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BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Over the past two decades, numerous researchers have provided important evidence regarding the role of tight junction (TJ) proteins in the occurrence and progression of CRC. The causal relationship between the presence of specific TJ proteins and the development of CRC has also been confirmed. Despite the large number of publications in this field, a bibliometric study to review the current state of research and highlight the research trends and hotspots in this field has not yet been performed. AIM: To analyze research on TJs and CRC, summarize the field's history and current status, and predict future research directions. METHODS: We searched the Science Citation Index Expanded database for all literature on CRC and TJs from 2001-2023. We used bibliometrics to analyze the data of these papers, such as the authors, countries, institutions, and references. Co-authorship, co-citation, and co-occurrence analyses were the main methods of analysis. CiteSpace and VOSviewer were used to visualize the results. RESULTS: A total of 205 studies were ultimately identified. The number of publications on this topic has steadily increased since 2007. China and the United States have made the largest contributions to this field. Anticancer Research was the most prolific journal, publishing 8 articles, while the journal Oncogene had the highest average citation rate (68.33). Professor Dhawan P was the most prolific and cited author in this field. Co-occurrence analysis of keywords revealed that "tight junction protein expression", "colorectal cancer", "intestinal microbiota", and "inflammatory bowel disease" had the highest frequency of occurrence, revealing the research hotspots and trends in this field. CONCLUSION: This bibliometric analysis evaluated the scope and trends of TJ proteins in CRC, providing valuable research perspectives and future directions for studying the connection between the two. It is recommended to focus on emerging research hotspots, such as the correlations among intestinal microbiota, inflammatory bowel disease, TJ protein expression, and CRC.
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Antimony ï¼Sbï¼ is a major pollutant that poses a serious threat to the environment in the mining and processing of nonferrous metals, coexisting with sulfide and oxide of arsenic ï¼Asï¼. Microorganisms play an important role in the migration, transformation, and repair of metals in soil. The ecological effects of bioavailable Sb and As on the microbial community in antimony mining areasï¼mining and smelting areasï¼are still poorly understood. The Wenzel method and high-throughput 16S rDNA amplicon were used to characterize soil pollution characteristics in different functional areas, and the relationship between the bacterial community and bioavailable concentrations have been investigated comprehensively. The results showed thatï¼ Chemical speciation of Sb and As were amorphous, and poorly crystalline hydrous oxides of Fe and Al ï¼F3ï¼ > well-crystallized hydrous oxides of Fe and Al ï¼F4ï¼ > residual phases ï¼F5ï¼ > specifically adsorbed ï¼F2ï¼ > non-specifically adsorbed ï¼F1ï¼. According to the estimation of the potential ecological risk index ï¼RIï¼ and geo-accumulation index ï¼Igeoï¼, the Sb pollution degree wasï¼ smelting area > mining area > contrast area, in which the smelting area showed serious pollution, and the mining area showed moderate to severe pollution. The As pollution degree wasï¼ mining area > smelting area > contrast area, in which the mining area and smelting area showed moderate to severe pollution. High-throughput 16S rDNA amplicon showed that Proteobacteria was the most abundant phylum in mining and smelting areasï¼ Kaistobacter, Pseudomonas, Sphingomonas, and Lysobacter were the most abundant microbial generaï¼ Geobacter and Luteolibacter had a high LDA score in mining areasï¼ and Thiobacillus had a high LDA score in antimony-contaminated areas. Spearman correlation analysis, variation partitioning analysis ï¼VPAï¼, and random forest ï¼RFï¼ analysis showed that Sb, As, bioavailable antimony [Sb ï¼Bioï¼], and bioavailable arsenic [As ï¼Bioï¼]were the main factors affecting the microbial community structure in different functional areas of antimony ore. Redundancy analysis ï¼RDAï¼ indicated that Sb and its bioavailable concentrations showed uniformly negative associations with the relative abundance of bacteria Nitrospirae and showed a significant positive correlation with Thiobacillus ï¼P<0.05ï¼. The in-depth research on the ecological effects of bioavailable Sb and As on the bacterial community provides references and new perspectives for environmental monitoring and management.
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Antimônio , Arsênio , Monitoramento Ambiental , Mineração , Microbiologia do Solo , Poluentes do Solo , China , Poluentes do Solo/análise , Bactérias/classificação , Bactérias/genéticaRESUMO
Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.
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Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Macrófagos , Obesidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/complicações , Obesidade/tratamento farmacológico , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/complicações , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Medicina Tradicional ChinesaRESUMO
To enhance the stability and light resistance of the yellow compounds in citrus pomace, our study successfully isolated and purified five compounds using ultrasonic-assisted extraction and column chromatography. The identified compounds include methyl linoleate, (2-ethyl)hexyl phthalate, 1,3-distearoyl-2-oleoylglycerol, 6,6-ditetradecyl-6,7-dihydroxazepin-2(3H)-one, and n-octadeca-17-enoic acid. The monomers extracted from fresh pomace, compounds 1 and 2, exhibit structural similarities to flavonoids and carotenoids. In contrast, the polymers isolated from fermented pomace, compounds 3, 4, and 5, share structural units with the fresh pomace compounds, indicating the transformation to stable polymeric forms. This suggests that the microbial fermentation process not only enhances the value of citrus pomace, but also provides a promising pathway for the synthesis of natural antioxidant yellow pigments with far-reaching theoretical and practical significance.
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Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a ß-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.
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Amidas , Ácido Aspártico , Lactamas , Peptídeos Cíclicos , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Lactamas/química , Lactamas/síntese química , Amidas/química , Amidas/síntese química , Ácido Aspártico/química , Ácido Aspártico/síntese química , Ácido Aspártico/análogos & derivados , Técnicas de Síntese em Fase Sólida , Estrutura MolecularRESUMO
This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Água , Semântica , PrescriçõesRESUMO
This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrinâ¶microcrystalline cellulose(MCC)â¶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1â¶2â¶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.
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Medicamentos de Ervas Chinesas , Excipientes , Excipientes/química , Medicina Tradicional Chinesa , Água/química , Medicamentos de Ervas Chinesas/químicaRESUMO
In recent years, as people's living standards continue to improve, and the pace of life accelerates dramatically, the demand and quality of traditional Chinese medicine(TCM) services from patients continue to rise. As an essential supplement to the existing forms of TCM application, such as Chinese patent medicine, decoction, and formulated granules, presonalized TCM preparations is facing an increasing market demand. Currently, manual and semi-mechanized production are the primary production ways in presonalized TCM preparations. However, the production process control level is low, and digitalization and informatization need to be improved, which restricts the automated and intelligent development of presonalized TCM preparations. Presonalized TCM preparations faces a significant opportunity and challenge in integrating with intelligent manufacturing through research and development of intelligent equipment and core technology. This paper overviews the connotation and characteristics of intelligent manufacturing and summarizes the application of intelligent manufacturing technologies such as "Internet of things" "big data", and "artificial intelligence" in the TCM industry. Based on the innovative research and development model of "intelligent classification of TCM materials, intelligent decision making of prescription and process, and online control and intelligent production" of presonalized TCM preparations, the research practice and achievements from our research group in the field of intelligent manufacturing of presonalized TCM preparations are introduced. Ultimately, the paper proposes the direction for developing intelligent manufacturing of presonalized TCM preparations, which will provide a reference for the research and application of automation and intelligence of presonalized TCM preparations.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Controle de Qualidade , Tecnologia Farmacêutica , InteligênciaRESUMO
This paper aims to study the correlation between the physicochemical properties of raw materials and intermediates and the molding quality and law of traditional Chinese medicine(TCM) gel plaster by using TCM slices and powder as raw materials. 48 TCM compounds are selected as model prescriptions to prepare gel plasters. The rotational rheometer is used to determine the rheological parameters of the plaster, including storage modulus(G'), loss modulus(Gâ³), yield stress(τ), and creep compliance [J(t)]. The molding quality of the prepared TCM gel plaster is evaluated by subjective and objective measures. Clustering and principal component analysis are conducted to evaluate the physical properties of the plaster. By measuring the rheological properties of the plaster, the molding quality of the TCM gel plaster can be predicted, with an accuracy of 83.72% after seven days of modeling and 88.37% after 30 days of modeling. When the parameters such as G' and Gâ³ of the plaster are large, and the [J(t)] is small, the molding quality of the plaster is better. When the plaster coating point is no less than 3, it is difficult to be coated. In addition, when the proportion of metal ions in the prescription is higher, the 30-day forming quality of the plaster is mainly affected, and the viscosity of the plaster is poor. If the prescription contains many acidic chemical components, the 7-day forming quality of the plaster is mainly affected, with many residuals. The results suggest that the rheological properties of the plaster can be used to predict the molding quality of TCM slice and powder gel plaster. It can provide a reference for the development of TCM gel plaster prescriptions.
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Medicina Tradicional Chinesa , Prescrições , Pós , Viscosidade , ReologiaRESUMO
A method for material classification of traditional Chinese medicines based on the physical properties of powder has been established by our research group. This method involves pre-treatment of traditional Chinese medicine decoction pieces, powder preparation, and determination of physical properties, being cumbersome. In this study, the word segmentation logic of semantic analysis was adopted to establish the thesaurus and local standardized semantic word segmentation database with the macroscopic and microscopic characteristics of 36 model traditional Chinese medicines as the basic data. The physical properties of these medicines have been determined and the classification of these medicines is clear in the cluster analysis. A total of 55 keywords for powdery, fibrous, sugary, oily, and brittle materials were screened by association rules and the set inclusion and exclusion criteria, and the weights of the keywords were calculated. Furthermore, the algorithms of the keyword matching scores and the computation rules of the single or multiple material classification were established for building the intelligent model of semantic analysis for the material classification. The semantic classification results of the other 35 TCMs except Pseudostellariae Radix(multi-material medicine) agreed with the clustering results based on the physical properties of the powder, with an agreement rate of 97.22%. In model validation, the prediction results of semantic classification of traditional Chinese medicines were consistent with the clustering results based on the physical properties of powder, with an agreement rate of 83.33%. The results showed that the method of material classification based on semantic analysis was feasible, which laid a foundation for the development of intelligent decision-making technology for personalized traditional Chinese medicine preparations.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Pós , Semântica , Raízes de PlantasRESUMO
This study aims to optimize the matrix formulation for the hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine(TCM) preparations and verify the applicability of the formulation. The central composite design in JMP Pro 16.1.0 was employed to optimize the dosages of styrene-isoprene-styrene triblock copolymer(SIS), hydrogenated petroleum resin, and lightweight liquid paraffin, with the fine powder of Yipifang as the model drug(drug loading of 10%) and the sensory score and objective evaluation as the comprehensive evaluation indicators. The quality evaluation system of hot-melt pressure-sensitive adhesive plaster of personalized TCM preparations was established. The applicability of the optimized matrix formulation of hot-melt pressure-sensitive adhesive plaster was verified with 16 TCM preparations for external application. Furthermore, the applicability of the matrix formulation was investigated with different drug loadings. The general molding matrix formulation was SISâ¶hydrogenated petroleum resinâ¶lightweight liquid paraffin 3â¶3â¶5. The optimized matrix formulation showed good molding properties and high quality scores for 16 TCM preparations and were suitable for the plastering of finely powdered decoction pieces with a loading capacity of 10% to 30%. The results suggest that the optimized matrix formulation has good applicability and is suitable for TCM preparations. The findings lay a foundation for the application and promotion of the hot-melt pressure-sensitive adhesive plasters of personalized TCM preparations.
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Medicamentos de Ervas Chinesas , Petróleo , Medicina Tradicional Chinesa , Óleo Mineral , PoliestirenosRESUMO
In the process of preparing presonalized concentrated watered pills, the decoction needs to be concentrated by heat and mixed with medicinal slices or powder to prepare a wet mass. However, some of the traditional Chinese medicine(TCM) components are easily decomposed or transformed by heat. In order to optimize the preparation process of presonalized TCM concentrated watered pills and reduce the loss of heat-unstable components in prescriptions, this study uses five compound TCM prescriptions containing heat-unstable components as model prescriptions, namely the Linggui Zhugan Formula, Xiaochengqi Formula, Sanpian Formula, Xiaoer Qixing Formula, and Xiaoyao Formula. Based on the two kinds of preparation process of presonalized concentrated watered pills previously established by our research group, whole extract concentrated watered pills and concentrated watered pills without excipients are prepared, respectively. Characteristic maps are measured and compared with those of the corresponding decoction. The results show that the characteristic maps of the concentrated watered pills without excipients of the five model prescriptions are very close to those of the decoction, and the number of characteristic peaks and peak areas are higher than those of whole extract concentrated watered pills. In addition, the peak area of some peaks is higher than that of the corresponding decoction. Thus, it is recommended to select the preparation process of prescription-based concentrated watered pills without excipients based on the "unification of medicines and excipients" to preserve those heat-unstable components more effectively when the prescription contains a heat-unstable component of TCM. This study provides a basis for the subsequent reasonable development and application of presonalized TCM pills.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Excipientes , Temperatura Alta , PrescriçõesRESUMO
OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.
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Antibacterianos , Compostos Azabicíclicos , Proteínas de Bactérias , Ceftazidima , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Testes de Sensibilidade Microbiana , beta-Lactamases , Animais , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/uso terapêutico , Meropeném/farmacologia , Meropeném/administração & dosagem , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Camundongos , beta-Lactamases/genética , Proteínas de Bactérias/genética , Feminino , Sequenciamento Completo do Genoma , Quimioterapia Combinada , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genéticaRESUMO
Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N-oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N-oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N-oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.
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The Qinghai-Tibet Plateau is one of the areas the richest in salt lakes and Artemia sites. As a result of climate warming and wetting, the areas of salt lakes on the plateau have been increasing, and the salinities have decreased considerably since 1990s. However, the impact of salinity change on the genetic diversity of Artemia is still unknown. Kyêbxang Co is the highest (4620 m above sea level) salt lake currently with commercial harvesting of Artemia resting eggs in the world, and harbors the largest Artemia population on the plateau. Its salinity had dropped from â¼67 ppt in 1998 to â¼39 ppt in 2019. Using 13 microsatellite markers and the mitochondrial cytochrome oxidase submit I (COI) gene, we analyzed the temporal changes of genetic diversity, effective population size and genetic structure of this Artemia population based on samples collected in 1998, 2007 and 2019. Our results revealed a steady decline of genetic diversity and significant genetic differentiation among the sampling years, which may be a consequence of genetic drift and the selection of decreased salinity. A decline of effective population size was also detected, which may be relative to the fluctuation in census population size, skewed sex ratio, and selection of the declined salinity. In 2007 and 2019, the Artemia population showed an excess of heterozygosity and significant deviation from Hardy-Weinberg Equilibrium (p < 0.001), which may be associated with the heterozygote advantage under low salinity. To comprehensively understand the impact of climate warming and wetting on Artemia populations on the plateau, further investigation with broad and intensive sampling are needed.
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Artemia , Lagos , Humanos , Animais , Tibet , Lagos/química , Artemia/genética , Anostraca , Mudança Climática , Salinidade , Altitude , Variação GenéticaRESUMO
Bird-mediated dispersal of resting eggs is the main mechanism for Artemia dispersal among catchments. The bisexual populations of Artemia urmiana species complex, which is here considered to be a collection of Artemia genetically close to the so-called "Western Asian Lineage", are mostly distributed in central and western Asia (i.e., in regions falling into the Central Asian Flyway of migratory birds) and live in diversified habitats. Little is known about the genetic relationships among these populations. Aiming to understand the population genetic characteristics and the roles of migratory birds on the dispersal and gene flow of this Artemia group, we evaluated the genetic diversity, genetic differentiation, and gene flow among 14 populations, with their altitudes ranging from 540 to 4870 m above sea level, using 13 microsatellite markers. Almost all populations exhibited high genetic diversity and heterozygote excess, which may be a consequence of combined effects of dispersal and hybridization. The global genetic differentiation (FST) value was 0.092, the pairwise FST values were 0.003-0.246. Discriminant analysis of principal components identified three genetic clusters, consisting of Urmia Lake (Iran), Zhundong (Xinjiang, China), and 12 Qinghai-Tibet Plateau populations, respectively. The among-population genetic differentiation seems to be a consequence of isolation by distance and adaptation to diversified habitats induced by altitudinal gradient. Historical gene flows are asymmetrical, and show an evolutionary source-sink dynamics, with Jingyu Lake (Xinjiang, China) population being the major source. These results support our hypothesis that in Qinghai-Tibet Plateau and surrounding areas the bird-mediated dispersal of Artemia may be biased towards from north to south and/or from higher altitude to lower altitude.
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Anostraca , Artemia , Animais , Artemia/genética , Fluxo Gênico , Genética Populacional , China , Aves , Variação GenéticaRESUMO
Objective: To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD. Methods: Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice. Results: DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA). Conclusion: DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.
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Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Proteínas Quinases Ativadas por AMP/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Antioxidantes/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Mamíferos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
AIM: To investigate the effect of morroniside (Mor) on lipopolysaccharide (LPS)-treated iris pigment epithelial cells (IPE). METHODS: IPE cells were induced by LPS and treated with Mor. Cell proliferation was detected by cell counting kit (CCK) -8, apoptosis was detected by flow cytometry, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA) kits, and the protein expression of TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 was analyzed by Western blotting. In addition, overexpression of TLR4 and Mor treatment of LPS-stimulated IPE cells were also tested for the above indices. RESULTS: Mor effectively promoted the proliferation and inhibited the apoptosis of LPS-treated IPE cells. In addition, Mor significantly reduced the levels of TNF-α, IL-6, and IL-8 and significantly inhibited the expression of TLR4, p-JAK2, and p-STAT3 in LPS-treated IPE cells. The effect of Mor on LPS-treated IPE cells was markedly attenuated after overexpression of TLR4. CONCLUSION: These findings suggest that Mor may ameliorate LPS-induced inflammatory damage and apoptosis in IPE through inhibition of TLR4/JAK2/STAT3 pathway.
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Dysmenorrhea, classified as primary dysmenorrhea and secondary dysmenorrhea, is a common gynecological symptom that seriously affects female daily life. At present, studies on dysmenorrhea are numerous and complex. To better reflect the trend and innovative progress of dysmenorrhea-related research, this study screened papers on the Web of Science from January 1, 1992, to December 31, 2022. A total of 1012 papers were selected and analyzed for their affiliated countries, institutions, authors, keywords, etc. China is the country with the most academic output, Beijing University of Traditional Chinese Medicine is the most influential institution, and Yang Jie, from Chengdu University of Traditional Chinese Medicine, China, is the scholar with the most papers. We consider that the current research focus is on pathogenesis, treatment, epidemiology, and self-management. With increasing research on functional connectivity between dysmenorrhea and various brain regions, functional connectivity has gradually become the forefront of research. We hope our study can promote the further study of dysmenorrhea.