Structural modification and biomechanical analysis of lumbar disc prosthesis: A finite element study.

BACKGROUND: Most ball-in-socket artificial lumbar disc implanted in the spine result in increased hypermobility of the operative level and overloading of the facet joint. METHODS: A finite element model was established and validated for the lumbar spine (L1-L5). The structure of the Mobidisc prosthesis was modified, resulting in the development of two new intervertebral disc prostheses, Movcore and Mcopro. The prostheses were implanted into the L3/L4 level to simulate total disc replacement, and the biomechanical properties of the lumbar spine model were analyzed after the operation. FINDINGS: Following the implantation of the prostheses, the mobility of operative level, peak stress of lumbar spine models, and peak stress of facet joint increased. The performance of mobility was found to be more similar between Movcore and Mobidisc. The mobility and facet joint peak stress of the Mcopro model decreased progressively with an increase in the Young's modulus of the artificial annulus during flexion, extension, and lateral bending. Among all the models, the Mcopro50 model had the mobility closest to the intact model. It showed a 3% decrease in flexion, equal range of motion in extension, a 9% increase in left lateral bending, a 7% increase in right lateral bending, and a 3% decrease in axial rotation. INTERPRETATION: The feasibility of the new intervertebral disc prostheses, Movcore and Mcopro, has been established. The Mcopro prosthesis, which features an artificial annular structure, offers significant advantages in terms of reduced mobility of the operative level and peak stress of facet joint.

Synthesis of triazole AD-1 derivatives and its mechanism of mediating DNA damage of ROS in lung cancer cells.

Based on the significant biological activities and the remarkable physical and chemical properties of 1H-1,2,3-triazole pharmacophore, we herein adopted the strategy of click chemistry to combine the triazole fragment and the unique scaffold of 25-OCH3-PPD (AD-1) to design a series of potent compounds inducing apoptosis and DNA damage. The anti-proliferative effect was verified by MTT assay and colony formation assay. DNA double-stand breaks (DSBs) were obtained by observing the nuclear focus formation and the protein expression of γ-H2AX. Cell cycle arrest was evaluated by the cycle-related proteins such as CDK2, CDK4, CDK6, Cyclin D1 and P21. Apoptosis was assessed by flow cytometry, mitochondrial membrane potential (MMP) detection and the expression of apoptosis-related proteins. Reactive oxygen species (ROS) generation was measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA) staining. According to SAR analysis, the most potent compound 6a exhibited great inhibitory effect against A549 cells, which IC50 value of 2.84 ± 0.68 µM. Furthermore, 6a remarkably induced DNA damage, cell cycle arrest and apoptosis in A549 cells. 6a treatment increased the levels of ROS. Network pharmacology and molecular docking predicted the potential signaling pathways and ligand-receptor interactions, and the results of western blotting showed that 6a inhibited the PI3K/Akt/Bcl-2 signaling pathway by decreasing PI3K and Bcl-2 and total level of Akt expression, while Bax and Cyt c were increasing in 6a-treated A549 cells. As mentioned above, 6a has a potent inhibitory effect in A549 cells through induction of DNA damage, apoptosis via ROS generation and modulation of PI3K/Akt/Bcl-2 signaling pathway.

Recent advances of honokiol：pharmacological activities, manmade derivatives and structure-activity relationship.

Honokiol (HNK) is a typical natural biphenyl polyphenol compound. It has been proven to have a wide range of biological activities, including pharmacological effects such as anti-cancer, anti-inflammatory, neuroprotective, and antimicrobial. However, due to the poor stability, water solubility, and bioavailability of HNK, HNK has not been used in clinical treatment. This article reviews the latest research on the pharmacological activity of HNK and summarizes the HNK derivatives designed and improved by several researchers. Reviewing these contents could promote the research process of HNK and guide the design of better HNK derivatives for clinical application in the future.

Improving hemocompatibility of decellularized vascular tissue by structural modification of collagen fiber.

Decellularized vascular tissue has high potential as a tissue-engineered vascular graft because of its similarity to native vessels in terms of mechanical strength. However, exposed collagen on the tissue induces blood coagulation, and low hemocompatibility is a major obstacle to its vascular application. Here we report that freeze-drying and ethanol treatment effectively modify collagen fiber structure and drastically reduce blood coagulation on the graft surface without exogenous chemical modification. Decellularized carotid artery of ostrich was treated with freeze-drying and ethanol solution at concentrations ranging between 5 and 99.5 %. Collagen fiber distance in the graft was narrowed by freeze-drying, and the non-helical region increased by ethanol treatment. Although in vitro blood coagulation pattern was similar on the grafts, platelet adhesion on the grafts was largely suppressed by freeze-drying and ethanol treatments. Ex vivo blood circulation tests also indicated that the adsorption of platelets and Von Willebrand Factor was largely reduced to approximately 80 % by ethanol treatment. These results indicate that structural modification of collagen fibers in decellularized tissue reduces blood coagulation on the surface by inhibiting platelet adhesion.

The angelica Polysaccharide: a review of phytochemistry, pharmacology and beneficial effects on systemic diseases.

Angelica sinensis is a perennial herb widely distributed around the world, and angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis. APS is one of the main active components of Angelica sinensis. A large number of studies have shown that APS has hematopoietic, promoting blood circulation, radiation resistance, lowering blood glucose, enhancing the body immunity and other pharmacological effects in a variety of diseases. However, different extraction methods and extraction sites greatly affect the efficacy of APS. In recent years, with the emerging of new technologies, there are more and more studies on the combined application and structural modification of APS. In order to promote the comprehensive development and in-depth application of APS, this narrative review systematically summarizes the effects of different drying methods and extraction sites on the biological activity of APS, and the application of APS in the treatment of diseases, hoping to provide a scientific basis for the experimental study and clinical application of APS.

Synthesis and cytotoxic evaluation of glycosyl derivatives of icaritin.

A series of glycosyl alkyl/triazol-linked icaritin derivatives have been designed and synthesised. The target glycosyl derivatives were evaluated for their anticancer activity against three human cancer cell lines. The results of preliminary anticancer tests in vitro revealed that mannose derivatives 10a-10c (100 µM) with different aliphatic chain lengths exhibited increased cytotoxicity against HepG2 and SK-OV-3 cells compared with the parent compound icaritin. The data indicated that the kind of glycosyl groups and linkers affected the anticancer potency significantly. The ADME analysis of derivatives 10a-10c was also performed.

Impact of Molecular Weight Variations in Dendrobium officinale Polysaccharides on Antioxidant Activity and Anti-Obesity in Caenorhabditis elegans.

This research investigates the impact of Dendrobium officinale polysaccharides (DOP) with different molecular weights on antioxidant effects, lifespan enhancement, and obesity reduction, utilizing both in vitro analyses and the Caenorhabditis elegans (C. elegans) model. Through a series of experiments-ranging from the extraction and modification of polysaccharides, Gel Permeation Chromatography (GPC), and analysis of composition to the evaluation of antioxidant capabilities, this study thoroughly examines DOP and its derivatives (DOP5, DOP15, DOP25) produced via H2O2-Fe2+ degradation. The results reveal a direct relationship between the molecular weight of polysaccharides and their bioactivity. Notably, DOP5, with its intermediate molecular weight, demonstrated superior antioxidant properties, significantly extended the lifespan, and improved the health of C. elegans. Furthermore, DOP15 appeared to regulate lipid metabolism by affecting crucial lipid metabolism genes, including fat-4, fat-5, fat-6, sbp-1, and acs-2. These findings highlight the potential application of DOP derivatives as natural antioxidants and agents against obesity, contributing to the development of functional foods and dietary supplements.

Three-Dimensional-Printed Spherical Hollow Structural Scaffolds for Guiding Critical-Sized Bone Regeneration.

The treatment of bone tissue defects continues to be a complex medical issue. Recently, three-dimensional (3D)-printed scaffold technology for bone tissue engineering (BTE) has emerged as an important therapeutic approach for bone defect repair. Despite the potential of BTE scaffolds to contribute to long-term bone reconstruction, there are certain challenges associated with it including the impediment of bone growth within the scaffolds and vascular infiltration. These difficulties can be resolved by using scaffold structural modification strategies that can effectively guide bone regeneration. This study involved the preparation of biphasic calcium phosphate spherical hollow structural scaffolds (SHSS) with varying pore sizes using 3D printing (photopolymerized via digital light processing). The chemical compositions, microscopic morphologies, mechanical properties, biocompatibilities, osteogenic properties, and impact on repairing critical-sized bone defects of SHSS were assessed through characterization analyses, in vitro cytological assays, and in vivo biological experiments. The results revealed the biomimetic properties of SHSS and their favorable biocompatibility. The scaffolds stimulated cell adhesion, proliferation, differentiation, and migration and facilitated the expression of osteogenic genes and proteins, including Col-1, OCN, and OPN. Furthermore, they could effectively repair a critical-sized bone defect in a rabbit femoral condyle by establishing an osteogenic platform and guiding bone regeneration in the defect region. This innovative strategy presents a novel therapeutic approach for assessing critical-sized bone defects.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Structure modification of anoplin for fighting resistant bacteria.

The emergence of bacterial resistance has posed a significant challenge to clinical antimicrobial treatment, rendering commonly used antibiotics ineffective. The development of novel antimicrobial agents and strategies is imperative for the treatment of resistant bacterial infections. Antimicrobial peptides (AMPs) are considered a promising class of antimicrobial agents due to their low propensity for resistance and broad-spectrum activity. Anoplin is a small linear α-helical natural antimicrobial peptide that was isolated from the venom of the solitary wasp Anplius samariensis. It exhibits rich biological activity, particularly broad-spectrum antimicrobial activity and low hemolytic activity. Over the past three decades, more than 40 research publications on anoplin have been made available online. This review focuses on the advancements of anoplin in antimicrobial research, encompassing its sources, characterization, antimicrobial activity, influencing factors and structural modifications. The aim is to provide assistances for the development of new antimicrobial agents that can combat bacterial resistance.

Discovery of Pesticide Candidates from Natural Plant Products: Semisynthesis and Characterization of Andrographolide-Based Esters and Study of Their Pesticidal Properties and Toxicology.

To explore the use of nonfood plant-derived secondary metabolites for plant protection, a series of ester derivatives for controlling the major migratory agricultural pests were obtained by structural modification of andrographolide, a labdane diterpenoid isolated from Andrographis paniculata. Compound Id showed good insecticidal activity against the fall armyworm Spodoptera frugiperda Smith. Compounds IIa (LC50: 0.382 mg/mL) and IIIc (LC50: 0.563 mg/mL), the acaricidal activities of which were, respectively, 13.1 and 8.9 times that of andrographolide (LC50: 4.996 mg/mL), exhibited strong acaricidal and control effects against Tetranychus cinnabarinus Boisduval. Against Aphis citricola Van der Goot, compounds IIIc and IVb displayed 3.9- and 3.7-fold pronounced aphicidal activity of andrographolide. Effects of compound Id on three protective enzymes (superoxide dismutase, peroxidase, and catalase) of S. frugiperda were also observed. The obvious differences of epidermal cuticle structures of mites treated with compound IIa were determined by scanning electron microscopy. Structure-activity relationships indicated that 14-ester derivatives of andrographolide showed potential insecticidal/acaricidal activities and can be further utilized as lead compounds.

Glucagon-like peptide-1 analogs: Miracle drugs are blooming?

Glucagon-like peptide-1 (GLP-1), secreted by L cells in the small intestine, assumes a central role in managing type 2 diabetes mellitus (T2DM) and obesity. Its influence on insulin secretion and gastric emptying positions it as a therapeutic linchpin. However, the limited applicability of native GLP-1 stems from its short half-life, primarily due to glomerular filtration and the inactivating effect of dipeptidyl peptidase-IV (DPP-IV). To address this, various structural modification strategies have been developed to extend GLP-1's half-life. Despite the commendable efficacy displayed by current GLP-1 receptor agonists, inherent limitations persist. A paradigm shift emerges with the advent of unimolecular multi-agonists, such as the recently introduced tirzepatide, wherein GLP-1 is ingeniously combined with other gastrointestinal hormones. This novel approach has captured the spotlight within the diabetes and obesity research community. This review summarizes the physiological functions of GLP-1, systematically explores diverse structural modifications, delves into the realm of unimolecular multi-agonists, and provides a nuanced portrayal of the developmental prospects that lie ahead for GLP-1 analogs.

Progress in approved drugs from natural product resources.

Natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impacts on the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs or indirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United States, and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, central nervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

Optimized Transition Metal Phosphides for Direct Seawater Electrolysis: Current Trends.

Seawater electrolysis presents a viable route for sustainable large-scale hydrogen production, yet its practical application is hindered by several technical challenges. These include the sluggish kinetics of hydrogen evolution, poor stability, cation deposition at the cathode, electrode corrosion, and competing chloride oxidation at the anode. To overcome these obstacles, the development of innovative electrocatalysts is crucial. Transition metal phosphides (TMPs) have emerged as promising candidates owing to their superior catalytic performance and tunable structural properties. This review provides a comprehensive analysis of recent progress in the structural engineering of TMPs tailored for efficient seawater electrolysis. We delve into the catalytic mechanisms underpinning hydrogen and oxygen evolution reactions in different pH conditions, along with the detrimental side reactions that impede hydrogen production efficiency. Several methods to prepare TMPs are then introduced. Additionally, detailed discussions on structural modifications and interface engineering tactics are presented, showcasing strategies to enhance the activity and durability of TMP electrocatalysts. By analyzing current research findings, our review aims to inform ongoing research endeavors and foster advancements in seawater electrolysis for practical and ecologically sound hydrogen generation.

Small-molecule agents for treating skin diseases.

Skin diseases are a class of common and frequently occurring diseases that significantly impact daily lives. Currently, the limited effective therapeutic drugs are far from meeting the clinical needs; most drugs typically only provide symptomatic relief rather than a cure. Developing small-molecule drugs with improved efficacy holds paramount importance for treating skin diseases. This review aimed to systematically introduce the pathogenesis of common skin diseases in daily life, list related drugs applied in the clinic, and summarize the clinical research status of candidate drugs and the latest research progress of candidate compounds in the drug discovery stage. Also, it statistically analyzed the number of publications and global attention trends for the involved skin diseases. This review might provide practical information for researchers engaged in dermatological drugs and further increase research attention to this disease area.

The effects of resonance acoustic mixing modulation on the structural and emulsifying properties of pea protein isolate.

The effects of resonant acoustic mixing (RAM) with different treatment times (0, 5, 10, 15, 20 and 30 min) on the structural and emulsifying properties of pea protein isolate (PPI) were investigated for the first time. Increasing the RAM treatment time from 0 to 20 min decreased the α-helix/ß-sheet ratio and particle size of the PPI samples by 37.84 % and 46.44 %, respectively, accompanied by an increase in solubility from 54.79 % to 71.80 % (P < 0.05). Consequently, the emulsifying activity index of PPI (from 10.45 m2/g to 14.2 m2/g) and the physical stability of RAM-PPI emulsions were effectively enhanced, which was confirmed by the small and uniformly distributed oil droplets in the micrographs of the emulsions. However, excessive RAM treatment (30 min) diminished the effectiveness of the aforementioned improvements. Therefore, obviously enhanced solubility and emulsifying properties of PPI can be attained through proper RAM treatment (15-20 min).

Design, synthesis, and biological evaluation of gambogenic acid derivatives: Unraveling their anti-cancer effects by inducing pyroptosis.

Gambogenic acid (GNA), a caged xanthone derived from Garcinia hanburyi, exhibits a wide range of anti-cancer properties. The caged skeleton of GNA serves as the fundamental pharmacophore responsible for its antitumor effects. However, limited exploration has focused on the structural modifications of GNA. This study endeavors to diversify the structure of GNA and enhance its anti-cancer efficacy. Sulfoximines, recognized as pivotal motifs in medicinal chemistry due to their outstanding properties, have featured in several anti-cancer drugs undergoing clinical trials. Accordingly, a series of 33 GNA derivatives combined with sulfoximines were synthesized and evaluated for their anti-cancer effects against MIAPaCa2, MDA-MB-231, and A549 cells in vitro. The activity screening led to the identification of compound 12k, which exhibited the most potent anti-cancer effect. Mechanistic studies revealed that 12k primarily induced pyroptosis in MIAPaCa2 and MDA-MB-231 cells by activating the caspase-3/gasdermin E (GSDME) pathway. These findings suggested that 12k is a promising drug candidate in cancer therapy and highlighted the potential of sulfoximines as a valuable functional group in drug discovery.

Structurally Modified Polysaccharides: Physicochemical Properties, Biological Activities, Structure-Activity Relationship, and Applications.

Polysaccharides are an important class of biomolecules derived from several sources. However, the inherent structure of polysaccharides prevents them from exhibiting favorable physicochemical properties, which restricts their development in agriculture, industry, food, and biomedicine. This paper systematically summarizes the changes in the primary and advanced structures of modified polysaccharides, and focuses on the effects of various modification methods on the hydrophobicity, rheological properties, emulsifying properties, antioxidant activity, hypoglycemic, and hypolipidemic activities of polysaccharides. Then there is a list the applications of modified polysaccharides in treating heavy metal pollutants, purifying water resources, improving beverage stability and bread quality, and precisely delivering the drug. When summarized and reviewed, the information above can shed further light on the relationship between polysaccharide structure and function. Determining the structure-activity relationship provides a scientific basis for the direction of molecular modifications of polysaccharides.

Research progress on the pharmacological mechanism, in vivo metabolism and structural modification of Erianin.

Erianin is an important bibenzyl compound in dendrobium and has a wide spectrum of pharmacological properties. Since Erianin was discovered, abundant results have been achieved in the in vitro synthesis, structural modification, and pharmacological mechanism research. Researchers have developed a series of simple and efficient in vitro synthesis methods to improve the shortcomings of poor water solubility by replacing the chemical structure or coating it in nanomaterials. Erianin has a broad anti-tumor spectrum and significant anti-tumor effects. In addition, Erianin also has pharmacological actions like immune regulation, anti-inflammatory, and anti-angiogenesis. A comprehensive understanding of the synthesis, metabolism, structural modification, and pharmacological action pathways of Erianin is of great value for the utilization of Erianin. Therefore, this review conducts a relatively systematic look back at Erianin from the above four aspects, to give a reference for the evolvement and further appliance of Erianin.

Plant polysaccharides extracted by high pressure: A review on yields, physicochemical, structure properties, and bioactivities.

Polysaccharides are biologically essential macromolecules, widely exist in plants, which are used in food, medicine, bioactives' encapsulation, targeted delivery and other fields. Suitable extraction technology can not only improve the yield, but also regulate the physicochemical, improve the functional property, and is the basis for the research and application of polysaccharide. High pressure (HP) extraction (HPE) induces the breakage of raw material cells and tissues through rapid changes in pressure, increases extraction yield, reduces extraction time, and modifies structure of polysaccharides. However, thus far, literature review on the mechanism of extraction, improved yield and modified structure of HPE polysaccharide is lacking. Therefore, the present work reviews the mechanism of HPE polysaccharide, increasing extraction yield, regulating physicochemical and functional properties, modifying structure and improving activity. This review contributes to a full understanding of the HPE or development of polysaccharide production and modification methods and promotes the application of HP technology in polysaccharide production.