Frontiers of Plant-derived Exosomes from Research Methods to Pharmaceutical Applications in Plant-based Therapeutics

Exosomes have emerged as critical mediators of intercellular communication and various physiological processes between cells and their environment. These nano-sized vesicles have been extensively investigated and confirmed to exhibit multifunctionality in animal systems. In particular, they participate in intercellular signaling, influence disease progression, and exhibit biological activity. However, Plant-Derived Exosomes (PDEs), especially therapeutic PDEs, have received relatively limited attention in the past few decades. Recent studies have demonstrated that PDEs are involved in signaling molecule transport in addition to intercellular communication, as they serve as functional molecules in the cellular microenvironment. This characteristic highlights the immense potential of PDEs for a wide array of applications, including antioxidation, anti-inflammation, tumour cell elimination, immune modulation, and tissue regeneration. In addition, PDEs hold substantial promise as efficient drug carriers, enhancing the stability and bioavailability of therapeutic agents and consequently enabling targeted delivery to specific cells or tissues. Therefore, PDEs may serve as effective tools for drug delivery and the treatment of various diseases. This comprehensive review provides an overview of recent studies on therapeutic PDEs, focusing on their extraction, isolation, characterization methods, biological activities, and application prospects. It summarises the research progress of exosome-like nanovesicles derived from medicinal plants, with a specific emphasis on traditional Chinese medicine, and highlights their importance in disease treatment and nanoparticle delivery. The main objective is to accelerate the clinical translation of these nanovesicles while providing novel approaches and methodologies for the research and development of innovative drugs.

Network meta-analysis of multiple doses of vonoprazan for the treatment of erosive esophagitis.

Aim: 20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Materials & methods: Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. Results: VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Conclusion: Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.

A Lamb Waves Based Ultrasonic System for the Simultaneous Data Communication, Defect Inspection, and Power Transmission.

Lamb-wave-based structural health monitoring (SHM) has attracted extensive attention in recent years. This article aims to realize the functions of data communication, defect detection, and energy transmission through piezoelectric transducers. In this work, the S0 mode at 500 kHz and the A0 mode at 150 kHz are selected as the carrier waves and the optimized excitation frequencies are determined through analytical investigation and frequency sweeping experiments. The S0 mode is used for data communication and defect inspection due to the high excitation frequency and low dispersion properties. A single piezoelectric sensing element acts as the transmitter and a nine-element piezoelectric transducer array (PTA) is the receiver. Their roles exchange in terms of energy transmission based on the A0 mode. Simultaneous data communication and energy transmission are achieved based on the frequency division multiplexing (FDM) strategy. After performing a matched filter on the received signals, the digital data information can be recovered under the interference of the energy transmission signal. The synthetic aperture imaging technology (SAFT) is adopted for accurately locating defects on aluminum plates. In terms of energy transmission, a constructive interference performance is achieved by the transducer array with a transmitted power of 3.81 mW. This system has great potential for health monitoring of the enclosed structure by eliminating the cumbersome wires for powering and communication.

Enhanced oral delivery and anti-gastroesophageal reflux activity of curcumin by binary mixed micelles.

The aim of this study was to improve the solubility, oral bioavailability, and anti-gastroesophageal reflux activity of curcumin (CM) by preparing two CM-loaded, novel, binary mixed micelles (CM-M). The two CM-M were prepared by ethanol thin-film hydration method. One (CM-T) was prepared using D-alpha-tocopheryl polyethylene glycol 1000 succinate and Solutol®HS15, and the other (CM-F) was prepared using Pluronic®F127 and Solutol®HS15. The entrapment efficiency and drug loading of CM-T were 83.61 ± 0.54% and 2.20 ± 0.65%, respectively, which were lower than those of CM-F (88.66 ± 0.12% and 1.47 ± 0.26%, respectively). TEM results demonstrated that CM-T and CM-F were homogeneous and spherical. The permeability of CM delivered via CM-T and CM-F was enhanced across a Caco-2 cell monolayer, and CM-T and CM-F showed a 5.24- and 4.76-fold increase in relative oral bioavailability, respectively compared with free CM. In addition, the in vivo anti-gastroesophageal reflux study showed that CM-T and CM-F achieved higher anti-gastroesophageal reflux efficacy compared with free CM. Collectively, these findings were indicative of an oral micelle formulation of CM with increased solubility, oral bioavailability, and anti-gastroesophageal reflux activity.

Airway hyperresponsiveness induced by repeated esophageal infusion of HCl in guinea pigs.

Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days. In addition, contractile responses to acetylcholine (ACh), KCl, electrical field stimulation, and extracellular Ca(2+) were greater in guinea pigs infused with HCl compared with control groups. The L-type voltage-dependent Ca(2+) channels (L-VDCC) blocker, nicardipine, significantly inhibited ACh- and Ca(2+)-enhanced BSM contractions in guinea pigs infused with HCl. The Rho-kinase inhibitor, Y27632, attenuated ACh-enhanced BSM contractions in guinea pigs infused with HCl. Moreover, mRNA and protein expressions for muscarinic M2 and M3 receptors, RhoA, and L-VDCC in BSM were detected by real-time PCR and Western blot. Expressions of mRNA and protein for muscarinic M3 receptors, RhoA, and L-VDCC were greater than in BSM of HCl-infused guinea pigs, whereas levels of muscarinic M2 receptors were unchanged. We demonstrate that acid infusion to the lower esophagus and, subsequently, microaspiration into the respiratory tract in guinea pigs leads to airway hyperresponsiveness and overactive BSM. Functional and molecular results indicate that overactive BSM is the reason for enhancement of extracellular Ca(2+) influx via L-VDCC and Ca(2+) sensitization through Rho-kinase signaling.

Preparation and evaluation of berberine alginate beads for stomach-specific delivery.

The purpose of this research was to prepare floating calcium alginate beads of berberine for targeting the gastric mucosa and prolonging their gastric residence time. The floating beads were prepared by suspending octodecanol and berberine in sodium alginate (SA) solution. The suspension was then dripped into a solution of calcium chloride. The hydrophobic and low-density octodecanol enhanced the sustained-release properties and floating ability of the beads. The bead formulation was optimized for different weight ratios of octodecanol and SA and evaluated in terms of diameter, floating ability and drug loading, entrapment and release. In vitro release studies showed that the floating and sustained release time were effectively increased in gastric media by addition of octodecanol. In vivo studies with rats showed that a significant increase in gastric residence time of beads had been achieved.

Electrical characteristics and photocurrent spectral response of Si nanowires p-i-n junctions.

P-i-n junctions were fabricated along Si nanowires (SiNWs) via the conventional top-down approach using optical lithography. Each device comprises 500 identical SiNWs connected in parallel, and each SiNW has triangular cross-section with dimensions of ~6 nm (base) by ~8 nm (height). The photodiodes exhibit very good rectifying electrical characteristics with a low reverse bias current of ~0.2 fA per SiNW. The photocurrent spectral response exhibits three peaks between 400 nm to 700 nm, which arise due to local optical field enhancement associated with diffraction by the periodic SiNW array and interference in an air/SiO2/Si cavity.