No Causal Association Between Inguinal Hernia and Aortic Aneurysm Using Mendelian Randomization Analysis.

Aortic aneurysm (AA) is a serious disease that affects the aging population worldwide. Potential risk or associated factors, such as inguinal hernia, have been suggested by conventional studies. In the present study, summary statistics data for the associations of inguinal hernia were derived from a large genome-wide association study including 18,791 inguinal hernia cases and 93,955 controls in the UK Biobank. Corresponding data of AA were extracted from FinnGen, comprising 7603 cases and 317,899 controls in Finland. The causal association was assessed using Mendelian Randomization-Egger, weighted median, and inverse variance weighting methods, and compared with observational estimates previously published. Our analysis found no convincing causal effect between genetically predicted inguinal hernia and the risk of AA (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 0.85-1.31, P = .65), abdominal aortic aneurysm (AAA, OR = 1.15, 95% CI = 0.92-1.46, P = .22), and thoracic aortic aneurysm (TAA, OR = 1.05, 95% CI = 0.85-1.30, P = .67). The results are in contrast to previous observational evidence suggesting a potentially common causal association between inguinal hernia and AA. Further research is needed to better understand the interplay between risk factors and their impact on aneurysm development.

Size-dependence of the skin penetration of andrographolide nanosuspensions: In vitro release-ex vivo permeation correlation and visualization of the delivery pathway.

Particle size is a key parameter to determine the capacity of nanoparticles to overcome the skin barrier; however, such effect and the possible mechanism remain only partially understood for nanosuspensions. In this work, we examined the skin delivery performance of andrographolide nanosuspensions (AG-NS) ranging in diameter from 250 nm to 1000 nm and analyzed the role of particle size in influencing their ability of skin penetration. The AG-NS with particle sizes of about 250 nm (AG-NS250), 450 nm (AG-NS450), and 1000 nm (AG-NS1000) were successfully prepared by ultrasonic dispersion method and characterized by transmission electron microscopy. The drug release and penetration via the intact and barrier-removed skin were compared by the Franz cell method, and the related mechanisms were probed using laser scanning confocal microscopy (LSCM) via visualization of penetration routes and histopathological study via observation of structural change of the skin. Our finding revealed that drug retention in the skin or its sub-layers was increased with the reduction of particle size, and the drug permeability through the skin also exhibited an obvious dependence on the particle size from 250 nm to 1000 nm. The linear relationship between the in vitro drug release and ex vivo permeation through the intact skin was well established among different preparations and in each preparation, indicating the skin permeation of the drug was mainly determined by the release process. The LSCM indicated that all these nanosuspensions could deliver the drug into the intercellular lipid space, as well as block the hair follicle in the skin, where a similar size dependence was also observed. The histopathological investigation showed that the formulations could make the stratum corneum of the skin loose and swelling without severe irritation. In conclusion, the reduction of particle size of nanosuspension would facilitate topical drug retention mainly via the modulation of drug release.

Nonporous versus Mesoporous Bioinspired Polydopamine Nanoparticles for Skin Drug Delivery.

The use of polydopamine-based bioinspired nanomaterials has shed new light on advanced drug delivery arising from their efficient surface functionalization. More recently, the polydopamine self-assemblies formed in two different modalities, i.e., nonporous and mesoporous nanoparticles, have begun to attract attention due to their expedient and versatile properties. However, their possibility for use in dermal drug delivery for local therapy, as well as their interaction with the skin, has not yet been demonstrated. Our study aimed to compare and explore the feasibility of the self-assembled nonporous polydopamine nanoparticles (PDA) and mesoporous polydopamine nanoparticles (mPDA) for local skin drug delivery. The formation of the PDA and mPDA structures was confirmed by the UV-vis-NIR absorption spectrum, the Fourier transform infrared spectroscopy, and the nitrogen adsorption/desorption isotherms. Using retinoic acid (RA) as the model drug, their effects on drug loading, release, photostability, skin penetration, and radical scavenging were investigated. Laser scanning confocal microscopy (LSCM) and hematoxylin and eosin (H&E) were introduced to probe their delivery routes and possible interaction with the skin. The results indicated that both PDA and mPDA could reduce the photodegradation of RA, and mPDA showed significantly better radical scavenging activity and drug loading capacity. The ex vivo permeation study revealed that both PDA and mPDA significantly enhanced the delivery of RA into the deep skin layers by comparison with the RA solution, in which follicular and intercellular pathways existed, and alteration in the structure of stratum corneum was observed. In light of drug loading capacity, size controllability, physical stability, as well as radical scavenging activity, mPDA was more preferable due to the improvement of these factors. This work demonstrated the feasibility and promising application of PDA and mPDA nanoparticles for dermal drug delivery, and the comparative concept of these two types of biomaterials can provide implications for their use in other fields.

ZIF-8 integrated with polydopamine coating as a novel nano-platform for skin-specific drug delivery.

Metal-organic frameworks (MOFs) are highly promising as a novel class of drug delivery carriers; however, there are few reports about their application in nanoparticle-based formulations for dermal administration. In this work, we developed a novel kind of nanoparticular system based on zeolitic imidazolate framework-8 (ZIF-8) and polydopamine (PDA) modification for improving the dermal delivery of 5-fluorouracil (5-FU). The structures and properties of the prepared nanoparticles were characterized using a variety of analytical methods. Their ex vivo delivery performance in the skin was investigated using Franz cells, and the underlying mechanisms were studied via confocal laser scanning microscopy (CLSM) and hematoxylin-eosin (HE) experiments which were employed to probe the penetration pathway and the interaction between nanoparticles and the skin. The results revealed that both 5-FU@ZIF-8 and ZIF-8@5-FU@PDA had an enhancement effect on the deposition of 5-FU in the skin, and the surface coating of PDA could further reduce drug permeation across the skin, especially in the case of impaired skin, in comparison with the drug solution. The CLSM study using rhodamine 6G as the fluorescent probe to mimic 5-FU indicated that ZIF-8 and ZIF-8@PDA could deliver their payloads into the skin via two pathways, i.e., intercellular and follicular ones, and the follicular route was shown to be particularly important for ZIF-8@PDA, in which the drug and carrier were co-delivered into the skin as an intact particle. This study provides evidence for using ZIF-8 and PDA modification for skin-specific drug delivery and offers an effective avenue to develop novel nanoplatforms for dermal application to treat skin diseases.

Light-related activities of metal-based nanoparticles and their implications on dermatological treatment.

Metal-based nanoparticles (MNPs) represent an emerging class of materials that have attracted enormous attention in many fields. By comparison with other biomaterials, MNPs own unique optical properties which make them a potential alternative to conventional therapeutic agents in medical applications. Especially, owing to the easy access to the skin, the use of MNPs based on their optical properties has gained importance for the treatment of a variety of skin diseases. This review provides an insight into the different optical properties of MNPs, including photoprotection, photocatalysis, and photothermal, and highlights their implications in treating skin disorders, with a special emphasis on their use in infection control. Finally, a perspective on the safety concern of MNPs for dermatological use is discussed and analyzed. The information gathered and presented in this review will help the readers have a comprehensive understanding of utilizing the photo-triggered activity of MNPs for the treatment of skin diseases.

Probing Pharmaceutical Strategies to Promote the Skin Delivery of Asiatic Acid from Hydrogels: Enhancement Effects of Organic Amine Counterions, Chemical Enhancers, and Microneedle Pretreatment.

Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation for AA and improve its skin penetration by various penetration enhancement methods. Four kinds of hydrogel bases were selected to prepare the AA hydrogel, in which different organic amines and chemical enhancers were incorporated in combination with microneedle pretreatment. The results showed that AA had good release profiles in the presence of hyaluronic acid as the hydrogel base and organic amines as the counter-ions. Diethylamine and Span 80 could promote drug penetration into the skin, and pretreatment with microneedles could further increase the drug permeability. In conclusion, the optimized hyaluronic acid hydrogel has great potential for use in the topical delivery of AA, and its penetration via the skin can be further improved by different pharmaceutical approaches.

Renoprotective effect of Tanshinone IIA against kidney injury induced by ischemia-reperfusion in obese rats.

OBJECTIVE: Obesity enhances the frequency and severity of acute kidney injury (AKI) induced by renal ischemia-reperfusion (IR). Tanshinone IIA (TIIA) pre-treatment was used to alleviate renal injury induced by renal IR, and whether TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats was examined. METHODS: Male rates were fed a high-fat diet for 8 weeks to generate obesity, followed by 30 min of kidney ischemia and 24 h reperfusion induced AKI. The male obese rates were given TIIA (5 mg/kg.d, 10 mg/kg.d, and 20 mg/kg.d) for 2 weeks before renal IR. RESULTS: TIIA alleviated the pathohistological injury and apoptosis induced by IR. In addition, TIIA improved renal function, inflammatory factor, and balance of oxidation and antioxidation in obese rats after renal IR. At the same time, TIIA can inhibit cell apoptosis by improving mitochondrial function through the PI3K/Akt/Bad pathway. Mitochondrial dysfunction was supported by decreasing intracellular ATP, respiration controlling rate (RCR), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex enzymes, and by increasing ROS, the opening of mitochondrial permeability transition pore (mPTP), and the mtDNA damage. The injury to mitochondrial dynamic function was assessed by decreasing Drp1, and increasing Mfn1/2; and the injury of mitochondrial biogenesis was assessed by decreasing PGC-1, Nrf1, and TFam. CONCLUSIONS: Renal mitochondrial dysfunction occurs along with renal IR and can induce renal cell apoptosis. Obesity can aggravate apoptosis. TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats.

Elucidating the particle size effect of andrographolide suspensions on their IVIVC performance in oral absorption.

The study aimed to explore the size effect on the in vitro-in vivo correlation (IVIVC) in the oral absorption of andrographolide nanosuspensions (Ag-NS). Ag-NS with controllable particle sizes were prepared by ultrasonic dispersion method, and the formulation and process parameters were optimized through single factor experiments using mean particle size, polydispersity index, and stability as evaluation indicators. The morphology of Ag-NS was observed by scanning electron microscopy (SEM), and the crystalline state of the nanosuspensions was characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The dissolution tests were carried out with the paddle method in two different mediums simulating the pH conditions in intestinal fluid (pH 6.8) and gastric fluid (pH 1.2), respectively. The pharmacokinetic behaviors were investigated in rats after oral administration, and a deconvolution approach was introduced to determine the correlation between in vitro dissolution and in vivo absorption (IVIVC). The formulation with the use of lecithin and PEG-800 as stabilizers showed its potential in the size-controllable preparation of Ag-NS. Via altering the ultrasonication amplitude and time, three Ag-NS suspensions with three particle sizes, i.e., Ag-NS 250 (249.8 ± 1.3 nm), Ag-NS 450 (485.2 ± 3.7 nm), Ag-NS 1000 (1015 ± 36.1 nm) were prepared. Their morphological and crystal characteristics were not changed during the size reduction process, but both of their in vitro dissolution and in vivo absorption were improved. Relatively better IVIVC performance was observed with the in vitro dissolution data at pH 6.8 (r > 0.9). With the reduction of particle size, the in vivo absorption fraction was more closed to the level of the in vitro dissolution. In conclusion, the decrease in particle size would improve the dissolution and absorption of Ag-NS, and also affect their IVIVC performance. The study would facilitate the design and quality control of Ag-NS in terms of particle size and dissolution specifications.

Synergistic enhancement on flexible solid-state supercapacitor based on redox-active Fe3+ions/natural spidroin modified vertically aligned carbon nanotube arrays.

The conductive skeleton and aligned carbon nanotube array (CNTA) structure can greatly shorten the ion transfer path and promote the charge transfer speed, which makes the CNTA an ideal electrode material for energy storage application. However, poor mechanical stability and low specific capacitance greatly impede its practical utilization. Here, we introduce a promising flexible electrode material based on the natural spider silk protein (SSP) modified CNTA(SSP/CNTA) with improved hydrophilicity and mechanical flexibility. The redox-active Fe3+doped SSP/CNTA flexible solid-state supercapacitor (FSSC) device with superior energy storage performance was assembled in a symmetric 'sandwich-type' structure. The synergetic interaction between Fe3+ions and the SSP are proved to greatly enhance the electrochemical performance especially the long-term cyclic stability. The Fe3+doped SSP/CNTA FSSCs device achieves an ultra-high volumetric capacitance of 4.92 F cm-3at a sweep speed of 1 mV s-1. Meanwhile it exhibited an excellent cycling stability with an increased capacitance by 10% after 10 000 charge-discharge cycles. As a control, a Fe3+doped CNTA composite device without SSP will lose over 74% of the capacitance after 10 000 cycles. The energy storage mechanism analysis confirms the dominated capacitive behavior of the device, which explained a considerable power density and rate performance. Our method thus provides a promising strategy to build up highly-efficient redox-enhanced FSSCs for next generation of wearable and implantable electronics.

A possible new activator of PI3K-Huayu Qutan Recipe alleviates mitochondrial apoptosis in obesity rats with acute myocardial infarction.

Obesity, which has unknown pathogenesis, can increase the frequency and seriousness of acute myocardial infarction (AMI). This study evaluated effect of Huayu Qutan Recipe (HQR) pretreatment on myocardial apoptosis induced by AMI by regulating mitochondrial function via PI3K/Akt/Bad pathway in rats with obesity. For in vivo experiments, 60 male rats were randomly divided into 6 groups: sham group, AMI group, AMI (obese) group, 4.5, 9.0 and 18.0 g/kg/d HQR groups. The models fed on HQR with different concentrations for 2 weeks before AMI. For in vitro experiments, the cardiomyocytes line (H9c2) was used. Cells were pretreated with palmitic acid (PA) for 24 h, then to build hypoxia model followed by HQR-containing serum for 24 h. Related indicators were also detected. In vivo, HQR can lessen pathohistological damage and apoptosis after AMI. In addition, HQR improves blood fat levels, cardiac function, inflammatory factor, the balance of oxidation and antioxidation, as well as lessen infarction in rats with obesity after AMI. Meanwhile, HQR can diminish myocardial cell death by improving mitochondrial function via PI3K/Akt/Bad pathway activation. In vitro, HQR inhibited H9c2 cells apoptosis, improved mitochondrial function and activated the PI3K/Akt/Bad pathway, but effects can be peripeteiad by LY294002. Myocardial mitochondrial dysfunction occurs following AMI and can lead to myocardial apoptosis, which can be aggravated by obesity. HQR can relieve myocardial apoptosis by improving mitochondrial function via the PI3K/Akt/Bad pathway in rats with obesity.

Biopsy Forceps-Assisted Loop Snare Technique for Complex Retrieval of Inferior Vena Cava Filter.

INTRODUCTION: Severe tilt with embedded hooks is a common obstacle to successful inferior vena cava (IVC) filter retrieval. METHODS: Disposal biopsy forceps were used to remodel the filter hook in the center position to release the embedded hook from the caval wall. RESULTS: The biopsy forceps-assisted loop snare technique was successfully used to retrieve filters with hooks embedded in the IVC wall. CONCLUSION: The biopsy forceps-assisted loop snare technique we present here offers a new solution for the complex retrieval of IVC filters. This technique may prove useful in cases where standard techniques at filter retrieval fail.

Vascular Endothelial Function as a Valid Predictor of Variations in Pulmonary Function in T2DM Patients Without Related Complications.

To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group (P < 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) (P < 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO (P < 0.05) and correlated negatively with endothelin-1 (ET-1) (P < 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c (P < 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration (P < 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration (P < 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index (P < 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03575988.

Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats.

BACKGROUND: Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. METHODS: Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. After 24 h of reperfusion, the rats were anaesthetized, the blood were fetched from the abdominal aorta and kidney were fetched from abdominal cavity, then related indicators were examined. RESULTS: TIIA combined with CsA can alleviate the pathohistological injury and apoptosis induced by renal IR in myocardial cells. TIIA combined with CsA improved cardiac function after renal ischemia (30 min)-reperfusion (24 h) in obese rats. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes. The injury of mitochondrial dynamic function was assessed by decrease in dynamin-related protein 1 (Drp1), and increases in mitofusin1/2 (Mfn1/2), and mitochondrial biogenesis injury was assessed by decreases in PPARγ coactivator-1-α (PGC-1), nucleo respiratory factor1 (Nrf1), and transcription factor A of mitochondrial (TFam). CONCLUSION: We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Improved wettability and enhanced ionic transport in highly porous CNT sponge.

We investigated the effect of an electric treatment on the wettability of aqueous solution on carbon nanotubes (CNT) and ion transport behaviors in superhydrophobic porous carbon nanotube sponges (CNTS). This electric activation treatment where an electric voltage was applied across highly porous CNT sponge induced an electrowetting effect. This effect significantly reduced interfacial tensions between CNT sidewalls and aqueous liquids. Meanwhile, polar functional groups were also introduced on CNTs. Both electrowetting effect and polar functional groups greatly improved the wettability of aqueous solutions on CNT sidewalls. After the electric treatment, we observed a dramatic increase in the overall rate of ion flow across porous CNT sponges. The formation of solution channels during the electric treatment is responsible for the enhanced ionic transport in porous CNT sponges. The overall rate of ion flow increased with the increases in electric treatment time and voltage. The crucial role of electric treatment parameters in the ion transport provides a new strategy for precisely controlling the ion transport across CNT sponges by tuning electric treatment time or voltage. Importantly, the good wettability of aqueous solution on CNT sidewalls greatly increased the effective surface area of CNT sponges and thus significantly improved the performance of CNTS-based supercapacitors after the electric treatment.