common urological disease with increasing incidence worldwide, and preventing its risk poses significant challenges. Here, we used Mendelian randomization (MR) framework to genetically assess the causal nature of multifaceted risk factors on urolithiasis. METHODS: 17 potential risk factors associated with urolithiasis were collected from recently published observational studies, which can be categorized basically into lifestyle factors and circulating biomarkers. The instrumental variables of risk factors were selected from large-scale genome-wide association studies (N ≤ 607,291). Summary-level data on urolithiasis were obtained from UK Biobank (UKB) (3,625 cases and 459,308 noncases) and the FinnGen consortium (5,347 cases and 213,445 noncases). The univariable and multivariable MR analyses were applied to evaluate the causal, independent effect of these potential risk factors upon urolithiasis. Effects from the two consortia were combined by the meta-analysis methods. RESULTS: Higher genetically predicted sex hormone-binding globulin (SHBG, OR, 0.708; 95% CI, 0.555 to 0.903), estradiol (OR, 0.179; 95% CI, 0.042 to 0.751), tea intake (OR, 0.550; 95% CI, 0.345 to 0.878), alcoholic drinks per week (OR, 0.992; 95% CI, 0.987 to 0.997), and some physical activity (e.g., swimming, cycling, keeping fit, and bowling, OR, 0.054; 95% CI, 0.008 to 0.363) were significantly associated with a lower risk of urolithiasis. In the Multivariate Mendelian Randomization (MVMR) analyses, the significant causal associations between estradiol, SHBG, tea intake, and alcoholic drinks per week with urolithiasis were robust even after adjusting for potential confounding variables. However, the previously observed causal association between other exercises and urolithiasis was no longer significant after adjusting for these factors. CONCLUSIONS: The univariable and multivariable MR findings highlight the independent and significant roles of estradiol, SHBG, tea intake, and alcoholic drinks per week in the development of urolithiasis, which might provide a deeper insight into urolithiasis risk factors and supply potential preventative strategies.

Phase-change material cooling blanket: A feasible cooling choice during transport after exercise-induced hyperthermia.

BACKGROUND: Exercise-induced hyperthermia preceding the onset of exertional heatstroke requires a rapid reduction in the body core temperature (Tcore) to ensure safety. In recent years, phase-change material (PCM) cooling devices have been increasingly used for rapid cooling after hyperthermia due to their superior capacity for heat absorption. OBJECTIVES: This study aimed to evaluate the cooling performance and effectiveness of a PCM cooling blanket on heart rate (HR) and heart rate variability (HRV) recovery after exercise-induced hyperthermia. DESIGN: Randomized cross-over. METHODS: The study participants were 12 male volunteers who were engaged in professional training and completed an endurance exercise for approximately 30 min in a hot and humid environment (temperature ≈ 30 °C; relative humidity ≈ 66%). The participants underwent a 30-min cooling trial after exercise, receiving either treatment with a PCM cooling blanket (PCM group) or natural cooling (CON group). The Tcore, HR, and HRV time-domain indices were used for analysis. RESULTS: The Tcore values were significantly lower in the PCM group during cooling. Reductions in the Tcore from precooling to 20 min of cooling were significantly greater in the PCM group than in the CON group. The HR in the PCM group was lower than that recorded in the CON group at 10 and 20 min of cooling. The reduction in HR during cooling from precooling was also significantly greater in the PCM group. HRV time-domain indices during cooling in the PCM group were significantly lower compared with the CON group while elevations in some HRV time-domain indices from precooling to postcooling were significantly greater in the PCM group than in the CON group. CONCLUSIONS: The PCM cooling blanket had good cooling performance and the ability to hasten recovery of both HR and HRV. It may serve as a feasible cooling choice during transport after exercise-induced hyperthermia.

Physicochemical Properties of Granular and Gelatinized Lotus Rhizome Starch with Varied Proximate Compositions and Structural Characteristics.

As a traditional and popular dietary supplement, lotus rhizome starch (LRS) has health benefits for its many nutritional components and is especially suitable for teenagers and seniors. In this paper, the approximate composition, apparent amylose content (AAC), and structural characteristics of five LRS samples from different regions were investigated, and their correlations with the physicochemical properties of granular and gelatinized LRS were revealed. LRS exhibited rod-shaped and ellipsoidal starch granules, with AAC ranging from 26.6% to 31.7%. LRS-3, from Fuzhou, Jiangxi Province, exhibited a deeper hydrogel color and contained more ash, with 302.6 mg/kg iron, and it could reach the pasting temperature of 62.6 °C. In comparison, LRS-5, from Baoshan, Yunnan Province, exhibited smoother granule surface, less fragmentation, and higher AAC, resulting in better swelling power and freeze-thaw stability. The resistant starch contents of LRS-3 and LRS-5 were the lowest (15.3%) and highest (69.7%), respectively. The enzymatic digestion performance of LRS was positively correlated with ash content and short- and long-term ordered structures but negatively correlated with AAC. Furthermore, the color and network firmness of gelatinized LRS was negatively correlated with its ash content, and the retrograde trend and freeze-thaw stability were more closely correlated with AAC and structural characteristics. These results revealed the physicochemical properties of LRS from different regions and suggested their advantages in appropriate applications as a hydrogel matrix.

[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

Phytochemical Profile and Anti-Inflammatory Activity of the Fraction from Artemisia lavandulaefolia.

Artemisia lavandulaefolia, a traditional herbal medicine, has been utilized as anti-inflammatory and analgesia agent in clinic. Bioassay-guided fractionation resulted in a fraction (ALDF) with anti-inflammatory effect obtained from A. lavandulaefolia. Its main constituents were analyzed and identified by UPLC-ESI-Q-TOF-MS technology. ALDF showed the strong inhibitory activity on the nitrogen oxide (NO) production in LPS-induced RAW 264.7 macrophages with an IC50 value of 1.64±0.41 µg/mL. Further results displayed that ALDF also significantly suppressed the secretion of key pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2 ) and interleukin-1ß (IL-1ß), and the increase of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression induced by LPS stimulation. Mechanism study indicated that ALDF was able to block NF-κB signaling pathway through inhibiting IκB and p65 phosphorylation, as well as NF-κB p65 nuclear translocation. Furthermore, in vivo results in mice revealed that treatments with ALDF evoked significant inhibition on ear edema induced by xylene and on the writhing responses induced by acetic acid. These results suggest that ALDF holds great potential in the prevention and treatment of inflammatory disorders.

Effect of Auricularia auricula fermentation broth on the liver and stomach of mice with acute alcoholism.

In this paper, the protective effect of Auricularia auricula (A. auricula) fermentation broth on the liver and stomach of mice with acute alcoholism was studied. The A. auricula fermentation broth was prepared by adding Bacillus subtilis, lactic acid bacteria, and Saccharomyces cerevisiae to A. auricula solution. The changes of physical and chemical indexes during the fermentation of A. auricula were monitored, and the results showed the content of polysaccharides and protein in the two kinds of fermentation broth after the fermentation was completed. Furthermore, the characteristic structures of active substances such as proteins, polysaccharides and phenolics were found in the A. auricula fermentation by structural analysis. Antioxidant activity test results showed that the A. auricula fermentation broth had a strong ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. Cell experiments showed that the fermentation broth of A. auricula could significantly enhance the activity of NRK cells and protect NRK cells from H2O2 damage. Animal experiments showed that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and significantly reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG) in serum. These results indicated that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and could be used as a potential functional food to prevent liver and stomach damage caused by acute alcoholism.

Nitric Oxide Production Inhibitory Eudesmane-Type Sesquiterpenoids from Artemisia argyi.

Six new eudesmane-type sesquiterpene derivatives, artemargyinins A-F were isolated from the leaves of Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. Artemargyinins A-F feature a lactone ring-opening eudesmane-type sesquiterpene with an isoprenoid group at C(8). All compounds were tested for their inhibitory effects on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 macrophages. Artemargyinins A-F showed more potent NO production inhibitory activity with IC50 values ranging from 7.66±0.53 to 61.19±2.54 µM than the positive control quercetin (IC50 =74.34±1.39 µM). Among them, artemargyinins C and D exhibited strong inhibitory activity with IC50 values of 8.08±0.21 and 7.66±0.53 µM, respectively.

Triterpenoids with α-glucosidase inhibitory activity from Artemisia argyi.

Two new nordammarane-type triterpenoids, 3ß-acetoxy-20-oxo-21-nordammaran-23-carboxylic acid methyl ester (1) and 3ß-acetoxy-17ß-dammaranic acid (2), along with two known cycloartane-type triterpenoids (3-4), were isolated from the petroleum ether-soluble extract of Artemisia argyi. Their structures were elucidated based on 1D and 2D NMR spectroscopic data analysis. All compounds were evaluated for their α-glucosidase inhibitory activity in vitro. Compounds 1-4 exhibited significant inhibitory effects on α-glucosidase with IC50 values ranging from 38.34 ± 0.23 to 105.54 ± 0.33 µM.

Electrical Stimulation Degenerated Cochlear Synapses Through Oxidative Stress in Neonatal Cochlear Explants.

Neurostimulation devices use electrical stimulation (ES) to substitute, supplement or modulate neural function. However, the impact of ES on their modulating structures is largely unknown. For example, recipients of cochlear implants using electroacoustic stimulation experienced delayed loss of residual hearing over time after ES, even though ES had no impact on the morphology of hair cells. In this study, using a novel model of cochlear explant culture with charge-balanced biphasic ES, we found that ES did not change the quantity and morphology of hair cells but decreased the number of inner hair cell (IHC) synapses and the density of spiral ganglion neuron (SGN) peripheral fibers. Inhibiting calcium influx with voltage-dependent calcium channel (VDCC) blockers attenuated the loss of SGN peripheral fibers and IHC synapses induced by ES. ES increased ROS/RNS in cochlear explants, but the inhibition of calcium influx abolished this effect. Glutathione peroxidase 1 (GPx1) and GPx2 in cochlear explants decreased under ES and ebselen abolished this effect and attenuated the loss of SGN peripheral fibers. This finding demonstrated that ES induced the degeneration of SGN peripheral fibers and IHC synapses in a current intensity- and duration-dependent manner in vitro. Calcium influx resulting in oxidative stress played an important role in this process. Additionally, ebselen might be a potential protector of ES-induced cochlear synaptic degeneration.

Sesquiterpenoids from Artemisia argyi and their COXs inhibitory activities.

Four new sesquiterpene lactones, named artemargyinolides A-D (1-4), and seven known sesquiterpenoids (5-11) were isolated from Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. The absolute configuration of 1 was assigned by X-ray crystallographic analysis. Compound 1 is an unprecedented sesquiterpene dimer-monoterpene lactone. The cyclooxygenases (COX-1 and COX-2) inhibitory activities of all isolated compounds were evaluated. Compounds 1, 2, 4, and 6-11 showed inhibitory activity against COX-2 with IC50 values ranging from 35.78 ±â€¯0.39 to 256.07 ±â€¯0.38 µM. However, compounds 7, 9, and 10 exhibited weak inhibitory activity against COX-1 with IC50 values of 465.70 ±â€¯1.53, 281.43 ±â€¯3.56, and 490.45 ±â€¯6.07 µM, respectively. Other compounds are inactive against COX-1. Therefore, compounds 1, 2, 4, 6, 8, and 11 displayed selective COX-2 inhibitory activity.

Food-borne nanocarriers from roast beef patties for iron delivery.

Food-borne nanoparticles (FNs) produced during thermal processing of food may have potential as nanocarriers for Fe(ii) supplements. In this paper, the FNs in beef patties roasted for different times (15, 30, and 45 minutes) and the binding between FNs and ferrous ions were studied. The size of FNs decreased from 7.5 to 3.0 nm with the increase of baking time, and the FNs emitted bright blue fluorescence under ultraviolet light irradiation. The combination of FNs with ferrous ions was by means of the amino, hydroxyl and carboxyl functional groups on the particles. Cell viability study showed that the Fe(ii)-FNs increased the apoptotic rate, but significantly decreased the necrosis rate, which led to an increase in the number of living cells. In addition, the Fe(ii)-FNs can easily enter the Caco-2 cytoplasm, but not the cellular nucleus. The FNs derived from beef patties with an ultra-small size, high water solubility and plenty of functional groups might be good candidates as nanocarriers for Fe(ii) delivery.

[Research progress on anti-inflammatory mechanism of natural sesquiterpenoids].

Sesquiterpenoid is a kind of compound widely distributed in nature, which has a wide range of biological activities, such as anti-inflammatory, anti-tumor and immunomodulatory activities. This paper would review the anti-inflammatory mechanism of sesquiterpenoid. The mechanism is mainly by inhibiting the activation of nuclear factor (NF-κB), mitogen-activated protein kinase (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways and down-regulating the inflammatory gene expression including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-1(IL-1), IL-6, IL-8 and other inflammatory factors. Thereby, the production and release of inflammatory cytokines are reduced to exert anti-inflammatory effect. This review is intended to provide reference for related research.

Phthalide dimers from Angelica sinensis and their COX-2 inhibition activity.

Four new dimeric phthalides, angesinenolides C-F (1-4), along with three known ones, were isolated from the roots of Angelica sinensis. Their structures were determined by means of HRMS and NMR experiments. The structures of compounds 1 and 3 were confirmed using X-ray crystallographic data. All isolated compounds were tested for activities on the inhibition of COX-2 enzyme in vitro. Compounds 1-6 exhibited inhibitory activity against COX-2 with IC50 values ranging from 29.32 ±â€¯0.07 to 137.91 ±â€¯0.24 µM.

Sesquiterpene Lactones with COX-2 Inhibition Activity from Artemisia lavandulaefolia.

Two new sesquiterpene lactones, artelavanolides A (1) and B (2), and four known sesquiterpene lactones (3 - 6) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D-NMR and HR-ESI-MS). The absolute configuration of 1 was determined by the analysis of single-crystal X-ray diffraction data. Artelavanolide A (1) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)-C(1) that is probably formed through a rearrangement of the guaiane-type sesquiterpenoids. Artelavanolide B (2) is a new highly unsaturated guaianolide. Compounds 1 - 6 were tested for activities on the inhibition of COX-2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX-2 with IC50 values ranging from 43.29 to 287.07 µm compared with the positive control, celecoxib (IC50 = 18.10 µm). Among them, 3 showed the best COX-2 inhibitory activity with an IC50 value of 43.29 µm.

Two new flavonoids from Artemisia argyi with their anticoagulation activities.

A new flavone glycoside, eupatilin 7-O-ß-d-glucopyranoside (1) and a new flavone, 5,6,2',4'-tetrahydroxy-7,5'-dimethoxyflavone (2), were isolated from Artemisia argyi. Their structures were unambiguously elucidated by extensive spectroscopic analysis. Both flavonoids were evaluated for in vitro anticoagulation activities. Compound 1 significantly extended thrombin time. Compound 2 had obvious effect in increasing prothrombin time.

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016.

Phthalide Derivatives with Anticoagulation Activities from Angelica sinensis.

Two new phthalide derivatives, angesinenolides A and B (1 and 2), were isolated from the roots of Angelica sinensis. Their structures were elucidated using HRMS, NMR, and X-ray crystallographic data. Compound 1 is the first example of a phthalide trimer presumably formed through two [2+2] cycloaddition reactions. Compound 2 is a unique dimeric phthalide with a peroxy bridge between C-3a and C-6. Both phthalides were evaluated for in vitro anticoagulation activities. Compound 1 reduced the level of fibrinogen (FIB). Compound 2 significantly extended thrombin time and activated partial thromboplastin time, as well as markedly reduced the content of FIB.

Geranyl flavonoids from Robinia pseudoacacia.

A new geranyl flavonol, robipseudin A (1), and a known geranyl flavone, kuwanon S (2), were isolated from the leaves of Robinia pseudoacacia. The structure of the new compound was determined by spectroscopic methods. Compounds 1 and 2 showed moderate antioxidant activities in the DPPH radical scavenging assay.

Japonicasins A and B, two new isoprenylated flavanones from Sophora japonica.

Two new flavanones with a C15 isoprenoid group, japonicasins A and B (1 and 2), were isolated from the leaves of Sophora japonica. This is the first report on the presence of the (2E,7E)-6-isopropyl-3,9-dimethyldeca-2,7,9-trien-1-yl group (C15 isoprenoid group) in isoprenylated flavonoids. Their structures were determined by spectroscopic methods, including UV, IR, 1D and 2D NMR, HRESIMS, and CD experiments. In addition, the antioxidant activities of compounds 1 and 2 were determined through DPPH radical scavenging assays. They exhibited potential antioxidant activities, with IC50 values of 35.1±0.8 µM and 88.7±1.1 µM for compounds 1 and 2, respectively.

Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys.

BACKGROUND: Caspase 3 associated with apoptosis and inflammation plays a key role in ischemia-reperfusion injury. The efficacy of naked caspase 3 small interfering RNA (siRNA) has been proved in an isolated porcine kidney perfusion model but not in autotransplantation. MATERIALS AND METHODS: The left kidney was retrieved from mini pigs and infused with the University of Wisconsin solution with or without 0.3mg of caspase 3 siRNA into the renal artery with the renal artery and vein clamped for 24-h cold storage (CS). After right nephrectomy, the left kidney was autotransplanted into the right for 48 h without systemic treatment of siRNA. RESULTS: Fluorescent dye-labeled caspase 3 siRNA was visualized in the post-CS kidneys but was weakened after transplantation. The expression of caspase 3 messenger RNA and precursor was downregulated by siRNA in the post-CS kidneys. In the siRNA-preserved posttransplant kidneys, however, the caspase 3 messenger RNA and active subunit were upregulated with further decreased precursor but increased active caspase 3+ cells, apoptotic cells, and myeloperoxidase+ cells. Moreover, the renal tissue damage was aggravated by siRNA, whereas the renal function was not significantly changed. CONCLUSIONS: Naked caspase 3 siRNA administered into the kidney was effective in cold preservation but not enough to protect posttransplant kidneys, which might be because of systemic complementary responses overcoming local effects.