Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a thermosensitive chitosan (CS)–sea cucumber peptide (SCP) hydrogel (CS–SCP gel) loaded with SCP using NaHCO3 as a crosslinker and characterized its properties. Kunming mouse models of anti-intoxication and acute alcohol-induced liver and brain injuries were established. The anti-intoxication and organ-protective effects of the CS–SCP gel were comprehensively evaluated through behavioral observation, liver histopathology, and biochemical assays of serum and liver, kidney, and brain tissues. The CS–SCP gel exhibited a phase transition temperature of 35.7 °C, a water absorption rate of 1015.47%, and a cumulative peptide release of 74.83% within 330 min. In mice, it prolonged the latency to drunkenness; shortened alcohol-induced sleep and sobering time; reduced blood ethanol, transaminase, and lipid levels; upregulated hepatic antioxidant enzymes; downregulated pro-inflammatory cytokines, and alleviated lipid peroxidation. It also enhanced brain antioxidant capacity, suppressed cerebral inflammatory cytokines, and maintained cholinergic neurotransmitter homeostasis. Collectively, with sustained release, CS–SCP gel is expected to prolong the pharmacological action of SCP, enhance therapeutic efficacy, and protect against alcohol-induced liver and brain injury through the regulation of oxidative stress and attenuation of inflammation.
We have developed a visible-light-driven photocatalytic tandem reaction system to achieve the efficient synthesis of 2-sulfenylated pyrrolo[1,2-α]quinoxalines based on a radical addition-cyclization mechanism. Mechanistic studies show that the sulfur radical intermediates generated in the reaction system directly participate in the subsequent formation of C-S bonds. This strategy has opened up an efficient synthetic pathway for the precise synthesis of C2-sulfur-substituted heterocyclic compounds.
Alzheimer’s disease (AD) is a common neurodegenerative disorder with limited effective treatments. Cod skin collagen peptides (CSCPs) have neuroprotective potential for AD but face poor bioavailability—due to gastrointestinal enzyme cleavage and hepatic first-pass metabolism—prompting this study to develop a nanodelivery system to enhance CSCPs’ efficacy. Trimethyl chitosan (TMC)-based CSCP-loaded nanoparticles (CSCPs-NPs) were synthesized via ionic gelation, characterized for physicochemical properties, and tested in a D-galactose-induced AD mouse model (six groups: normal control, model, CSCPs low/high dose, blank NPs, CSCPs-NPs) using behavioral tests, histopathology, immunohistochemistry, and ELISA. CSCPs-NPs had a hydrodynamic diameter of 93.25 ± 21.52 nm, polydispersity index of 0.18 ± 0.13, 61.17% encapsulation efficiency, and sustained 24 h release. In AD mice, CSCPs-NPs significantly improved cognitive function and motor coordination, reduced hippocampal atrophy, preserved neurons, and mitigated oxidative stress, neuroinflammation, and apoptosis (upregulated Bcl-2, downregulated Bax)—effects matching high-dose free CSCPs. This TMC-based nanoformulation enhances CSCPs’ bioavailability and provides a promising strategy for AD intervention.
琼胶广泛应用于食品、保健品、日用化工、医药行业、生物工程等各个领域.随着医药、生物工程等工业的快速发展,对琼胶透明度的要求不断提高.本文在企业生产琼胶粉的基础上,采用单因素实验和正交优化实验的方法,对琼胶进行脱色和除去固体不溶物研究,探索制备高透明度琼胶的最优工艺参数.结果显示,制备高透明度琼胶的最佳条件为:活性炭0.70%、硅藻土1.00%、温度95℃、脱色时间25 min、1.30%琼胶溶液,按此条件制备的琼胶溶液,脱色率达39.73%.本研究结果可为关于琼胶品质提高等方面的研究提供参考依据,促进琼胶在各领域的应用发展.
Background:Photoaging decreases quality of life and increases the risk of skin cancer, underscoring the urgent need to explore natural, high-efficacy, anti-skin photoaging (SP) active substances.Methods:In this study, a gel (CS/CSCPs/β-GP gel) was prepared using chitosan (CS) and sodium β-glycerophosphate (β-GP) through crosslinking with small molecular CSCPs as the carried drug. We evaluated its structural characteristics and properties. The effect of CS/CSCPs/β-GP gel on the degree of ultraviolet (UV)-induced skin aging of mice was investigated through comparative analysis of skin damage, the integrity of collagen tissues and elastic fibers, levels of reactive oxygen species (ROS) and key inflammatory factors (tumor necrosis factor [TNF]-α and interleukin [IL]-1β, IL-6, and IL-10), and tissue expression of matrix metalloproteinase-3 (MMP-3) after repeated UV irradiation in a nude mice SP model.Results:The results showed that CS/CSCPs/β-GP gel was successfully prepared and had the desired characteristics. Compared with CSCPs alone, the CS/CSCPs/β-GP gel more evidently improved typical photoaging characteristics on mouse dorsal skin. It also increased the moisture content, causing the skin to become glossy and elastic. Pathological skin analysis revealed that this peptide-carrying gel can effectively inhibit epidermal thickening, reduce tissue inflammatory infiltration, suppress collagen fiber degradation, increase the collagen content, alleviate structural elastic fiber damage, and significantly inhibit abnormal MMP-3 expression. In addition, biochemical analysis showed that the CS/CSCPs/β-GP gel can effectively inhibit the elevated expressions of ROS and key proinflammatory factors (TNF-α, IL-1β, IL-6) in photoaging skin tissues and promote expression of the anti-inflammatory factor IL-10.Conclusion:SP can cause many clinical skin diseases, such as solar freckle-like nevus, solar keratosis, cutaneous melanoma, and squamous cell carcinoma. CSCPs are a high-efficacy anti-SP natural active substance and CS/CSCPs/β-GP gel can synergistically enhance the CSCPs' anti-SP effect. The mechanism is likely related to the inhibited activation of ROS/nuclear transcription factor-κB signaling and the expression of downstream inflammatory factors.
为促进德育与专业理论知识的实践化,有效且持续提升《生药学》课程整体教学质量,我校《生药学》课程组通过优化组合教学方法,互联互通线上线下、课内课外,打造"理实一体化"的共情育人形式,创设自我教育与朋辈教育相协同的思政育人组合,开展全员参与小组合作探究式学习,构建多元化过程性评价体系,探索形成了基于"理实融通"的共建式教学创新模式.该模式通过促进教学迭代优化,重点突破自主学习激励、理论与实践融通、课程思政、考核评价、课程资源建设等问题,有效解决了教学中存在的痛点问题,让学生、教师、课程得以共同成长和发展.本研究的创新模式符合新医科背景下对新型药学人才的培养要求,以期为其他课程的教学改革与创新提供借鉴.
目的:甘草次酸具有多种药理作用,如抗肿瘤、抗炎和抗病毒等.对甘草次酸进行修饰,制成靶向缓释制剂可以使药物准确到达作用部位,降低对其他组织的伤害.实验制备去唾液酸糖蛋白受体介导的甘草次酸壳聚糖微球,并对所制备的微球进行表征和质量评价.方法:采用乳化交联法制备,并对壳聚糖微球的粒径、Zeta电位、红外光谱图、包封率和载药量、体外释放度及稳定性等方面进行考察.结果:制备的微球粒径为1.106~1.718 μm,Zeta电位为(15.13±1.76)mV,包封率为82.4%,载药量为1.02%,24 h体外释放度为77.09%,稳定性有待提高.结论:去唾液酸糖蛋白受体介导的甘草次酸壳聚糖微球,可为研制靶向肝药物提供一定的理论依据和实践基础.
采用低能乳化法制备了N-乙酰D半乳糖胺修饰头孢克洛-壳聚糖纳米乳,测定了纳米乳的粒径和Zeta 电位,通过比较纳米乳和头孢克洛混悬液的累积释药率、考察释放介质和乳化剂用量对纳米乳累积释药率的影响初步研究了其释药性能.结果表明,纳米乳的粒径在60~250 nm范围内,Zeta 电位为(3.63±0.32)mV;相较于头孢克洛混悬液,纳米乳的释药性能更优,但纳米乳不适合在偏碱性环境(pH≥7.3)中释药;在3~8 g 范围内,随着乳化剂用量的增加,纳米乳的累积释药率逐渐升高,当乳化剂用量为8g时,24 h 累积释药率最高达到72.43%;纳米乳的释药行为符合一级释药模型.
Improving the transdermal absorption of weakly soluble drugs for topical use can help to prevent and treat skin photoaging. Nanocrystals of 18β-glycyrrhetinic acid (i.e., NGAs) prepared by high-pressure homogenization and amphiphilic chitosan (ACS) were used to form ANGA composites by electrostatic adsorption, and the optimal ratio of NGA to ACS was 10:1. Dynamic light scattering analysis and zeta potential analysis were used to evaluate the nanocomposites’ suspension, and the results showed that mean particle size was 318.8 ± 5.4 nm and the zeta potential was 30.88 ± 1.4 mV after autoclaving (121 °C, 30 min). The results of CCK-8 showed that the half-maximal inhibitory concentration (IC50) of ANGAs (71.9 μg/mL) was higher than that of NGAs (51.6 μg/mL), indicating that the cytotoxicity of ANGAs was weaker than that of NGAs at 24 h. After the composite had been prepared as a hydrogel, the vertical diffusion (Franz) cells were used to investigate skin permeability in vitro, and it was shown that the cumulative permeability of the ANGA hydrogel increased from 56.5 ± 1.4% to 75.3 ± 1.8%. The efficacy of the ANGA hydrogel against skin photoaging was studied by constructing a photoaging animal model under ultraviolet (UV) irradiation and staining. The ANGA hydrogel improved the photoaging characteristics of UV-induced mouse skin significantly, improved structural changes (e.g., breakage and clumping of collagen and elastic fibers in the dermis) significantly, and improved skin elasticity, while it inhibited the abnormal expression of matrix metalloproteinase (MMP)-1 and MMP-3 significantly, thereby reducing the damage caused by UV irradiation to the collagen-fiber structure. These results indicated that the NGAs could enhance the local penetration of GA into the skin and significantly improve the photoaging of mouse skin. The ANGA hydrogel could be used to counteract skin photoaging.
Silybin is an antioxidant and anti-lipid peroxidation component. In this experiment, liposomes with different dosages were prepared by thin-film dispersion method, and chitosan was modified to liposomes by dropping method and N-acetyl-D-galactosamine was modified to liposomes by hydration medium.With encapsulation efficiency and drug loading as the main indexes, Fenton method was used to determine the appropriate concentration and clearance rate of liposomes on the ability to scavenge hydroxyl radicals. The results of scavenging hydroxyl radicals showed that when the concentration was 30 μg/mL, the liposomes had the maximum scavenging rate. The highest scavenging rate was 94 % for N-acetyl-D-galactosamine modified silybin liposomes with a dosage of 0.0100 g. The encapsulation efficiency(93.76 %) and drug loading(2.65 %) of chitosan-modified silybin liposomes were the best while the dosage was 0.0080 g. Except for chitosan modified silybin liposomes, the hydroxyl radical scavenging rate of other modified silybin liposomes also increased with the encapsulation efficiency and drug loading. There were significant differences between the samples(P<0.05).
强化高校化学化工类课程教师的实验室安全意识是提升师生实验室安全实践能力和维护实验室安全运行的重要保证.针对化学化工类课程教师实验室安全意识内涵的风险意识、防范意识、遵规意识、责任意识及其相互关系,通过加强教师的实验室安全知识继续教育和实践能力培养、发挥制度的作用、教学相长、激发教师的安全意愿、努力营造良好的建言氛围,为提升实验室安全建设质量和人才培养质量助力.
制药工程专业通过多年的实践,构建了"厚基础、宽口径、重实践、强融合"四位一体的制药工程专业新工科创新应用型人才培养体系.通过整体课程体系的优化,强化融合,重视实践与创新能力培养,实施专业厚基础、宽口径的培养,突出特色和倡导个性发展,知识、能力、素养协调提升.实现具有海洋特色的制药工程专业创新应用型人才高质量培养,达到专业发展与行业需求的目标.
There is an urgent need for wound dressings to treat partial-thickness burns. Hydrogels are a promising material that can maintain hydration to promote necrotic tissue removal. Tilapia peptides (TP) and hydroxyapatite (HA) were incorporated into chitosan system to prepare new types of hydrogels. The hydrogels were cross-linking by tannin (TA), which were developed to promote rapid wound healing in a New Zealand rabbit partial-thickness burn model. Nanohydroxyapatite (NHA) was synthesized by coprecipitation method, which made hydrogels have a highly porous structure comprised of interconnected pores, excellent water absorption and low hemolysis. Besides, the hydrogels showed excellent antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as the cytocompatibility on endothelial cells. Moreover, the hydrogels promoted epithelial and dermal regeneration, reduce the expression of TNF-α and IL-6 and promote the skin regeneration by enhancing expression of collagen, STAT3, and VEGF.
Long-term excessive alcohol intake can easily lead to gastritis, gastric ulcer, and gastric bleeding. In this paper, the gastric acid-responsive hydrogel of CS-NAC/alginate/tilapia collagen peptide (CS-NAC/ALG/TCP) was developed. Its structure and properties were determined. The alcohol-induced gastric mucosal injury models in mice were established to evaluate the protective effects of CS-NAC/ALG/TCP. The results showed that CS-NAC/ALG/TCP was successfully fabricated, and it showed a sustained release of TCP, strong mucoadhesion, and excellent biodegradability in vitro. In the animal experiments, CS-NAC/ALG/TCP improved the oxidative stress status of the gastric mucosa by increasing the levels of SOD, GSH, and CAT in tissues. It also down-regulated the expression of MPO, TNF-α, IL-1β, and IL-6, and increased the production of gastric protective factors such as PGE2 and NO in mouse stomach, thereby reducing the alcohol-induced inflammation and protecting the gastric mucosal injury. Besides, CS-NAC/ALG/TCP can also increase the activities of alcohol metabolism enzymes to improve alcohol metabolism, thereby reducing alcoholic damage. In conclusion, CS-NAC/ALG/TCP is a promising candidate for the treatment of alcohol-induced gastric injury.
There is an urgent need for wound dressings to treat partial-thickness burns. Hydrogels are a promising material that can maintain hydration to promote necrotic tissue removal. Tilapia peptides (TP) and hydroxyapatite (HA) were incorporated into chitosan system to prepare new types of hydrogels. The hydrogels were cross-linking by tannin (TA), which were developed to promote rapid wound healing in a New Zealand rabbit partial-thickness burn model. Nanohydroxyapatite (NHA) was synthesized by coprecipitation method, which made hydrogels have a highly porous structure comprised of interconnected pores, excellent water absorption and low hemolysis. Besides, the hydrogels showed excellent antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as the cytocompatibility on endothelial cells. Moreover, the hydrogels promoted epithelial and dermal regeneration, reduce the expression of TNF-α and IL-6 and promote the skin regeneration by enhancing expression of collagen, STAT3, and VEGF.
Purpose: To systematically study and predict the therapeutic targets and signaling pathways of Hippocampus (HPC) against chronic kidney disease (CKD) using network pharmacology.Methods: By combining database mining, literature searching, screening of disease targets, and network construction, the effects of various components of HPC on several proteins related to CKD were predicted and the active compounds were screened. Genes related to the selected compounds were linked using the SEA database. The correlation between CKD and genes was determined using OMIM, DisGenNet, and GeneCards databases. Pathway-enrichment analyses of overlapping genes were undertaken using online databases.Results: A total of 144 compounds in HPC were identified. Analyses of clusters suggest that the active components of HPC and the target genes against the inflammation caused by CKD were due to 10 compounds and 25 genes. Metascape results showed that these HPC targets are related to CKD inflammation.Conclusion: The active components of HPC and the target genes against CKD inflammation are involved in multiple signaling pathways, such as AGE-RAGE, TLR, TNF, and NF-κB. This work provides scientific evidence to support the clinical use of HPC against CKD.
Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18β-glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18β-glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 β-glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was <5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.
Long-term alcohol intake or drinking large quantities of alcohol at one time can cause organ damage, which in turn can lead to chronic diseases. It is of important clinical and social significance to find effective approaches for the prevention and treatment of alcohol-induced diseases. In this paper, sulfhydryl functionalized chitosan (chitosan-N-acetyl-l-cysteine, CS-NAC) and sodium alginate (SA) were used as the matrix materials to contain tilapia peptide (TP), and a gastric acid-response hydrogel (CS-NAC/SA/TP) was prepared. Taking the ethanol adsorption rate as the response index, based on the results of the single factor test, the preparation process of CS-NAC/SA/TP was optimized through the Box-Behnken design. The swelling and antioxidant properties of CS-NAC/SA/TP were tested in vitro, and the protective effects on alcohol-induced acute liver injury and chronic brain injury were assessed in vivo. Structural characterization showed that CS-NAC/SA/TP was successfully prepared. Under the optimal conditions (SA concentration of 1%, MCS-NAC/MCaCO3 of 1 : 1, MSA/MCS-NAC(CaCO3) of 15 : 1), the prepared CS-NAC/SA/TP had a porous structure, a swelling ratio of 2350%, an ethanol adsorption rate of 56.23% and strong antioxidant capacities in vitro. Animal experiment results demonstrated that CS-NAC/SA/TP effectively reduced liver and brain injuries in mice caused by alcoholism. Summarily, these findings indicate that CS-NAC/SA/TP has potential applications in preventing alcohol-induced liver and brain injuries.
18β-Glycyrrhetinic acid (GA) is often topically applied in clinical treatment of inflammatory skin diseases. However, GA has poor solubility in water, which results in poor skin permeability and low bioavailability. Nanocrystallization of drugs can enhance their permeability and improve bioavailability. We prepared GA nanocrystals (Nano GA) by high-pressure homogenization. These nanocrystals were characterized by photon correlation spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffractometry. The ability of Nano GA to improve dermal permeability was investigated ex vivo using Franz diffusion vertical cells and mouse skin. The topical anti-inflammatory activity of Nano GA was assessed in vivo by a 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced model in mouse ears. The average particle size of a GA nanocrystalline suspension was 288.6 ± 7.3 nm, with a narrow particle-size distribution (polydispersity index ∼0.13 ± 0.10), and the particle size of the lyophilized powder increased (552.0 ± 9.8 nm). After nanocrystallization, the thermal stability and crystallinity decreased but solubility increased significantly. Nano GA showed higher dermal permeability than Coarse GA. Macroscopic and staining-based observations of mouse ears and the levels of proinflammatory factors and myeloperoxidase revealed that the Nano GA hydrogel exhibited better anti-edema ability and more strongly inhibited inflammation development than the Coarse GA hydrogel and indomethacin hydrogel (positive drug). These results suggest that Nano GA could be an efficacious topical therapeutic agent for skin inflammation.
When the aquaculture water environment deteriorates or the temperature rises, shrimp are susceptible to viral or bacterial infections, causing a large number of deaths. This study comprehensively evaluated the effects of the oral administration of a chitosan–gentamicin conjugate (CS-GT) after Litopenaeus vannamei were infected with Vibrio parahaemolyticus, through nonspecific immunity parameter detection, intestinal morphology observation, and the assessment of microbial flora diversification by 16S rRNA gene sequencing. The results showed that the oral administration of CS-GT significantly increased total hemocyte counts and reduced hemocyte apoptosis in shrimp (p < 0.05). The parameters (including superoxide dismutase, glutathione peroxidase, glutathione, lysozyme, acid phosphatase, alkaline phosphatase, and phenoloxidase) were significantly increased (p < 0.05). The integrity of the intestinal epithelial cells and basement membrane were enhanced, which correspondingly alleviated intestinal injury. In terms of the microbiome, the abundances of Vibrio (Gram-negative bacteria and food-borne pathogens) in the water and gut were significantly reduced. The canonical correspondence analysis (CCA) showed that the abundances of Vibrio both in the water and gut were negatively correlated with CS-GT dosage. In conclusion, the oral administration of CS-GT can improve the immunity of shrimp against pathogenic bacteria and significantly reduce the relative abundances of Vibrio in aquaculture water and the gut of Litopenaeus vannamei.