Tissue Accumulation Research Articles

Influence of Electrical Conductivity on Plant Growth, Nutritional Quality, and Phytochemical Properties of Kale (Brassica napus) and Collard (Brassica oleracea) Grown Using Hydroponics

Kale (Brassica napus) and collard (Brassica oleracea) are two leafy greens in the family Brassicaceae. The leaves are rich sources of numerous health-beneficial compounds and are commonly used either fresh or cooked. This study aimed to optimize the nutrient management of kale and collard in hydroponic production for greater yield and crop quality. ‘Red Russian’ kale and ‘Flash F1’ collard were grown for 4 weeks after transplanting in a double polyethylene-plastic-covered greenhouse using a nutrient film technique (NFT) system with 18 channels. Kale and collard were alternately grown in each channel at four different electrical conductivity (EC) levels (1.2, 1.5, 1.8, and 2.1 mS·cm−1). Fresh and dry yields of kale increased linearly with increasing EC levels, while those of collard did not increase when EC was higher than 1.8 mS·cm−1. Kale leaves had significantly higher P, K, Mn, Zn, Cu, and B than the collard at all EC levels. Additionally, mineral nutrients (except N and Zn) in leaf tissue were highest at EC 1.5 and EC 1.8 in both the kale and collard. However, the changing trend of the total N and NO3- of the leaves showed a linear trend; these levels were highest under EC 2.1, followed by EC 1.8 and EC 1.5. EC levels also affected phytochemical accumulation in leaf tissue. In general, the kale leaves had significantly higher total anthocyanin, vitamin C, phenolic compounds, and glucosinolates but lower total chlorophylls and carotenoids than the collard. In addition, although EC levels affected neither the total chlorophyll or carotenoid content in kale nor glucosinolate content in either kale or collard, other important health-beneficial compounds (especially vitamin C, anthocyanin, and phenolic compounds) in kale and collard leaves reduced with the increasing EC levels. In conclusion, the kale leaf had more nutritional and phytochemical compounds than the collard. An EC level of 1.8 mS·cm−1 was the optimum EC level for the collard, while the kale yielded more at 2.1 mS·cm−1. Further investigations are needed to optimize nitrogen nutrition for hydroponically grown kale.

Production of Polylactide Nanoparticles Loaded With Isoniazid and Vitamin C: A Promising Candidate for the Treatment of Resistant Forms of Tuberculosis

ABSTRACTNowadays, the method of directed transport of drugs is becoming increasingly important in medicine and pharmacology. It allows for increasing the concentration of delivered substances in a certain place and blocking or severely limiting their accumulation in healthy organs and tissues. One of the promising drug carriers used in the development of controlled drug delivery systems is polylactic acid (PLA). We were interested in using biodegradable polymeric nanoparticles (NPs) loaded with isoniazid (INH) and vitamin C (VC) which have sustained action, targeted delivery, high efficacy, and low toxicity. It will help to expand the use of these simple drugs for the rapid treatment of multidrug‐resistant forms of tuberculosis. Thus, in this work, PLA‐INH‐VC NPs were prepared by double emulsion method where several factors affecting particle size were investigated. TGA/DSC and IR spectroscopy studies identified the presence of molecularly dispersed drugs (INH and VC) in polylactide nanoparticles. VC was found to reduce the degradation of the polymer and thus prolonged the release of the drug from the polymer matrix. PLA‐INH‐VC nanoparticles were analyzed for mycobacterial activity and the nanoparticles were found to inhibit the growth of INH‐resistant mycobacteria.

Influence of Qingzhuan Tea Polysaccharides on F- Adsorption: Molecular Structure, Binding Behavior, and In Vitro and In Vivo Digestion and Metabolism.

The high level of fluoride in Qingzhuan tea (QZT) poses a potential health risk to consumers. This study aims to explore the binding behavior of purified Qingzhuan tea polysaccharides (pTPS) and fluoride ions (F-), as well as their regulatory role in the digestion and metabolism of fluoride. The sugar content of pTPS was 94.64 ± 3.01%, with a molecular weight of 7.373 × 104 Da and high homogeneity. The effects of different proportions and environmental conditions on the adsorption of F- by pTPS were investigated. The influence of the complexation of pTPS and F- on the digestion and metabolism of fluoride was explored using an in vitro gastrointestinal digestion model and C57BL/6 mice. The structural alterations of pTPS were observed during simulated gastrointestinal digestion. Furthermore, pTPS were found to reduce serum fluoride levels and inhibit accumulation in major organs and tissues, especially the heart, liver, kidneys, muscles, and femur. This study investigated the binding pattern between fluorine and pTPS and its influence on the digestion and absorption of fluorine, providing a promising potential for pTPS as a bioadsorbent of fluorine to alleviate the toxicity of fluorine in QZT, which laid a theoretical foundation for the safety of consumption of QZT.

BRD4 Degradation Enhanced Glioma Sensitivity to Temozolomide by Regulating Notch1 via Glu-Modified GSH-Responsive Nanoparticles.

Temozolomide (TMZ) serves as the principal chemotherapeutic agent for glioma; nonetheless, its therapeutic efficacy is compromised by the rapid emergence of drug resistance, the inadequate targeting of glioma cells, and significant systemic toxicity. ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Therefore, to surmount TMZ resistance and achieve efficient and specific drug delivery, a dual-targeted glutathione (GSH)-responsive nanoparticle system (T+A@Glu-NP) is designed and synthesized for the co-delivery of ARV-825 and TMZ. As anticipated, T+A@Glu-NPs significantly enhanced penetration of the blood-brain barrier (BBB), facilitated drug uptake by glioma cells, and exhibited efficient accumulation in brain tissue. Additionally, T+A@Glu-NPs exhibited augmented efficacy against glioma both in vitro and in vivo through the induction of apoptosis, inhibition of proliferation, and cell cycle arrest. Furthermore, mechanistic exploration revealed that T+A@Glu-NPs degraded the BRD4 protein, leading to the downregulation of Notch1 gene transcription and the inhibition of the Notch1 signaling pathway, thereby augmenting the therapeutic efficacy of glioma chemotherapy. Taken together, the findings suggest that T+A@Glu-NPs represents a novel and promising therapeutic strategy for glioma chemotherapy.

Efficacy of soil drench and foliar application of iron nanoparticles on the growth and physiology of Solanum lycopersicum L. exposed to cadmium stress.

Cadmium (Cd) can harm the yield and quality of vegetables, threatening food safety. Essential microelements such as iron are crucial for plant growth and can help alleviate heavy metal stress. Recently, nanoparticles have been studied as eco-friendly solutions for mitigating heavy metal stress in plants. In the present study, iron nanoparticles (FeNPs) at 0, 100, and 300mg/L were applied as soil drenches and foliar sprays to tomato plants under cadmium stress. A comparison was made between the application methods of FeNPs by evaluating the growth parameters of tomato plants, including shoot length (SL), root length (RL), number of branches (NB), number of leaves per plant (NL), and leaf area (LA), as well as by assessing biochemical and antioxidant enzyme parameters. In the Cd stress treatment, the protein content decreased by 24.71%, and the phenolic and flavonoid content of the tomato plants also decreased due to cadmium stress, with levels decreasing from 16.07 to 6.9µg and from 0.36 to 0.16µg, respectively. Compared with the soil drench, 100mg/L FeNPs significantly improved the parameters of Cd-stressed plants when used as a foliar spray, leading to increases in shoot length, root length, fruit weight, number of fruits, number of leaves, and number of branches by 42%, 66%, 24%, 66%, 173%, and 45%, respectively. Tomato plants treated with this spray presented increased carotenoid and lycopene contents. FeNP foliar spray also reduced Cd accumulation in plant tissues. This technique shows promise in alleviating Cd stress in vulnerable vegetable plants such as tomatoes.

Evaluation of Maternal Factors Affecting Postpartum Insulin Resistance Markers in Mothers with Gestational Diabetes—A Case–Control Study

Background: Gestational diabetes mellitus (GDM) is defined by an insufficient insulin response to counteract the insulin resistance (IR) that arises from the physiological adaptations associated with pregnancy. However, the pathophysiology of IR is complex and unclear, as it encompasses elements such as epigenetics, environmental factors, modifiable lifestyle factors, and psychosocial factors. Aim: The objective of this study was to evaluate the influence of GDM and other maternal factors on IR markers in comparison to mothers with normal glucose tolerance during pregnancy in the first week postpartum. Material and Methods: The study population comprised 70 participants, including mothers with gestational diabetes who were treated with a diet and physical activity (GDM G1), with insulin (GDM G2), and a control group of healthy mothers without gestational diabetes (non-GDM). A series of statistical techniques were employed to facilitate the comparison of data between the study groups, with the objective of identifying potential associations with maternal factors. A taxonomic analysis was conducted using the following factors: classification by study group, a history of hypothyroidism in the maternal medical interview, and maternal gestational weight gain, which were identified as the best-fitting predictors. Results: The analysis resulted in the identification of four clusters of patients. Comparison of the insulin resistance markers between mothers assigned to the abovementioned clusters showed differences in the incidence of excessive weight loss and in the results of glucose screening tests during pregnancy. Also, differences concerning fasting glucose levels in the first and second/third trimesters of pregnancy and glucose levels at 1 h post-OGTT were found. For the clusters, the results of the HOMA-IR and the QUICKI did not show any differences in the first week after delivery (p > 0.05). HbA1c results varied significantly. Conclusions: Degree of glucose metabolism disorders, hypothyroidism, and weight gain in pregnancy influence maternal insulin resistance markers in the first week postpartum. Additionally, gestational weight fluctuation has a significant influence on the outcome of pregnancy, particularly with regard to fetal growth and, consequently, the infant’s birth weight and adipose tissue accumulation.

Abstract 4122389: Accumulation of Epicardial Adipose Tissue as a Marker of Diastolic Dysfunction in Patients With Preserved Left Ventricular Ejection Fraction Undergoing Coronary Computed Tomography Angiograph

Background: Left ventricular diastolic dysfunction (LVDD) plays a major role in the pathophysiology of progression to heart failure with preserved left ventricular (LV) ejection fraction (EF). Although epicardial adipose tissue (EAT) is attracting attention for the underlying pathophysiology, whether increased EAT and coronary plaque burden are associated with LVDD is unclear in patients with chronic coronary artery disease (CAD) and preserved LVEF. Aims: To investigate the association between LVDD and EAT accumulation in chronic CAD patients with preserved LVEF. Methods: We included three hundred fourteen chronic CAD and preserved LVEF patients without history of heart failure (mean age: 66±13 years; 48% female). Thoracic tissue doppler echocardiography (TTDE) analysis included LVDD parameters, including left atrial volume index (LAVI), e’, E/e’ and tricuspid regurgitation (TR) velocity. LVDD was defined according to the American Society of Echocardiography guidelines. Coronary computed tomographic angiography (CCTA) analysis included EAT volume index (EAVi), coronary artery calcium score (CACS), and coronary plaque volume (%PV). Patients were divided into three groups according to EAVi: Group A as normal (<68.1 ml/m 2 , n=127), group B as low (68.1-89.4 ml/m 2 , n=95), and group C as high EATVi (>89.4 ml/m 2 , n=92). Multivariable logistic regression analysis was performed to investigate the association between the clinical parameters, TTDE and CCTA findings, and the presence of LVDD. Results: Compared with Group A, group C was older and more frequently suffered from renal dysfunction. Among the three groups, we observed significant differences in LV mass index, e’, E/e’, and CACS. The EAVi correlated with each LVDD diagnostic component, including e’, E/e’, left atrial volume index (all p<0.05), except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; 95% CI, 1.06-1.20; p<0.001] and EAVi (OR, 1.03; 95%CI, 1.01-1.04; p<0.05) were independently associated with LVDD, even after adjusting for LV mass index (OR, 1.1; p < 0.05). There was no independent association of CACS or %PV with LVDD (Table). Conclusion: This study demonstrates that accumulation of EAT and LV mass index but not plaque volume were independent predictors of LVDD in chronic CAD patients with preserved LVEF. Further study is needed to investigate whether EAT predicts the development to heart failure in this population.

Biochar co-compost increases the productivity of Brassica napus by improving antioxidant activities and soil health and reducing lead uptake

Lead (Pb) is a serious toxic metal without any beneficial role in the biological system. Biochar (BC) has emerged as an excellent soil amendment to mitigate Pb toxicity. The impact of BC co-compost (BCC) in mitigating the toxic impacts of Pb has not been studied yet. Therefore, this study aimed to evaluate the potential of BC and BCC in improving the growth, physiological, and biochemical traits of Brassica napus and soil properties and reducing health risks (HR). The study was comprised of different Pb concentrations (control and 100 mg kg-1) and organic amendments (control, BC, compost, and BCC). The results indicated that Pb stress reduced the growth, photosynthetic pigments, seed yield, and oil contents by increasing hydrogen peroxide (H2O2) production and Pb uptake and accumulation in plant tissues and decreasing photosynthetic pigment and nutrient availability. The application of BCC alleviated the adverse impacts of Pb and improved seed production (40.24%) and oil yield (11.06%) by increasing chlorophyll a (43.18%) and chlorophyll b (25.58%) synthesis, relative water content (23.89%), total soluble protein (TSP: 23.14%), free amino acids (FAA: 26.47%), proline (30.98%), APX (40.90%), CAT (32.79%), POD (24.93%), and SOD (33.30%) activity. Biochar co-compost-mediated increase in seed and oil yield was also linked with a reduced accumulation of Pb in plant parts and soil Pb availability and improved the soil-available phosphorus, potassium, total nitrogen, soil organic carbon (SOC), and microbial biomass carbon (MBC). Furthermore, BCC also reduced the bioaccumulation concentration, daily metal intake, hazard index, and target hazard quotient. In conclusion, application of BCC can increase the growth, yield, and oil contents of Brassica napus by improving the physiological and biochemical traits and soil properties and reducing the Pb uptake.

Abstract 4122249: Deletion of macrophage dynamin-related protein 1 exacerbates left ventricular remodeling after myocardial infarction by impairing mitochondrial quality maintenance machinery

Background: Macrophage-mediated inflammation plays an important role in the healing process after myocardial infarction (MI). We have previously reported in macrophages that inhibition of dynamin-related protein 1 (Drp1), which induces mitochondrial fission, restrains skewing toward inflammatory phenotype. It is, however, obscure whether macrophage Drp1 promotes left ventricular (LV) remodeling after MI. Aims: The aim of this study is to elucidate the role of macrophage Drp1 in the mechanisms of LV remodeling after MI. Methods: C57Bl/6J mice specifically deficient Drp1 in Lysozyme-M + macrophages (Drp1KO) were created by Cre/loxP technology and underwent ligation of the left anterior descending coronary artery at 8 to 12 weeks of age. Results: Deletion of macrophage Drp1 decreased LV ejection fraction (38±14 vs. 23±9% at day 28. N=9, p<0.05) and increased LV diameter (LVDd/Ds 5.7±0.4/4.8±0.3 vs. 4.6±0.2/3.7±0.3mm at day 28, N=9, p<0.05) (Figure). Survival rates until 28 days after MI were significantly lower in Drp1KO mice (25 vs. 64%. N=24 and 33, p<0.05). Deletion of Drp1 led to sustained macrophage accumulation and fibrosis of infarcted tissues. TEM revealed that mitophagosomes are decreased in Drp1-deficient macrophages in infarcted hearts. In ex vivo cultured macrophages, siRNA-mediated knockdown of Drp1 impaired mitochondrial fission and LC3-dependent mitophagy. In these macrophages, inhibition of Drp1 by Mdivi-1 for 96 hr, but not for 24 hr, induced mitochondrial DNA (mtDNA) leakage to the cytosol accompanied by increased expression of inflammatory cytokines. Hypoxia and starvation, in addition to Mdivi-1, induced leakage of mtDNA and expression of inflammatory cytokines at 24 hr. These results suggest that impairment of mitochondrial quality maintenance machinery causes leakage of mtDNA that induces inflammation. Conclusions: Macrophage Drp1 protects the heart from sustained inflammation and adverse cardiac remodeling after MI. Drp1-LC3-mediated mitophagy could be a mechanism that maintains mitochondrial quality and prevents excessive inflammation after MI.

DDEL-13. ENHANCING THE EFFICACY OF THE BBB-PENETRANT PEPTIDE-DRUG CONJUGATE PT(IV)-M13 WITH THE KINASE INHIBITOR BIA TO IMPROVE INTRA-TUMORAL DELIVERY AND INHIBIT DNA REPAIR

Abstract The blood-brain and blood-tumor barriers (BBB and BTB) constitute major obstacles to effective GBM therapy. These barriers impede the penetration of the great majority of pharmacological agents into brain tumors. This study introduces a dual-modality approach aimed at enhancing drug delivery to GBM through manipulating BTB permeability and facilitating targeted drug delivery through a novel BBB penetrant drug conjugate. First, we investigated the effects of the broad specificity kinase inhibitor 6-bromo-indirubin-3’-acetoxime (BIA), a derivative of the natural medicinal indirubin, on BTB integrity. These studies revealed that BIA diminishes trans-endothelial electrical resistance and reduces the expression of VE-cadherin in human cerebral microvascular endothelial cells (hCMEC/D3), indicating a loosening of tight junctions. This effect was also observed in mouse GBM models, suggesting a BIA-induced increase in BTB permeability, enhancing the intra-tumoral accumulation and efficacy of non-brain-penetrant therapeutic agents in murine GBM models. Secondly, we have developed Pt(IV)-M13, a perfluoroaryl stapled variant of the cell-penetrating peptide TP10 conjugated to Pt(IV), a prodrug form of cisplatin. This conjugate demonstrates an ability to penetrate the BBB, enhancing drug delivery while limiting exposure to healthy brain tissue, Pt(IV)-M13 exhibits a promising cytotoxic effect on GBM cells, sparing non-tumorous cells, and increases the survival of GBM tumor-bearing mice significantly compared to controls. Our data includes quantitative analysis of platinum accumulation in tumor tissues versus non-targeted regions, highlighting the specificity and potential of this approach. Furthermore, we have found that BIA synergizes with Pt(IV)-M13 in vitro, via inhibition of DNA repair, and are currently investigating the safety and efficacy of administering BIA in conjunction with Pt(IV)-M13 in vivo. This novel strategy holds potential to significantly impact the clinical management of GBM, emphasizing the importance of targeting the BTB in future therapeutic strategies.

EXTH-64. MECHANISMS OF MITOCHONDRIAL COMPLEX-I SENSITIVITY IN GBM

Abstract The biguanide metformin that is widely used for the management of Type 2 diabetes is being evaluated as an anti-neoplastic agent in cancer trials including GBM (NCT02780024, NCT03243851). The mechanisms of action of metformin as an anti-neoplastic agent is still being investigated, but recent studies have unequivocally demonstrated that its therapeutic effects in tumor cell growth and signaling are dependent on inhibition of mitochondrial complex I. Based on the success of metformin in combination therapy in some cancers, new generation of mitochondrial complex I inhibitors (MCI-i) such as IM156, IACS-010759, are currently under investigation. Diffusion of metformin across the plasma membrane occurs slowly. Its entry is facilitated by two transporters OCT1 and OCT2 that are not well expressed outside the liver and kidney. This presents a problem due to its lack of accumulation in other tissues at therapeutic concentrations. Therefore, identification of tumor subtypes that respond better to lower concentrations of metformin may be leveraged for targeted metformin therapy. Metformin GBM trials may be unsatisfactory since there are no molecular markers to distinguish metformin responders from non-responders. Identification of molecular markers may greatly improve metformin and other MCI-i-based therapy in GBM. By examining TCGA data and experimental analysis, we have identified that PDHA, that catalyzes pyruvate to acetyl Co-A, is a predictive molecular marker for MCI-i sensitivity in GBM and potentially beyond GBM. PDHA expression varies widely in patient tumors, potentially due to differential methylation. We are performing joint pathway analysis by examining differentially expressed genes and stable isotope tracing studies to determine distinct metabolic signatures in the two subsets of GBM. We are also performing Classification And Regression Tree (CART) analysis on a cohort of sixty primary GBM lines and tissues to predict if PDHA expression provides a binary outcome for MCI-i sensitivity.

Assessing the effects of cadmium on antioxidant enzymes and histological structures in rainbow trout liver and kidney

Cadmium contamination in aquatic environments poses severe risks to aquatic organisms, particularly fish, where cadmium accumulation in tissues can lead to compromised organ functionality and reproductive issues. The present study aimed to assess the effects of cadmium (Cd) exposure on key biomarkers of oxidative stress, DNA damage, apoptosis, and enzyme activity in the liver and kidney tissues of rainbow trout (Oncorhynchus mykiss). Specifically, the study measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, caspase-3 activation, acetylcholinesterase (AChE) activity, and oxidative stress indicators (ONOO−, MDA, GSH, SOD, and CAT) following exposure to three Cd concentrations (1, 3, and 5 mg/L) over three time points (24, 48, and 96 h). Tissue samples were collected post-exposure, and the analysis revealed a significant decrease in MDA levels in both tissues. GSH concentrations declined with prolonged exposure, while SOD activity increased, indicating a response to oxidative stress, contrasted by a reduction in CAT activity. An initial increase in ONOO− levels was observed at 24 h, followed by a subsequent decrease at the 48 and 96 h marks. These results suggest that cadmium induces oxidative stress in the liver and kidney tissues of fish. Cadmium exposure also significantly elevated 8-OHdG levels, signaling DNA damage, and increased caspase-3 activity, indicative of apoptosis, across all doses and time points (p < 0.05). The histological examination of liver and kidney showed tissue injury. Additionally, a negative correlation between AChE activity and exposure duration was noted, with prolonged exposure resulting in substantial AChE inhibition. Given the role of AChE in behavior regulation, these findings underscore the importance of exploring time-dependent, tissue-specific changes in AChE activity to further elucidate the mechanisms underlying cadmium-induced behavioral abnormalities.

Daily GDF15 treatment has sex-specific effects on body weight and food intake and does not enhance the effects of voluntary physical activity in mice.

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine that suppresses food intake and causes weight loss. GDF15 also reduces voluntary physical activity and, thus, it is not clear whether combining GDF15 with exercise will be beneficial or if reductions in food intake would be offset by decreases in physical activity. We investigated how GDF15 treatment combined with voluntary wheel running (VWR) would impact weight gain, food intake, adiposity and indices of metabolic health in mice. High-fat fed male and female mice underwent daily GDF15 treatments and were given access to voluntary running wheels, or not, for 11days. In both sexes, VWR prevented weight gain. In males, GDF15 reduced food intake, as well as attenuated weight gain and the accumulation of adipose tissue, with no additional effect of VWR. In female mice, GDF15 did not impact body weight gain or body composition. GDF15 acutely reduced food intake in female mice but this was followed by a period of rebound hyperphagia and consequently GDF15 did not reduce total food intake in female mice. GDF15 treatment reduced wheel running distance in both sexes. There were main effects of VWR to improve glucose tolerance in female but not male mice. These findings show that GDF15has sex-specific effects on food intake and consequently weight gain and adiposity. There is no added benefit of combining GDF15 and voluntary physical activity for weight loss. Adaptive responses to acute caloric restriction induced by GDF15might limit its effectiveness as a weight loss tool in females. KEY POINTS: GDF15 is a stress-induced signalling factor that reduces food intake and voluntary physical activity. It is not known whether combining GDF15 treatment with voluntary wheel running would impart beneficial combined effects in attenuating weight gain and the accumulation of adipose tissue. In the present study, we demonstrate that GDF15 reduces food intake and prevents weight gain in male but not female mice consuming a high-fat diet and also that combining GDF15 with voluntary wheel running (VWR) does not lead to a greater dampening of weight gain. In female mice, GDF15 acutely reduced food intake, but this was followed by a period of rebound hyperphagia resulting in no differences in total food intake. In both sexes, VWR was equivalent, or superior to GDF15 in preventing weight gain.

Genome-wide identification and functional analysis of CYP450 genes in eggplant (Solanum melongena L.) with a focus on anthocyanin accumlation

BackgroundIn plants, Cytochrome P450 (CYP450) constitutes the largest family of metabolic enzymes and plays a crucial role in various physiological processes, including plant growth and development. Eggplants are well-known for their peel’s high concentration of anthocyanin compounds that provide significant health benefits to humans. The accumulation of anthocyanins in eggplant peels is an important process during growth and development. Therefore, it is essential to identify the CYP450 genes in eggplant (SmCYPs) and analyze their expression profiles during the period of anthocyanin accumulation in the peel.ResultsA total of 180 SmCYPs were identified in the eggplant genome and classified into eight subfamilies based on phylogenetic analysis. These SmCYPs exhibited highly conserved gene structure (exon/intron) and protein motifs, especially within their respective subgroup. Sixteen pairs of genes with collinearity were identified through gene duplication analysis. Promoter cis-acting element analysis revealed that SmCYPs are involved in various responses, including growth and development, stress responsiveness, and light responsiveness. Transcriptome data analysis revealed that all SmCYPs were expressed in various eggplant tissues, such as roots, stems, leaves, flowers, and fruits; with diverse expression patterns among members. The expression patterns of SmCYPs in eggplant peel also exhibited diversity during different stages of anthocyanin accumulation. qRT-PCR analysis demonstrated similar expression patterns for 15 selected SmCYPs as observed in the transcriptome data. Metabolomics analysis further suggested that SmCYPs are involved in the biosynthesis of secondary metabolites and metabolic pathways related to flavonoid and flavone/flavonol biosynthesis. Notably, three specific SmCYPs (SmCYP73A1/75A/98A1) play a significant role in flavonoid biosynthesis, particularly in anthocyanin synthesis in eggplant.ConclusionGenome-wide identification, phylogenetic analysis, expression profile analysis, and exploration of metabolic pathways related to SmCYPs provide valuable insights into the roles of these genes in anthocyanin accumulation in various tissues and organs, including eggplant peel. The findings from this study lay a foundation for the functional analysis of SmCYPs involvement in anthocyanin accumulation in eggplant peel, providing a molecular basis for breeders to cultivate novel varieties of eggplants with high levels of anthocyanin content.

Combination CXCR4 and PD1 blockade enhances intratumoral dendritic cell activation and immune responses against hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DCs) in liver malignancies. Here, we tested combination blockade of programmed death receptor 1 (PD1) and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors. Using orthotopic grafted and autochthonous HCC models with underlying liver damage, we evaluated treatment feasibility and efficacy. In addition, we examined the effects of treatment using immunofluorescence, flow cytometric analysis of DCs in vivo and in vitro, and RNA-sequencing. Combination anti-CXCR4 and anti-PD1therapy was safe and significantly inhibited tumor growth and prolonged survival in all murine preclinical models of HCC tested. The combination treatment successfully reprogrammed antigen-presenting cells, revealing the potential role of conventional type 1 DCs (cDC1s) in the HCC microenvironment. Moreover, DC reprogramming enhanced anticancer immunity by facilitating CD8+ T-cell accumulation and activation in the HCC tissue. The effectiveness of anti-CXCR4/PD1 therapy was compromised entirely in Batf3-KO mice deficient in cDC1s. Thus, combined CXCR4/PD1 blockade can reprogram intra-tumoral cDC1s and holds the potential to potentiate antitumor immune response against HCC.

Stilbene production as part of drought adaptation mechanisms in cultivated grapevine (Vitis vinifera L.) roots modulates antioxidant status.

Stilbenes, naturally occurring polyphenolic secondary metabolites, play a pivotal role in adaptation of various plant species to biotic and abiotic factors. Recently, increased attention has been directed toward their potential to enhance plant stress tolerance. We evaluated drought tolerance of three grapevine varieties grown with different levels of water deficit. Throughout, we studied physiological mechanisms associated with drought stress tolerance, particularly stilbene accumulation in root tissues, using HPLC. Additionally, we explored the possible relationship between antioxidant potential and stilbene accumulation in response to water deficit. The results underscore the detrimental impact of water deficit on grapevine growth, water status, and membrane stability index, while revealing varying tolerance among the studied genotypes. Notably, Syrah variety had superior drought tolerance, compared to Razegui and Muscat d'Italie grapes. Under severe water deficit, Syrah exhibited a substantial increase in levels of stilbenic compounds, such as t-resveratrol, t-piceatannol, t-ɛ-viniferin, and t-piceid, in root tissues compared to other genotypes. This increase was positively correlated with total antioxidant activity (TAA), emphasizing the active role of resveratrol and its derivatives in total antioxidant potential. This demonstratres the potential involvement of resveratrol and its derivatives in enhancing antioxidant status of the drought-tolerant Syrah grape variety. Our findings suggest that these stilbenes may function as valuable markers in grapevine breeding programs, offering novel insights for the sustainable cultivation of grapevines in water-limited environments.

Angiotensin-Converting Enzyme-Dependent Intrarenal Angiotensin II Contributes to CTP: Phosphoethanolamine Cytidylyltransferase Downregulation, Mitochondrial Membranous Disruption, and Reactive Oxygen Species Overgeneration in Diabetic Tubulopathy.

Aims: The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. Results: Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. Innovation and Conclusion: This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. Antioxid. Redox Signal. 00, 000-000.

Euglena Attenuates High-Fat-Diet-Induced Obesity and Especially Glucose Intolerance.

Background: Obesity, a global disease, can lead to different chronic diseases and a series of social health problems. Lifestyle changes, especially dietary changes, are the most effective way to treat obesity. Euglena, a novel food, has attracted much attention. Previous studies have shown that Euglena is an important modulator of the host immune response. In this study, the effects of Euglena as a nutritional intervention in high-fat-diet-induced obese C57BL/6J mice were investigated regarding adipose tissue accumulation and lipid and glucose metabolism by gavage at the dose of 100 mg/kg bodyweight for 9 weeks. This study is one of the few to investigate, in detail, the preventive effects of dietary Euglena on obesity. Methods: Five-week-old male C57BL/6J mice were fed with a high-fat diet (HFD) to induce obesity. An obesity model was created by feeding the high-fat diet for a period of 10 weeks. Obese mice were randomized into 2 groups with the same mean body weight, and no significant differences were observed between the groups: (1) the mice in the HEG group were maintained on a high-fat diet and daily gavaged with Euglena (100 mg/kg body weight) dissolved in saline (n = 7); and (2) the mice in the HFD group were maintained on a high-fat diet and daily gavaged with saline with the same volume (n = 7). The experiment finished after a nine-week period. Results: The results showed that Euglena could reduce the accumulation of white body fat, including subcutaneous fat and visceral fat, and mainly targeted subcutaneous fat. Euglena also reduced adipocyte particle size expansion, promoted lipolysis in adipose (adipose triglyceride lipase and hormone-sensitive triglyceride lipase) and liver tissue (reduced non-esterified fatty acid content), and improved obesity-induced ectopic fat deposition and glucose tolerance. Conclusions: Our findings suggest that Euglena, as a nutritional intervention in HFDs, efficiently reduces body weight and white adipose tissue deposition. The mechanism of Euglena is mainly though enhancing lipolysis. It is worth noting that Euglena β-glucan recovers the hyperglycemia and accumulation of ectopic fat within the liver induced by HFD. Our study is one of the few studies to report in detail the preventive effects of dietary Euglena on obesity in vivo. This study revealed that Euglena also has an important ameliorative effect on obesity and metabolic disorders, which laid a theoretical foundation for its future application in functional foods.

Photodynamic therapy – modern views and innovations in dentistry

Photodynamic therapy (PDT) consists of three elements: a photosensitizer, light and oxygen. The photosensitizer has the property of selective accumulation in target tissues without harming healthy cells. This innovative therapeutic method has already been successfully adapted in many areas of medicine, such as dermatology, gynecology, urology and oncology. PDT is also beginning to be introduced in dentistry. The antibacterial and fungicidal properties of the photosensitizer are used to achieve better results in the medical and surgical treatment of patients. Objective. To analyze current scientifi data on the application of photodynamic therapy (PDT) in various fi of dentistry, evaluate its effectiveness, and assess prospects for development. Materials and methods. A review of recent scientifi literature was conducted, including original studies, systematic reviews, and meta-analyses focused on PDT application in dentistry. Data on mechanisms of action, clinical efficacy, and new developments in PDT were analyzed. Results. High effi of PDT was established in the treatment of periodontal diseases, peri-implantitis, endodontic infections, and oral oncological diseases. Advantages of combined application of PDT with other treatment methods were noted. Promising directions for PDT development were identifi including the creation of new photosensitizers and technological innovations in equipment. Conclusions. PDT is a promising treatment method in dentistry, demonstrating high efficacyand safety. Further research is aimed at optimizing treatment protocols, developing personalized approaches, and integrating PDT with other modern technologies.

Sustained release of heparin from PLLA micropartricles for tissue engineering applications

Heparin holds promise for cardiac tissue engineering, but challenges such as hematoma or bleeding and accumulation in tissue caused by excessive release, and short half-life persist. The present study aimed to introduce a reliable mechanism for the prolonged heparin release from a biocompatible polymer carrier. The designed system must ensure that heparin retains its bioactivity over time while preventing premature release. Heparin was encapsulated within poly (L-lactic acid) microparticles using the double emulsion method, with polyvinyl alcohol employed as the stabilizer. The encapsulation efficiency of heparin in the microparticles was calculated as 25.56 %. The functionality of the design was evaluated using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, and Energy Dispersive X-ray Spectroscopy. Drug release and microparticle degradation studies were conducted alongside cell viability tests. The particle sizes ranged from 5 to 10 ± 2.53 μm, with evidence suggesting that heparin promotes the smaller particle formation. The system demonstrated a consistent drug release profile over six weeks with a release rate of 54 % by week two and 97.65 % by week six. The degradation of heparin-loaded microparticles reached less than 50 % by week six, and the loading of heparin did not significantly affect the degradation behavior of the PLLA microparticles in PBS. Furthermore, heparin concentrations between 200 and 400 μg/ml enhanced the viability of Placenta-derived Mesenchymal Stem Cells and H9c2. These findings suggest that the system could be considered as an effective vehicle for sustained heparin delivery across a spectrum of biological applications, particularly in cardiac tissue engineering.