A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Dihydroisocoumarins from the Mangrove-Derived Fungus Penicillium citrinum.

Three new dihydroisocoumarin penicimarins G-I (1-3), together with one known dihydroisocoumarin (4) and three known meroterpenoids (5-7), were obtained from a fungus Penicillium citrinum isolated from the mangrove Bruguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of spectroscopic data. The absolute configuration of 1 was determined by the X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of 2 and 3 were determined by comparison of their circular dichroism (CD) spectra with the literature. All compounds were evaluated for their antibacterial activities and cytotoxic activities.

Left bundle branch area pacing improving the left atrial outcomes in pace-dependent patients compared with right ventricular outflow tract septal pacing.

BACKGROUND: Recent studies suggested that the left bundle branch area pacing (LBBAP) has a better efficacy to reduce QRS duration and produce a lower pacing threshold than the conventional right ventricular outflow tract septal pacing (RVOP), which resulted in a better cardiac function and ventricular synchronization. However, whether the LBBAP has a better efficacy in improving left atrial structure, function in pace-dependent patients compared with RVOP has not been well studied. OBJECTIVE: The purpose of this study was to compare the atrial outcomes of pace-dependent patients who received LBBAP or RVOP procedures. METHODS AND RESULTS: A total of 72 patients (including II° AVB, high AVB, and III° AVB, excluding atrial fibrillation patients with atrioventricular block) consecutively enrolled in this single-center prospective clinical study and randomly assigned to the RVOP group and the LBBP group with 36 patients. All patients were pace-dependent. The changes in echocardiogram, speckle-tracking echocardiography, brain natriuretic peptide (BNP), and 6-min walking distance were documented and compared between two groups at baseline, 7 days, 1, 3, and 6 months after the implantation. There were no significant differences in baseline characteristics between the two groups. The results of the study were as following: (1) left atrial structure index: Our study indicated that there are no significant differences in left atrial anteroposterior dimension (LAAPD), left atrial superoinferior dimension, and left atrial mediolateral dimension between two groups. While the LAAPD in the LBBAP group was significantly reduced at 6 months after implantation ([38.22 ± 2.17] mm vs. [34.13 ± 1.59] mm, p < .05). (2) Left atrial strain index: We observed that the S% was significantly improved in both groups at 3 and 6 months after implantation but more prominent in the LBBAP group at 6 months (36.94 ± 11.67 vs. 25.87 ± 8.93, p = .01). SRs, SRe were improved in the RVOP group at 6 months after implantation but was further significantly increased in the LBBAP group. Similarly, the SRa in the LBBAP group was significantly better than the RVOP group after 6 months (-2.11 ± 0.75 vs. -2.51 ± 0.70, p = .04). (3) Left atrial ejection index: LAEF% in the LBBAP group was significantly improved compared with the RVOP group (60.02 ± 1.88 vs. 53.65 ± 2.45, p = .047) and baseline (60.02 ± 1.88 vs. 49.68 ± 2.75, p < .05) at 6 months after the surgery. (4) Left ventricular ejection index: The LVEF% in the LBBAP group was significantly increased than the RVOP group after 6 months (69.14 ± 4.99 vs. 64.60 ± 4.84, p = .01) and the BNP level was significantly lower in the LBBAP group compared with the RVOP group at 7 days, 1, 3, and 6 months after implantation (p < .05). (5) 6-min walking distance: the 6-min walking distance was significantly increased at 3 and 6 months after implantation compared with that before (p < .05) in both groups, but was more prominent in LBBAP groups ([483.03 ± 11.02] m vs. [431.09 ± 10.69] m,p < .05). CONCLUSION: Compared with the traditional RVOP, the LBBAP procedure increased left atrial myocardial stress as well as left atrial ejection in pace-dependent patients at follow-up to 6 months.

A pH-neutral bioactive glass empowered gelatin-chitosan-sodium phytate composite scaffold for skull defect repair.

The ideal skull defect repairing material should have good biocompatibility and mechanical properties, and contribute to osteogenesis. In this study, we designed and fabricated biodegradable, bioactive and mechanically robust porous scaffolds composed completely of biological materials. We used a gelatin-chitosan blend as the matrix, sodium phytate instead of toxic glutaraldehyde for cross-linking, and the pH-neutral bioactive glass (PSC) to improve biological activity and mechanical properties. The chitosan-gelatin-30%PSC/sodium phytate composite scaffold avoided the problems of high toxicity in conventional cross-linking agents with glutaraldehyde, the poor mechanical support of the pure chitosan or gelatin scaffold, and the mismatch of the degradation rate with bone repair, becoming a promising new candidate for skull defect repair.

Comparison of Adverse Events between Isolated Left Atrial Appendage Closure and Combined Catheter Ablation.

(1) Background: This study aimed to investigate the effect of an additional catheter ablation (CA) procedure on the risk of post-procedure adverse events during CA combined with left atrial appendage closure (LAAC). (2) Methods: From July 2017 to February 2022, data from 361 patients with atrial fibrillation who underwent LAAC at our center were analyzed retrospectively. The adverse events were compared between CA + LAAC and LAAC-only groups. (3) Results: The incidence of device-related thrombus (DRT) and embolic events was significantly lower in the CA + LAAC group than in the LAAC-only group (p = 0.01 and 0.04, respectively). A logistic regression analysis revealed that the combined procedure served as a protective factor for DRT (OR = 0.09; 95% confidence interval: 0.01-0.89; p = 0.04). Based on a Cox regression analysis, the risk of embolism marginally increased in patients aged ≥65 years (HR = 7.49, 95% CI: 0.85-66.22 p = 0.07), whereas the combined procedure was found to be a protective factor (HR = 0.25, 95% CI: 0.07-0.87 p = 0.03). Further subgroup and interaction analyses revealed similar results. (4) Conclusions: The combined procedure may be associated with a lower rate of post-procedure DRT and embolization without a higher occurrence of other adverse events after LAAC. A risk-score-based prediction model was conducted, showing a good prediction performance.

Fucoidan from sea cucumber Cucumaria frondosa exhibits anti-hyperglycemic effects in insulin resistant mice via activating the PI3K/PKB pathway and GLUT4.

The present study investigated the anti-hyperglycemic properties and mechanisms of fucoidan, isolated from Cucumaria frondosa (Cf-FUC), in insulin resistant mice. Male C57BL/6J mice were fed regular diet or high-fat/high-sucrose diet for 19 weeks. Model animals were dietary administrated either rosiglitazone (RSG, 1 mg/kg·bw), fucoidan (Cf-FUC, 80 mg/kg·bw) or their combinations. Results showed that Cf-FUC significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance and insulin tolerance in insulin-resistant mice. Quantitative real-time PCR analysis showed that Cf-FUC increased the mRNA expressions of insulin receptors (IR), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4). Western blot assays demonstrated that Cf-FUC showed no effect on total protein expression but nevertheless enhanced the phosphorylation of proteins listed above and increased translocation of GLUT4 to the cell membrane. Furthermore, Cf-FUC enhanced the effects of RSG. These results indicated that Cf-FUC exhibited significant anti-hyperglycemic effects via activating PI3K/PKB pathway and GLUT4 in skeletal muscle and adipose tissue.

Sialoglycoprotein Isolated from Eggs of Carassius auratus Ameliorates Osteoporosis: An Effect Associated with Regulation of the Wnt/ß-Catenin Pathway in Rodents.

In the current study, ovariectomized (OVX) rats and the senescence-accelerated mouse strain P6 (SAMP6) were employed to establish models of postmenopausal osteoporosis and senile osteoporosis, respectively. The effects of treatment with sialoglycoprotein isolated from the eggs of Carassius auratus (Ca-SGP) on these two types of osteoporosis were investigated in vivo. Results showed that Ca-SGP significantly increased bone mineral density, ameliorated trabecular bone microstructure, and improved bone biomechanical properties in both OVX rats and SAMP6. The osteogenesis related Wnt/ß-catenin pathway was targeted to study the underlying mechanism of Ca-SGP activity. In postmenopausal osteoporosis, Ca-SGP suppressed the activation of Wnt/ß-catenin signal via down-regulating the expression of key genes including LRP5, ß-catenin, and Runx2, suggesting that overactive osteogenesis was controlled by Ca-SGP. The bone formation was sharply weakened in senile osteoporosis, whereas Ca-SGP treatment promoted osteoblast activity by stimulating the Wnt/ß-catenin signal. In conclusion, Ca-SGP ameliorated these two types of osteoporosis by normalizing bone anabolism.

Enrichment, Distribution of Vanadium-Containing Protein in Vanadium-Enriched Sea Cucumber Apostichopus japonicus and the Ameliorative Effect on Insulin Resistance.

Sea cucumbers are a potential source of natural organic vanadium that may improve insulin resistance. In this work, vanadium was accumulated rapidly in blood, body wall, and intestine by sea cucumber Apostichopus japonicus. Furthermore, water-soluble vanadium-containing proteins, the main form of the organic vanadium, were tentatively accumulated and isolated by a bioaccumulation experiment. It was also designed to evaluate the beneficial effect of vanadium-containing proteins (VCPs) from sea cucumber rich in vanadium on the development of hyperglycemia and insulin resistance in C57BL/6J mice fed with a high-fat high-sucrose diet (HFSD). HFSD mice treated with VCPs significantly decreased fasting blood glucose, serum insulin, and HOMA-IR values as compared to HFSD mice, respectively. Serum adiponectin, resistin, TNF-α, and leptin levels in insulin-resistant mice were dramatically reduced by a VCP supplement. These results show an ameliorative effect on insulin resistance by treatment with VCPs. Such compound seems to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes.

Sialoglycoproteins prepared from the eggs of Carassius auratus prevent bone loss by inhibiting the NF-κB pathway in ovariectomized rats.

In this study, we investigated the improvement of osteoporosis by sialoglycoproteins isolated from the eggs of Carassius auratus (Ca-SGP) in ovariectomized rats. Ca-SGP was supplemented to ovariectomized Sprague-Dawley rats for 90 days. The results showed that Ca-SGP treatment remarkably prevented the reduction of bone mass, improved cancellous bone structure and biochemical properties. Ca-SGP also significantly decreased the serum contents of TRAP, Cath-K, MMP-9, DPD, CTX-1, Ca, and P. Mechanism investigation revealed that Ca-SGP significantly increased the OPG/RANKL ratio in mRNA expression, protein expression and serum content. Further research suggested that NF-κB signaling pathways were inhibited by suppressing the mRNA and protein expressions of NFATc1 and TRAF6, diminishing the mRNA expression and phosphorylation of NF-κB p65, three key transcription factors in NF-κB pathways. These results suggest that Ca-SGP can improve osteoporosis by inhibiting bone resorption via suppressing the activation of osteoclastogenesis related NF-κB pathways.

Plasma and cellular pharmacokinetic considerations for the development and optimization of antitumor block copolymer micelles.

INTRODUCTION: Clinical application of anticancer drugs is often limited by poor pharmacokinetic profile. The biocompatible and/or biodegradable block copolymer micelles (BCMs) can improve the pharmacokinetic behavior of drugs, thus enhancing antitumor effect. However, there are still many problems that needed to be solved before there is a wide clinical application of BCMs. AREAS COVERED: Micelles have been quickly developed recently to deliver hydrophobic antitumor drugs specifically. However, the final therapeutic effect of BCMs is often challenged by many factors in vivo from both plasma and cellular pharmacokinetic view: i) inefficient transport from administration site to tumor tissue; ii) poor penetration into tumor mass; iii) inadequate accumulation in tumor cell; and iv) insufficient intracellular/subcellular release in cells. This review emphasized on the newest methods and solutions based on the main challenges of BCMs application in vivo, and the new problems caused by these methods are also discussed. EXPERT OPINION: Different strategies and designs of BCMs can help solve problems in each key step respectively. However, overemphasis on one aspect will result in problems on others. Therefore, a comprehensive consideration is urgently needed to integrate the advantages of each strategy and overcome the disadvantages. Only with thorough understanding and scientific assessments, the desired BCMs are expected to be applied in clinical treatments.

Phosphorylated Peptides from Antarctic Krill (Euphausia superba) Prevent Estrogen Deficiency Induced Osteoporosis by Inhibiting Bone Resorption in Ovariectomized Rats.

In the current study, we investigated the improvement of phosphorylated peptides from Antarctic krill Euphausia superba (PP-AKP) on osteoporosis in ovariectomized rats. PP-AKP was supplemented to ovariectomized Sprague-Dawley rats for 90 days. The results showed that PP-AKP treatment remarkably prevented the reduction of bone mass and improved cancellous bone structure and biochemical properties. PP-AKP also significantly decreased serum contents of tartrate-resistant acid phosphatase (TRACP), cathepsin K (Cath-k), matrix metalloproteinases-9 (MMP-9), deoxypyridinoline (DPD), C-terminal telopeptide of collagen I (CTX-1), Ca, and P. Mechanism investigation revealed that PP-AKP significantly increased the osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio in mRNA expression, protein expression, and serum content. Further research suggested that NF-κB signaling pathways were inhibited by suppressing the mRNA and protein expressions of nuclear factor of activated T-cells (NFATc1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), diminishing the mRNA expression and phosphorylation of nuclear factor κB p65 (NF-κB p65), three key transcription factors in NF-κB pathways. These results suggest that PP-AKP can improve osteoporosis by inhibiting bone resorption via suppressing the activation of osteoclastogenesis related NF-κB pathways.

Synthesis, physical properties and self-assembly behavior of azole-fused pyrene derivatives.

A novel selenadiazole-fused pyrene derivative PySe was successfully synthesized and characterized. Its single structure is almost planar and adopts a sandwich-herringbone packing model. The self-assembly behaviors based on compound PySe and its analogue thiadiazole-fused pyrene derivative PyS were studied in detail and the as-formed nanostructures were fully characterized by means of UV-vis absorption, emission spectra, X-ray diffraction, field emission SEM and TEM. We attribute the bathochromic shift absorption and emission spectra of PyS and PySe in aqueous solution to the formation of J-type aggregation. In addition, our investigation demonstrated that the shape and size of the as-prepared nanostructures could be tuned by different chalcogen analogues and the volume ratio of water to organic solvent.

Synthesis and characterization of a novel polydepsipeptide contained tri-block copolymer (mPEG-PLLA-PMMD) as self-assembly micelle delivery system for paclitaxel.

A series of biodegradable polydepsipeptides based new triblock copolymers, poly (ethylene glycol)-poly(L-lactide)-poly(3(S)-methyl-morpholine-2,5-dione) (mPEG-PLLA-PMMD) have been synthesized and characterized as self-assembly micelle delivery system for paclitaxel (PTX). Compared to the mPEG(2000)-PLLA(2000) diblock copolymers, the triblock copolymers present more benefits such as lower CMC value, positive-shifted zeta potential, better drug loading efficiency and stability. Among the triblock polymers, mPEG(2000)-PLLA(2000)-PMMD(1400) micelles present low cytotoxicity and promote the anti-cancer activity of PTX on A-549 and HCT-116cells. In addition, mPEG(2000)-PLLA(2000)-PMMD(1400) micelles prolongs the circulation time of PTX in rat after i.v. injection (5 mg/kg) than that of mPEG(2000)-PLLA(2000) micelles and Taxol. The half life (t(1/2ß)), mean residence time (MRT), AUC(0-∞) and clearance (CL) for PTX-loaded mPEG(2000)-PLLA(2000)-PMMD(1400) micelles are determined to be 1.941 h, 2.683 h, 5.220 µg/m Lh (1.8-fold to mPEG(2000)-PLLA(2000) group), 0.967 L/h kg(-1), respectively. In conclusion, mPEG(2000)-PLLA(2000)-PMMD(1400) copolymer could be developed as one of the promising vectors to anti-cancer agents for chemotherapeutics.