Ellagic acid-enhanced biocompatibility and bioactivity in multilayer core-shell gold nanoparticles for ameliorating myocardial infarction injury.

BACKGROUND: Myocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations. RESULTS: We have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins. CONCLUSIONS: These findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications.

Structural characterization and mechanisms of macrophage immunomodulatory activity of a novel polysaccharide with a galactose backbone from the processed Polygonati Rhizoma.

A purified polysaccharide with a galactose backbone (SPR-1, Mw 3,622 Da) was isolated from processed Polygonati Rhizoma with black beans (PRWB) and characterized its chemical properties. The backbone of SPR-1 consisted of [(4)-ß-D-Galp-(1]9 â†’ 4,6)-ß-D-Galp-(1 â†’ 4)-α-D-GalpA-(1 â†’ 4)-α-D-GalpA-(1 â†’ 4)-α-D-Glcp-(1 â†’ 4,6)-α-D-Glcp-(1 â†’ 4)-α/ß-D-Glcp, with a branch chain of R1: ß-D-Galp-(1 â†’ 3)-ß-D-Galp-(1→ connected to the →4,6)-ß-D-Galp-(1→ via O-6, and a branch chain of R2: α-D-Glcp-(1 â†’ 6)-α-D-Glcp-(1→ connected to the →4,6)-α-D-Glcp-(1→ via O-6. Immunomodulatory assays showed that the SPR-1 significantly activated macrophages, and increased secretion of NO and cytokines (i.e., IL-1ß and TNF-α), as well as promoted the phagocytic activities of cells. Furthermore, isothermal titration calorimetry (ITC) analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant (K D) of 18.8 µM. It was suggested that SPR-1 activated the immune response through Toll-like receptor 4 (TLR4) signaling and downstream responses. Our research demonstrated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response, and also provided an easily accessible way that can be used for PR deep processing.

Impact of extraction method on the lipids of Himalayan marmot oil with ultrahigh-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry analysis.

RATIONALE: Himalayan marmot oil (SPO) has been used for pharmaceutical purposes for centuries, but its composition is still unclear. The bioactivity of SPO highly depends on the techniques used for its processing. This study focused on the comprehensive lipidomics of SPO, especially on the ones derived from dry rendering, wet rendering, cold pressing, and ultrasound-assisted solvent extraction. METHODS: We performed lipid profiling of SPO acquired by different extraction methods using ultrahigh-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry, and 17 classes of lipids (2 BMPs, 12 LysoPCs, 9 LysoPEs, 41 PCs, 24 PEs, 23 Plasmenyl-PCs, 10 Plasmenyl-PEs, 10 MGs, 63 DGs, 187 TGs, 2 MGDGs, 3 Cer[NDS]s, 22 Cer[NS]s, 2 GlcCer[NS]s, 14 SMs, 14 CEs, and 6 AcylCarnitines) were characterized. RESULTS: Fifty-five lipids were differentially altered (VIP > 1.5, p < 0.05) between the extraction techniques, which can be used as potential biomarkers to differentiate SPO extracted by various methods. Additionally, the contents of oleic acid and arachidic acid were abundant in all samples that may suggest their medicinal values and are conducive to in-depth research. CONCLUSIONS: These findings reveal the alterations of lipid profile and free fatty acid composition in SPO obtained with different extraction methods, providing a theoretical foundation for investigating its important components as functional factors in medicines and cosmetics.

Preclinical Investigations on Anti-fibrotic Potential of Long-Term Oral Therapy of Sodium Astragalosidate in Animal Models of Cardiac and Renal Fibrosis.

In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1ß, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-ß1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis.

Surface hydrolysis-designed AuNPs-zwitterionic-glucose as a novel tool for targeting macrophage visualization and delivery into infarcted hearts.

Macrophages, innate immune cells, are key players in the maintenance of myocardial homeostasis under normal conditions and tissue repair after injury. The infiltration of macrophages into the injured heart makes them a potentially appealing vehicle for noninvasive imaging and targeted drug delivery of myocardial infarction (MI). In this study, we demonstrated the use of surface hydrolysis-designed AuNPs-zwitterionic-glucose to label macrophages and track their infiltration into isoproterenol hydrochloride (ISO)-induced MI sites noninvasively using CT. The AuNPs-zwitterionic-glucose did not affect the viability or cytokine release of macrophages and were highly taken up by these cells. The in vivo CT images were obtained on Day 4, Day 6, Day 7, and Day 9, and the attenuation was seen to increase in the heart over time compared to the Day 4 scan. In vitro analysis also confirmed the presence of macrophages around injured cardiomyocytes. Additionally, we also addressed the concern of cell tracking or merely AuNP tracking, which is the inherent problem for any form of nanoparticle-labeled cell tracking by using zwitterionic and glucose-functionalized AuNPs. The glucose coated on the surface of AuNPs-zwit-glucose will be hydrolyzed in macrophages, forming only zwitterionic protected AuNPs that cannot be taken up again by endogenous cells in vivo. This will greatly improve the accuracy and precision of imaging and target delivery. We believe this is the first study to noninvasively visualize the infiltration of macrophages into MI hearts using CT, which could be used for imaging and evaluating the possibility of macrophage-mediated delivery in infarcted hearts.

Fast and Specific Screening of EPA/DHA-Enriched Phospholipids in Fish Oil Extracted from Different Species by HILIC-MS.

Eicosapentaenoic acid- and docosahexaenoic acid-enriched phospholipids (PLEPA/DHA) have versatile health-beneficial functions and can be well absorbed in the intestine. Herein, a precursor ion scan-driven hydrophilic interaction chromatography mass spectrometry (PreIS-HILIC-MS) method with the fatty acyl moieties of m/z 301.6 and 327.6 locked was established to specifically and selectively screen PLEPA/DHA in different fish oil samples, including saury, grass carp, hairtail, and yellow croaker. Taking saury oil as an example, a total of 24 PLEPA/DHA were successfully identified and quantified, including 20 PCEPA/DHA and 4 PEEPA/DHA. Finally, this method was validated in terms of sensitivity (limit of detection ≤ 4.15 µg·mL-1), linearity (≥0.9979), precision (RSDintraday ≤ 4.65%), and recovery (≥78.6%). The performance of the PreIS-HILIC-MS method was also compared with that of the traditional full-scan mode, and the former demonstrated its unique superiority in targeted screening of PLEPA/DHA in fish oils.

Phospholipidomics quality evaluation of swimming crabs (Portunus trituberculatus) cultured with formulated feed, frozen trash fish, and mixed feed, a non-target approach by HILIC-MS.

Swimming crab, Portunus trituberculatus, is popularly consumed because of its flavor and nutritional value. Herein, the crabs cultivated with formulated feed, frozen trash fish, and mixed feed were lipidomically analyzed by non-target HILIC-QTRAP/MS. The results showed that there were four phospholipid classes comprising 81 molecular species with plenty of polyunsaturated fatty acyl chains observed. The formulated feed group owned the highest content of phospholipids (332.91 µg·mg-1), followed by the frozen trash fish group (294.74 µg·mg-1) and mixed feed group (279.74 µg·mg-1). The effect of feeding modes was compared statistically, and the most contributing variables of m/z 802 (PC 34:2), m/z 846 (ether PC o-38:1), m/z 792 (PE 40:5), etc. were screened out and verified. The phospholipidomics results indicated that the formulated feed could replace frozen trash fish for the cultivation of P. trituberculatus.

Untargeted Screening of EPA/DHA Structured Phospholipids in Krill Oil by Chain-Lock-Driven Hydrophilic Interaction Liquid Chromatography Tandem Mass Spectrometry.

Eicosapentaenoic and docosahexaenoic acids structured phospholipids (PLEPA/DHA) have multiple biochemical and pharmacological effects on human health. In this study, EPA and DHA chains were locked under precursor ion scan (PreIS) mode for untargeted screening PLEPA/DHA in krill oil using hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS). The effect of collision energy and declustering potential on the fragmentation of EPA (m/z 301.2) and DHA (m/z 327.2) chains was studied. A total of 33 PLEPA/DHA were characterized (sn-1/sn-2) and quantified using regression models, including 16 PCEPA/DHA, 11 PEEPA/DHA, and 6 PIEPA/DHA. Afterward, this method was validated in terms of linearity (≥0.9978), sensitivity (LOD ≤ 4.02 µg·L-1), precision (RSDintraday ≤ 4.71%), and recovery (≥78.9%). Finally, the performance of HILIC-PreIS-MS/MS was compared with those of conventional methods, and the results indicated its superiority in selective screening PLEPA/DHA in krill oil.

In situ and real-time authentication of Thunnus species by iKnife rapid evaporative ionization mass spectrometry based lipidomics without sample pretreatment.

Tuna adulteration and mislabeling are serious problem worldwide and have caused economic loss and consumer rights violation. In this study, an electrometric knife (iKnife) coupling rapid evaporative ionization mass spectrometry (REIMS) and a multivariate recognition model were developed and employed for in situ and real-time authentication of four tuna species without sample preparation. The results showed that the lipidomic profiles were successfully acquired and the differences in fatty acids and phospholipids were statistically analyzed to be significant (p < 0.05). The model displayed the superb classification accuracy (>93%) and validation (R2(Y) = 0.992, Q2 = 0.986), and the main contributors of m/z 817.64, m/z 809.68, etc. were screened out to be used as potential biomarkers. Based on this technique, the identity of blind tuna samples could be unambiguously authenticated with the results displayed on a monitor screen directly. This study provided a front-line rapid detection method to prove the authenticity of tuna species.

Real-Time Monitoring of the Oxidation Characteristics of Antarctic Krill Oil (Euphausia superba) during Storage by Electric Soldering Iron Ionization Mass Spectrometry-Based Lipidomics.

Antarctic krill oil (AKO) is susceptible to oxidation due to the high unsaturation degree of bioactive substances. Herein, a lipidomics method for in situ monitoring of the dynamic oxidation characteristics in AKO was explored based on electric soldering iron ion source (ESII) coupling with rapid evaporative ionization mass spectrometry (REIMS). The lipidomics profiles of AKO at different storage periods were successfully acquired. On the basis of principal component analysis and orthogonal partial least-squares analysis, the obtained REIMS data were employed to build a multivariate recognition model. The ions of m/z 707.50, 721.50, 833.49, and 837.54 contributed the most significant effect on the multivariate data model for the authentication of different AKO samples. Besides, the variation of viscosity, astaxanthin, and volatile compounds were also evaluated to corroborate the oxidation characteristics. The results indicated that the ESII-REIMS technology could be applied as an advanced rapid detection method to secure oil and fat quality during storage.

Electric Soldering Iron Ionization Mass Spectrometry Based Lipidomics for in Situ Monitoring Fish Oil Oxidation Characteristics during Storage.

An electric soldering iron ion source (ESII) coupling with rapid evaporative ionization mass spectrometry (REIMS) was developed and used for in situ monitoring the dynamic variation trend in oxidation characteristics of fish oil during storage. The lipidomics profiles of fish oil stored at various days were acquired by ESII-REIMS. The fatty acid and triacylglycerol species were structurally identified, and their abundances were analyzed according to multivariate statistical models mainly including principle component analysis as well as orthogonal partial least-squares analysis. On the shared and unique structure plot, the ions of m/z 255.23, 281.24, 877.72, and 901.72 displayed the most significant variation among the oxidized fish oil samples. Based on receiver operating characteristic curve analysis with an optimal Youden index of 0.91, these markers were further verified. The variation of viscosity and volatiles were also evaluated to further verify the oxidation characteristics of fish oil. The study demonstrated that ESII-REIMS technology used as an advanced detection method could ensure fish oil quality during storage.

Lipidomics differentiation of soft-shelled turtle strains using hydrophilic interaction liquid chromatography and mass spectrometry.

Hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS) was used as an accurate and sensitivity technique to separate and characterize the phospholipids in three strains of soft-shelled turtles. Under the optimized experimental parameters, the lipidomic profiles were successfully acquired, and a total of 55 phospholipid molecular species were identified. The principal component analysis (PCA) was applied to normalize the relative amounts of the phospholipid molecular species and revealed the differences among three strains of soft-shelled turtle, including Qingxi Huabie (QXH, GS-01-003-2008), Zhexin Wubie (ZXW, GS-02-005-2015), and Zhewu Erhao (ZWE, unregistered). Comparing with other methods, HILIC-MS is rapid, efficient and suitable in determining and visualizing phospholipids. This method also can be used for authenticating different strains of soft-shelled turtles.

Rapid Evaporative Ionization Mass Spectrometry-Based Lipidomics Tracking of Grass Carp ( Ctenopharyngodon idellus) during In Vitro Multiple-Stage Digestion.

A rapid evaporative ionization mass spectrometry (REIMS) method was developed for lipidomics tracking of Ctenopharyngodon idellus during in vitro multiple-stage digestion. The REIMS conditions were optimized such that the temperature of the heating probe was 500 °C, sample amount was 30 mg, and the flow rate of auxiliary solvent was 100 µL min-1. The results showed that the phospholipids were detected with variety and quantity in the crude and multiple-stage digested samples. The enzymatic effect on the phospholipids is varied depending on the phospholipid classes, and the hydrolysis rate of phospholipids increased as the degree of unsaturation of the acyl chain increased. The principal component analysis (PCA) indicated that the ions at m/ z 809.61, 811.63, and 857.52 were the most noticeable species digested during the process. This method exhibited great potential in fast lipidomics profiling for inspecting the characteristics of nutritional lipid absorption digestion in human gastrointestin.

Relationship between anogenital distance and cryptorchidism in human newborns / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the relation of the anogenital distance (AGD) with cryptorchidism in male newborns.</p><p><b>METHODS</b>This study included 350 male infants delivered in two community hospitals between September 2013 and September 2014. Within 24 hours after birth, a pediatric surgeon measured the AGD of the neonates and determined whether they had cryptorchidism. According to the testicular position, we divided the undescended testes into three types: upper scrotal, inguinal, and non-palpable.</p><p><b>RESULTS</b>Totally 39 cases of cryptorchidism were found in the 350 newborns. The AGD of the cryptorchidism infants was significantly shorter than that of the normal neonates ([2.01 ± 0.22] vs [2.35 ± 0.19] cm, P < 0.01), and statistically significant differences remained even when preterm and low birth-weight infants were excluded ([2.32 ± 0.14] vs [2.06 ± 0.19] cm; (2.37 ± 0.17) cm vs (2.12 ± 0.12) cm, all P < 0.01). The newborns with higher-position cryptorchidism had a shorter AGD, though with no significant difference (F = 0.434, P > 0.05). No significant differences were observed in the AGD between unilateral and bilateral cryptorchidism ([1.96 ± 0.13] vs [2.02 ± 0.17] cm, P > 0.05).</p><p><b>CONCLUSION</b>Shorter AGD is associated with a higher incidence of cryptorchidism in male newborns. AGD could serve as a potential biomarker for disruption of androgen action during the male programming window period.</p>