ABSTRACT
The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2â¢- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.
Subject(s)
Photochemotherapy , Photothermal Therapy , Animals , Photochemotherapy/methods , Mice , Female , Mice, Inbred BALB C , Cell Line, Tumor , Infrared Rays , Nanoparticles/chemistry , Nanoparticles/therapeutic useABSTRACT
OBJECTIVE: This study aimed to determine the postoperative effects of music therapy on negative emotions, pain, and inflammatory and physiological parameters in patients undergoing colonoscopic polypectomy. METHODS: Patients who underwent colonoscopic polypectomy in Funan County People's Hospital between March 2020 and June 2023 were selected as the research subjects. Patients were divided into exposure (underwent music therapy) and control (did not undergo music therapy) groups. Baseline characteristics, Self-rating Anxiety Scale (SAS) and Visual Analog Scale (VAS) scores, physiological parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)], and inflammatory marker levels [neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and erythrocyte sedimentation rate (ESR)] of patients before and after exposure to music were determined. The propensity score matching (PSM) method (1:1) was used to balance the baseline characteristics of the two groups. RESULTS: After PSM, the exposure group comprised 50 cases and the control group comprised 50 cases. The baseline characteristics were not significantly different between the two groups (P > 0.05). The postoperative SAS score of the exposure group was significantly lower than that of the control group (P < 0.05). Meanwhile, the postoperative VAS score of the exposure group was nonsignificantly lower than that of the control group (P > 0.05). Furthermore, the postoperative SBP, DBP, and HR levels of the exposure group were significantly lower than that of the control group (P < 0.05). The postoperative levels of NLR, PLR, and ESR were not significantly different between the exposure and control groups (P > 0.05). CONCLUSION: Music therapy exerts beneficial effects on the postoperative psychological and physiological parameters of patients undergoing colonoscopic polypectomy.
Subject(s)
Music Therapy , Music , Humans , Music Therapy/methods , Retrospective Studies , Anxiety/prevention & control , Anxiety/psychology , Music/psychologyABSTRACT
Introduction: Knee osteoarthritis (KOA) is a type of joint disease causing degenerative changes that are challenging to treat. The improved tug-of-war acupuncture (BHZF) can improve joint pain in KOA. However, the associated mechanism has not been validated. Methods: The KOA rabbit model was established. After the surgery, the improved BHZF was provided as an intervention, and the animals were euthanized after 2 weeks. Histopathological changes in the synovium and cartilage were observed on hematoxylin & eosin staining and Safranin O-Fast Green staining. Synovial fluid and serum samples were collected to assess the presence of cytokines using the enzyme-linked immunosorbent assay. The expression of M1 macrophage (CD86) and M2 macrophage (ARG1) markers in the cartilage and synovium was detected via immunohistochemistry and immunofluorescence assays. Results: The improved BHZF could reduce KOA-related pain and inhibit joint swelling. Further, it significantly maintained the morphology of articular chondrocytes in KOA and reduced the decomposition of the cartilage matrix. Then, it significantly reduced the expression of CD86-positive cells (P < 0.05), and increased the expression of ARG1-positive cells in the cartilage and synovium (P < 0.05). Moreover, it significantly decreased the expression of inflammatory factors interleukin (IL)-1 beta and tumor necrosis factor-alpha in the serum and synovial fluid (P < 0.05), and significantly increased the expression levels of anti-inflammatory cytokines IL-4 and IL-10 (P < 0.05). Conclusions: The improved BHZF can relieve pain and improve cartilage damage by regulating macrophage polarization in KOA.
ABSTRACT
Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.
Subject(s)
Gastrointestinal Microbiome , Mice , Animals , Excipients/pharmacology , RNA, Ribosomal, 16S/genetics , Chromatography, Liquid , Tandem Mass Spectrometry , Metabolome , Weight LossABSTRACT
Quantification of liposoluble micronutrients in large-scale vegetable oil samples is urgently needed, because their health benefits are increasingly emphasized. However, current analytical methods are limited to either labor-intensive preparation processes or time-consuming chromatography separation. In this work, an online oil matrix separation strategy for direct, rapid, and simultaneous determination of squalene, tocopherols, and phytosterols in walnut oil (WO) was developed on the basis of the lipid class separation mode of supercritical fluid chromatography. A single run was completed in 13 min containing 6 min of column cleaning and balancing. Satisfactory limit of detections (0.05-0.20 ng/mL), limit of quantifications (0.15-0.45 ng/mL), recoveries (70.61-101.44%), and matrix effects (78.43-91.62%) were achieved, indicating the reliability of this method. In addition, eight sterol esters were identified in WO, which have not previously been reported. The proposed method was applied to characterize the liposoluble micronutrient profile of WO samples obtained from different walnut cultivars, geographical origins, and processes.
Subject(s)
Chromatography, Supercritical Fluid , Juglans , Phytosterols , Sterols/analysis , Squalene/analysis , Tocopherols/chemistry , Reproducibility of Results , Phytosterols/chemistry , Mass Spectrometry , Plant Oils/chemistryABSTRACT
Jujuboside B (JuB), one of the main active triterpenoid saponins from the traditional Chinese medicine Ziziphus jujuba, possesses a wide range of pharmacological activities. However, it is unknown whether JuB can inhibit tumor angiogenesis, a crucial step in solid tumor growth. In this study, we found that JuB significantly inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells in a dose-dependent manner. JuB also suppressed angiogenesis in chick embryo chorioallantoic membranes and Matrigel plugs. Moreover, through angiogenesis inhibition, JuB delayed the growth of human HCT-15 colorectal cancer xenograft in mice. Western blot assay demonstrated that JuB inhibited the phosphorylation of VEGFR2 and its key downstream protein kinases, such as Akt, FAK, Src, and PLCγ1. In conclusion, the antiangiogenic potency and molecular mechanism of JuB are revealed for the first time, indicating that this triterpene saponin may be further explored as a potential drug candidate or lead compound for antiangiogenic cancer therapy.
ABSTRACT
Ginsenosides are major bioactive compounds found in Panax ginseng that exhibit various pharmaceutical properties. Dammarenediol-II, the nucleus of dammarane-type ginsenosides, is a promising candidate for pharmacologically active triterpenes. Dammarenediol-II synthase (DDS) cyclizes 2,3-oxidosqualene to produce dammarenediol-II. Based on the native terpenoids synthetic pathway, a dammarane-type ginsenosides synthetic pathway was established in Chlamydomonas reinhardtii by introducing P. ginseng PgDDS, CYP450 enzyme (PgCYP716A47), or/and Arabidopsis thaliana NADPH-cytochrome P450 reductase gene (AtCPR), which is responsible for producing dammarane-type ginsenosides. To enhance productivity, strategies such as "gene loading" and "culture optimizing" were employed. Multiple copies of transgene expression cassettes were introduced into the genome to increase the expression of the key rate-limiting enzyme gene, PgDDS, significantly improving the titer of dammarenediol-II to approximately 0.2 mg/L. Following the culture optimization in an opt2 medium supplemented with 1.5 mM methyl jasmonate under a light:dark regimen, the titer of dammarenediol-II increased more than 13-fold to approximately 2.6 mg/L. The C. reinhardtii strains engineered in this study constitute a good platform for the further production of ginsenosides in microalgae.
Subject(s)
Chlamydomonas reinhardtii , Ginsenosides , Panax , Triterpenes , Chlamydomonas reinhardtii/genetics , Chlamydomonas reinhardtii/metabolism , Triterpenes/metabolism , Panax/genetics , DammaranesABSTRACT
The DOHaD theory suggests that adverse environmental factors in early life may lead to the development of metabolic diseases including diabetes and hypertension in adult offspring through epigenetic mechanisms such as DNA methylation. Folic acid (FA) is an important methyl donor in vivo and participates in DNA replication and methylation. The preliminary experimental results of our group demonstrated that lipopolysaccharide (LPS, 50 µg/kg/d) exposure during pregnancy could lead to glucose metabolism disorders in male offspring, but not female offspring; however, the effect of folic acid supplementation on glucose metabolism disorders in male offspring induced by LPS exposure remains unclear. Therefore, in this study, pregnant mice were exposed to LPS on gestational day (GD) 15-17 and were given three doses of FA supplementation (2 mg/kg, 5 mg/kg, or 40 mg/kg) from mating to lactation to explore its effect on glucose metabolism in male offspring and the potential mechanism. This study confirmed that FA supplementation of 5 mg/kg in pregnant mice improved glucose metabolism in LPS-exposed offspring during pregnancy by regulating gene expression.
Subject(s)
Glucose Metabolism Disorders , Prenatal Exposure Delayed Effects , Pregnancy , Female , Humans , Animals , Mice , Male , Lipopolysaccharides/adverse effects , Prenatal Exposure Delayed Effects/chemically induced , Folic Acid/adverse effects , Dietary Supplements , Glucose/metabolismABSTRACT
This study aimed to identify the direct pharmacological targets of Jingfang Granules in treating infectious pneumonia via "target fishing" strategy. Moreover, the molecular mechanism of Jingfang Granules in treating infectious pneumonia was also investigated based on target-related pharmacological signaling pathways. First, the Jingfang Granules extract-bound magnetic nanoparticles were prepared, which were incubated with lipopolysaccharide(LPS)-induced mouse pneumonia tissue lysates. The captured proteins were analyzed by high-resolution mass spectrometry(HRMS), and the target groups with specific binding to the Jingfang Granules extract were screened out. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was used to identify the target protein-associated signaling pathways. On this basis, the LPS-induced mouse model of infectious pneumonia was established. The possible biological functions of target proteins were verified by hematoxylin-eosin(HE) staining and immunohistochemical assay. A total of 186 Jingfang Granules-specific binding proteins were identified from lung tissues. KEGG pathway enrichment analysis showed that the target protein-associated signaling pathways mainly included Salmonella infection, vascular and pulmonary epithelial adherens junction, ribosomal viral replication, viral endocytosis, and fatty acid degradation. The target functions of Jingfang Granules were related to pulmonary inflammation and immunity, pulmonary energy metabolism, pulmonary microcirculation, and viral infection. Based on the in vivo inflammation model, Jingfang Granules significantly improved the alveolar structure of the LPS-induced mouse model of infectious pneumonia and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6). Meanwhile, Jingfang Gra-nules significantly up-regulated the expressions of key proteins of mitochondrial function COX â £ and ATP, microcirculation-related proteins CD31 and Occludin, and proteins associated with viral infection DDX21 and DDX3. These results suggest that Jingfang Gra-nules can inhibit lung inflammation, improve lung energy metabolism and pulmonary microcirculation, resist virus infection, thus playing a protective role in the lung. This study systematically explains the molecular mechanism of Jingfang Granules in the treatment of respiratory inflammation from the perspective of target-signaling pathway-pharmacological efficacy, thereby providing key information for clinical rational use of Jingfang Granules and expanding potential pharmacological application.
Subject(s)
Anti-Infective Agents , Pneumonia , Animals , Mice , Lipopolysaccharides , Inflammation , Biological Assay , Disease Models, Animal , Interleukin-6ABSTRACT
Authentication of walnut oil (WO) is challenging due to the adulteration of high-linoleic acid vegetable oils (HLOs) with similar fatty acid composition. To allow the discrimination of WO adulteration, a rapid, sensitive and stable scanning method based on supercritical fluid chromatography quadrupole time-of-flight mass spectrometry (SFC-QTOF-MS) was established to profile 59 potential triacylglycerol (TAGs) in HLOs samples within 10 min. Limit of quantitation of the proposed method is 0.002 µg mL-1 and the relative standard deviations range from 0.7% to 12.0%. TAGs profiles of WO samples from various varieties, geography origins, ripeness, and processing methods were used to construct orthogonal partial least squares-discriminant analysis (OPLS-DA) and OPLS models that were highly accurate in both qualitative and quantitative prediction at adulteration levels as low as 5% (w/w). This study advances the TAGs analysis to characterize vegetable oils and holds promise as an efficient method for oil authentication.
Subject(s)
Juglans , Plant Oils , Plant Oils/chemistry , Linoleic Acid/analysis , Triglycerides/chemistry , Food Contamination/analysisABSTRACT
Periconceptional folate supplementation is prevalent, raising concerns about possible side effects. The aim of this study was to investigate the associations of folic acid supplementation, dietary folate, serum folate with gestational diabetes mellitus (GDM) risk. In this matched case-control study, 81 pregnant women with GDM (cases) and 81 pregnant women with non-GDM (controls) were identified through age difference (≤3 y) and parity (Both primipara or multipara women) matching, and serum folate levels were measured during the GDM screening (24-28 gestational wk). Folic acid supplementation and dietary folate intake from three months prepregnancy through midpregnancy were assessed using a self-reported questionnaire and food frequency questionnaire. Multivariate binary logistic regression models were used to evaluate the association between folate and GDM. After adjusting for confounding factors, we observed that compared with folic acid supplementation dose ≤400 µg/d, pregnancies without folic acid supplementation and supplemental dose >800 µg/d were associated with GDM risk (adjusted odds ratio=7.25, 95% confidence interval: 1.34-39.36; adjusted odds ratio=4.20, 95% confidence interval: 1.03-17.22), while no significant association with a 400-800 µg/d dose of folic acid supplementation and GDM. Compared with folic acid supplementation dose ≤24 wk, pregnancies without folic acid supplementation were associated with GDM risk (adjusted odds ratio=6.70, 95% confidence interval: 1.22-36.77), while no significant association with folic acid supplementation dose >24 wk and GDM. No significant association of dietary folate and serum folate with GDM was found. No or a higher dose of folic acid supplementation would increase GDM risk and a dose of <800 µg/d is the safe dose.
Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Case-Control Studies , Folic Acid , Logistic Models , Dietary SupplementsABSTRACT
Bacterial fruit blotch (BFB), caused by Acidovorax citrulli, severely damages watermelon, melon, and other cucurbit crops worldwide. Nitrogen, one of the most important limiting elements in the environment, is necessary for the growth and reproduction of bacteria. As a nitrogen-regulating gene, ntrC plays an important role in maintaining bacterial nitrogen utilization and biological nitrogen fixation. However, the role of ntrC has not been determined for A. citrulli. In this study, we constructed a ntrC deletion mutant and a corresponding complementary strain in the background of the A. citrulli wild-type strain, Aac5. Through phenotype assays and qRT-PCR analysis, we investigated the role of ntrC in A. citrulli in nitrogen utilization, stress tolerance, and virulence against watermelon seedlings. Our results showed that the A. citrulli Aac5 ntrC deletion mutant lost the ability to utilize nitrate. The ntrC mutant strain also exhibited significantly decreased virulence, in vitro growth, in vivo colonization ability, swimming motility, and twitching motility. In contrast, it displayed significantly enhanced biofilm formation and tolerance to stress induced by oxygen, high salt, and copper ions. The qRT-PCR results showed that the nitrate utilization gene nasS; the Type III secretion system-related genes hrpE, hrpX, and hrcJ; and the pili-related gene pilA were significantly downregulated in the ntrC deletion mutant. The nitrate utilization gene nasT, and the flagellum-related genes flhD, flhC, fliA, and fliC were significantly upregulated in the ntrC deletion mutant. The expression levels of ntrC gene in the MMX-q and XVM2 media were significantly higher than in the KB medium. These results suggest that the ntrC gene plays a pivotal role in the nitrogen utilization, stress tolerance, and virulence of A. citrulli.
ABSTRACT
Purpose: Kanglaite injection (KLTi), made of Coix seed oil, has been shown to be effective in the treatment of numerous cancers. However, the anticancer mechanism requires further exploration. This study aimed to investigate the underlying anticancer mechanisms of KLTi in triple-negative breast cancer (TNBC) cells. Methods: Public databases were searched for active compounds in KLTi, their potential targets and TNBC-related targets. KLTi's core targets and signaling pathways were determined through compound-target network, protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was carried out to predict the binding activity between active ingredients and key targets. In vitro experiments were conducted to further validate the predictions of network pharmacology. Results: Fourteen active components of KLTi were screened from the database. Fifty-three candidate therapeutic targets were selected, and bioinformatics analysis was performed to identify the top two active compounds and three core targets. GO and KEGG enrichment analyses indicated that KLTi exerts therapeutic effects on TNBC through the cell cycle pathway. Molecular docking results showed that the main compounds of KLTi exhibited good binding activity to key target proteins. Results from in vitro experiments showed that KLTi inhibited proliferation and migration of TNBC cell lines 231 and 468, induced apoptosis, blocked cells in the G2/M phase, downregulated the mRNA expression of seven G2/M phase-related genes cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), and checkpoint kinase 1 (CHEK1), cell division cycle 25A (CDC25A), cell division cycle 25B (CDC25B), maternal embryonic leucine zipper kinase (MELK), and aurora kinase A (AURKA), as well as downregulated CDK1 protein expression and up-regulated protein expression of Phospho-CDK1. Conclusion: By utilizing network pharmacology, molecular docking, and in vitro experiments, KLTi was confirmed to have anti-TNBC effects by arresting cell cycle and inhibiting CDK1 dephosphorylation.
Subject(s)
Drugs, Chinese Herbal , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Molecular Docking Simulation , Network Pharmacology , Cell Cycle , Drugs, Chinese Herbal/pharmacology , Protein Serine-Threonine KinasesABSTRACT
The integration of various two-dimensional (2D) materials on wafers enables a more-than-Moore approach for enriching the functionalities of devices1-3. On the other hand, the additive growth of 2D materials to form heterostructures allows construction of materials with unconventional properties. Both may be achieved by materials transfer, but often suffer from mechanical damage or chemical contamination during the transfer. The direct growth of high-quality 2D materials generally requires high temperatures, hampering the additive growth or monolithic incorporation of different 2D materials. Here we report a general approach of growing crystalline 2D layers and their heterostructures at a temperature below 400 °C. Metal iodide (MI, where M = In, Cd, Cu, Co, Fe, Pb, Sn and Bi) layers are epitaxially grown on mica, MoS2 or WS2 at a low temperature, and the subsequent low-barrier-energy substitution of iodine with chalcogens enables the conversion to at least 17 different 2D crystalline metal chalcogenides. As an example, the 2D In2S3 grown on MoS2 at 280 °C exhibits high photoresponsivity comparable with that of the materials grown by conventional high-temperature vapour deposition (~700-1,000 °C). Multiple 2D materials have also been sequentially grown on the same wafer, showing a promising solution for the monolithic integration of different high-quality 2D materials.
ABSTRACT
Onion center rot is caused by at least four species of genus Pantoea (P. ananatis, P. agglomerans, P. allii, and P. stewartii subsp. indologenes). Critical onion pathogenicity determinants for P. ananatis were recently described, but whether those determinants are common among other onion-pathogenic Pantoea species remains unknown. In this work, we report onion pathogenicity determinants in P. stewartii subsp. indologenes and P. allii. We identified two distinct secondary metabolite biosynthetic gene clusters present separately in different strains of onion-pathogenic P. stewartii subsp. indologenes. One cluster is similar to the previously described HiVir phosphonate biosynthetic cluster identified in P. ananatis and another is a novel putative phosphonate biosynthetic gene cluster, which we named Halophos. The Halophos gene cluster was also identified in P. allii strains. Both clusters are predicted to be phosphonate biosynthetic clusters based on the presence of a characteristic phosphoenolpyruvate phosphomutase (pepM) gene. The deletion of the pepM gene from either HiVir or Halophos clusters in P. stewartii subsp. indologenes caused loss of necrosis on onion leaves and red onion scales and resulted in significantly lower bacterial populations compared with the corresponding wild-type and complemented strains. Seven (halB to halH) of 11 genes (halA to halK) in the Halophos gene cluster are required for onion necrosis phenotypes. The onion nonpathogenic strain PNA15-2 (P. stewartii subsp. indologenes) gained the capacity to cause foliar necrosis on onion via exogenous expression of a minimal seven-gene Halophos cluster (genes halB to halH). Furthermore, cell-free culture filtrates of PNA14-12 expressing the intact Halophos gene cluster caused necrosis on onion leaves consistent with the presence of a secreted toxin. Based on the similarity of proteins to those with experimentally determined functions, we are able to predict most of the steps in Halophos biosynthesis. Together, these observations indicate that production of the toxin phosphonate seems sufficient to account for virulence of a variety of different Pantoea strains, although strains differ in possessing a single but distinct phosphonate biosynthetic cluster. Overall, this is the first report of onion pathogenicity determinants in P. stewartii subsp. indologenes and P. allii. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Subject(s)
Organophosphonates , Pantoea , Pantoea/genetics , Onions/microbiology , Virulence/genetics , Plant Diseases/microbiology , Multigene FamilyABSTRACT
Amomum villosum, serving as an important medicinal material, is complex in the genetic background of germplasm resources. Exploring the genetic diversity and genetic relationship of germplasm resources is conducive to clarifying the germplasm source and genetic background of A. villosum, so as to improve the efficiency of parent selection and variety breeding of A. villosum. Seventy-one pairs of SSR primers were used for PCR amplification of 84 A. villosum samples by polyacrylamide gel electrophoresis. Fifty-four pairs of SSR primers with high polymorphism were screened out for the analysis of genetic diversity. The results showed that 293 alleles were detected from 84 germplasm resources by 54 pairs of SSR primers, with an average of 5.32 alleles for each pair of primers, and a variation range of 3-8, and the primer AVL12 marked the highest number of alleles. The PIC value of each locus varied from 0.068 7 to 0.828 9, with an average of 0.529 9, and the highest was marked by AVL24. The genetic diversity of A. villosum was the highest in Yunnan, followed by Guangxi, and the lowest was found in Guangdong. The population structure analysis and cluster analysis showed that the samples were classified into two groups. In terms of origin, samples from Yunnan and Guangxi had a close genetic relationship, and there was no obvious differentiation of A, villosum resources from different origins. In this study, 54 pairs of SSR markers were used to analyze the genetic diversity and population structure of 84 germplasm resources, which can reflect the genetic relationship between A. villosum samples from different germplasm sources and different populations, thus providing a theoretical basis for the collection, research, and breeding of A. villosum resources.
Subject(s)
Amomum , Microsatellite Repeats , Alleles , Amomum/genetics , China , Genetic Variation , Microsatellite Repeats/genetics , Plant BreedingABSTRACT
The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Photochemotherapy , Staphylococcal Infections , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Lipase/pharmacology , Methylene Blue/pharmacology , Mice , Microbial Sensitivity Tests , Peptides/pharmacology , Peptides/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Silicon Dioxide/pharmacology , Singlet Oxygen , Staphylococcal Infections/drug therapyABSTRACT
Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting "cold" to "hot" tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.
Subject(s)
Ferroptosis , Neoplasms , Quantum Dots , Humans , Mice , Animals , Carbon , CoffeeABSTRACT
OBJECTIVE: The aim of this study was to investigate the relationship between dietary n-6: n-3 poly-unsaturated fatty acids (PUFA) ratio and the risk of developing gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 100 pregnant women were prospectively included for detailed information on dietary intake at 16-18 weeks evaluated using a three-day food record, and subsequent GDM diagnosis at 24-28 weeks. Participants were divided into two groups for analysis: GDM group (n = 22) and control group (n = 78) based on oral glucose tolerance test results performed between 24 and 28 weeks. RESULTS: The average dietary n-6: n-3 PUFA ratio in the control group was 5.63 ± 2.12 and that in the GDM group was 8.35 ± 3.45, within a significant difference (p < .05). A significant difference was associated with a higher dietary n-6: n-3 PUFA ratio and GDM (adjusted odds ratio = 4.29, 95%confidence interval:1.303, 14.124). CONCLUSIONS: Higher dietary n-6: n-3 PUFA ratio was associated with higher odds of GDM. Given the small sample, further studies are required to confirm this hypothesis.
Subject(s)
Diabetes, Gestational , Fatty Acids, Omega-3 , Diet , Female , Glucose Tolerance Test , Humans , Pregnancy , Prospective StudiesABSTRACT
The purpose of this study was to explore the relationship between the characteristics of gut microbiome and the effect of medical nutrition therapy (MNT) on glycemic control in pregnant women with gestational diabetes mellitus (GDM). Seventy-four pregnant women newly diagnosed with GDM received MNT for one-week. The effect of glycemic control was evaluated by fasting and 2-hour postprandial blood glucose; and stool samples of pregnant women were collected to detect the gut microbiome before and after MNT. We used a nested case-control study design, with pregnant women with GDM who did not meet glycemic standards after MNT as the ineffective group and those with an age difference of ≤5 years, matched for pre-pregnancy body mass index (BMI) 1:1, and meeting glycemic control criteria as the effective group. Comparison of the gut microbiome characteristics before MNT showed that the ineffective group was enriched in Desulfovibrio, Aeromonadales, Leuconostocaceae, Weissella, Prevotella, Bacillales_Incertae Sedis XI, Gemella and Bacillales, while the effective group was enriched in Roseburia, Clostridium, Bifidobacterium, Bifidobacteriales, Bifidobacteriaceae, Holdemania and Proteus. After treatment, the effective group was enriched in Bifidobacterium and Actinomycete, while the ineffective group was enriched in Holdemania, Proteus, Carnobacteriaceae and Granulicatella. In conclusion, the decrease in the abundance of characteristic gut microbiome positively correlated with blood glucose may be a factor influencing the poor hypoglycemic effect of MNT in pregnant women with GDM. Abundance of more characteristic gut microbiome negatively correlated with blood glucose could help control blood glucose in pregnant women with GDM.