Natural Products with Potential Effects on Hemorrhoids: A Review.

Hemorrhoid disease is a common anorectal disorder affecting populations worldwide, with high prevalence, treatment difficulties, and considerable treatment costs. Compared to other treatment options, medical therapy for hemorrhoids offers minimal harm, more dignity to patients, and is more economical. Unfortunately, there are few chemical hemorrhoid medications available clinically, which makes the search for efficacious, cost-effective, and environmentally friendly new medication classes a focal point of research. In this context, searching for available natural products to improve hemorrhoids exhibits tremendous potential. These products are derived from nature, predominantly from plants, with a minor portion coming from animals, fungi, and algae. They have excellent coagulation pathway regulation, anti-inflammatory, antibacterial, and tissue regeneration activities. Therefore, we take the view that they are a class of potential hemorrhoid drugs, prevention products, and medication add-on ingredients. This article first reviews the factors contributing to the development of hemorrhoids, types, primary symptoms, and the mechanisms of natural products for hemorrhoids. Building on this foundation, we screened natural products with potential hemorrhoid improvement activity, including polyphenols and flavonoids, terpenes, polysaccharides, and other types.

CX3CL1 and its receptor CX3CR1 interact with RhoA signaling to induce paclitaxel resistance in gastric cancer.

C-X3-C motif chemokine ligand 1 (CX3CL1) is a transmembrane protein, and the membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1/CX3CR1 axis induces many cellular responses relevant to cancer, such as proliferation, migration, invasion, and apoptosis resistance. Here we attempt to elucidate whether CX3CL1/CX3CR1 is associated with paclitaxel (PTX) resistance in gastric cancer (GC). The Gene Expression Omnibus database was queried to screen for differentially expressed genes in GC cells caused by drug resistance, and CX3CL1 was selected as a candidate. CX3CL1 was overexpressed in PTX-resistant cells and tissues. CX3CL1 loss sensitized GC cells to PTX, promoted apoptosis and DNA damage, and inhibited cell proliferation, migration, and invasion. CX3CR1 reversed the ameliorative effect of CX3CL1 silencing on PTX sensitivity in GC cells. The promotion of PTX resistance by CX3CL1/CX3CR1 was inhibited by impairment of the small GTPase Ras homolog gene family member A (RhoA) pathway in vitro and in vivo. These findings indicate that the CX3CL1/CX3CR1 expedites PTX resistance through the RhoA signaling in GC cells.

A Symmetric-Actuating Linear Piezoceramic Ultrasonic Motor Capable of Producing a Scissoring Effect.

Conventionally, to produce a linear motion, one motor's stator is employed to drive one runner moving forward or backward. So far, there is almost no report of one electromechanical motor or piezoelectric ultrasonic motor that can directly generate two symmetrical linear motions, while this function is desired for precise scissoring and grasping in the minimally invasive surgery field. Herein, we report a brand-new symmetric-actuating linear piezoceramic ultrasonic motor capable of generating symmetrical linear motions of two outputs directly without additional mechanical transmission mechanisms. The key component of the motor is an (2 × 3) arrayed piezoceramic bar stator operating in the coupled resonant mode of the first longitudinal (L1) and third bending (B3) modes, leading to symmetric elliptical vibration trajectories at its two ends. A pair of microsurgical scissors is used as the end-effector, demonstrating a very promising future for high-precision microsurgical operations. The sliders of the prototype show the following features: (a) symmetrical, fast relative moving velocity (~1 m/s) outward or inward simultaneously; (b) high step resolution (40 nm); and (c) high power density (405.4 mW/cm3) and high efficiency (22.1%) that are double those of typical piezoceramic ultrasonic motors, indicating the full capacity of symmetric-actuating linear piezoceramic ultrasonic motor working in symmetric operation principle. This work also has enlightening significance for future symmetric-actuating device designs.

Kirigami-Origami-Inspired Lead-Free Piezoelectric Ceramics.

Kirigami- and oirigami-inspired techniques have emerged as effective strategies for material structure design; however, the use of these techniques is usually limited to soft and deformable materials. Piezoelectric ceramics, which are typical functional ceramics, are widely used in electronic and energy devices; however, the processing options for piezoelectric ceramics are limited by their brittleness and feedstock viscosity. Here, a design strategy is proposed for the preparation of lead-free piezoelectric ceramics inspired by kirigami/origami. This strategy involves direct writing printing and control over the external gravity during the calcination process for the preparation of curved and porous piezoelectric ceramics with specific shapes. The sintered BaTiO3 ceramics with curved geometries produced using this strategy exhibit a high piezoelectric constant (d33 = 275 pC N-1 ), which is 45% higher than that of conventionally sintered sheet ceramics. The curved structure of the ceramics is well-suited for use in the human body and it was determined that these curved ceramics can detect pulse signals. This strategy can be applied in the large-scale and low-cost production of other piezoelectric ceramics with various curved shapes and provides a new approach for the preparation of complex-shaped ceramics.

Designing Artificial Vibration Modes of Piezoelectric Devices Using Programmable, 3D Ordered Structure with Piezoceramic Strain Units.

Piezoelectric ceramic devices, which utilize multifarious vibration modes to realize electromechanical coupling and energy conversions, are extensively used in high-technological fields. However, the excitation of basic modes is mainly subjected to natural eigenfrequency of ceramic devices, which is related to the structure and material parameters. Herein, inspired by metamaterial theory, a programmable, 3D ordered structure with piezoceramic strain units (3D OSPSU) is developed to artificially generate basic modes in a broad frequency band other than only in narrow eigenfrequency. A (2 × 2 × 2) arrayed, co-fired, multilayer 3D OSPSU is painstakingly designed and fabricated for generating basic modes, such as flexural, extension, shear, torsion, and even coupled modes at nonresonance. To validate the 3D OSPSU method, a five-degree-of-freedom micro-nano actuating platform based on only one co-fired multilayer ceramic is constructed. The proposed methodology provides a new paradigm for creating extraordinary material properties of piezoelectric ceramics and will inspire brand-new piezoelectric device designs.

Designing electromechanical metamaterial with full nonzero piezoelectric coefficients.

Designing topological and geometrical structures with extended unnatural parameters (negative, near-zero, ultrahigh, or tunable) and counterintuitive properties is a big challenge in the field of metamaterials, especially for relatively unexplored materials with multiphysics coupling effects. For natural piezoelectric ceramics, only five nonzero elements in the piezoelectric matrix exist, which has impeded the design and application of piezoelectric devices for decades. Here, we introduce a methodology, inspired by quasi-symmetry breaking, realizing artificial anisotropy by metamaterial design to excite all the nonzero elements in contrast to zero values in natural materials. By elaborately programming topological structures and geometrical dimensions of the unit elements, we demonstrate, theoretically and experimentally, that tunable nonzero or ultrahigh values of overall effective piezoelectric coefficients can be obtained. While this work focuses on generating piezoelectric parameters of ceramics, the design principle should be inspirational to create unnatural apparent properties of other multiphysics coupling metamaterials.

Catechol-O-Methyltransferase and UDP-Glucuronosyltransferases in the Metabolism of Baicalein in Different Species.

BACKGROUND: Baicalein is the major bioactive flavonoid in some herb medicines and dietary plants; however, the detailed metabolism pathway of its major metabolite oroxylin A-7-O-ß-D-glucuronide in human was not clear. It was important to illustrate the major metabolic enzymes that participate in its elimination for the clinic use of baicalein. OBJECTIVES: We first revealed a two-step metabolism profile for baicalein and illustrated the combination of catechol-O-methyltransferase (COMT) and uridine diphosphate-glucuronosyltransferases (UGTs) in drug metabolism, further evaluated its bioactivity variation during drug metabolism. METHODS: The metabolism profiles were systematically characterized in different human biology preparations; after then, the anti-inflammatory activities of metabolites were evaluated in LPS-induced RAW264.7 cell. RESULTS: The first-step metabolite of baicalein was isolated and identified as oroxylin A; soluble-bound COMT (S-COMT) was the major enzyme responsible for its biotransformation. Specially, position 108 mutation of S-COMT significantly decreases the elimination. Meantime, oroxylin A was rapidly metabolized by UGTs, UGT1A1, -1A3, -1A6, -1A7, -1A8, -1A9, and -1A10 which were involved in the glucuronidation. Considerable species differences were observed with 1060-fold K m (3.05 ± 1.86-3234 ± 475 µM) and 330-fold CLint (5.93-1973 µL/min/mg) variations for baicalein metabolism. Finally, the middle metabolite oroxylin A exhibited a potent anti-inflammatory activity with the IC50 value of 28 µM. CONCLUSION: The detailed kinetic parameters indicated that COMT provide convenience for the next glucuronidation; monkey would be a preferred animal model for the preclinical investigation of baicalein. Importantly, oroxylin A should be reconsidered in evaluating baicalein efficacy against inflammatory diseases.