Probing the Impact of Surface Functionalization Module on the Performance of Mitoxantrone Prodrug Nanoassemblies: Improving the Effectiveness and Safety.

Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: a drug module, a modification module, a response module, and a surface functionalization module. Among these modules, surface functionalization is an essential process to enhance the biocompatibility and stability of the nanoassemblies. Here, we selected mitoxantrone (MTO) as the drug module and DSPE-PEG2K as surface functionalization module to develop MTO prodrug nanoassemblies. We systematically evaluated the effect of surface functionalization module ratios (10%, 20%, 40%, and 60% of prodrug, WDSPE-mPEG2000/Wprodrug) on the prodrug nanoassemblies. The results indicated that 40% NPs significantly improved the self-assembly stability and cellular uptake of prodrug nanoassemblies. Compared with MTO solution, 40% NPs showed better tumor specificity and pharmacokinetics, resulting in potent antitumor activity with a good safety profile. These findings highlighted the pivotal role of the surface functionalization module in regulating the performance of mitoxantrone prodrug nanoassemblies for cancer treatment.

The combined impact of Type D personality and depression on cardiovascular events after acute myocardial infarction.

BACKGROUND: Type D personality and depression are the independent psychological risk factors for adverse outcomes in cardiovascular patients. The aim of this study was to examine the combined effect of Type D personality and depression on clinical outcomes in patients suffering from acute myocardial infarction (AMI). METHODS: This prospective cohort study included 3568 patients diagnosed with AMI between February 2017 and September 2018. Type D personality and depression were assessed at baseline, while the major adverse cardiac event (MACE) rate (cardiac death, recurrent non-fatal myocardial infarction, revascularization, and stroke) and in-stent restenosis (ISR) rate were analyzed after a 2-year follow-up period. RESULTS: A total of 437 patients developed MACEs and 185 had ISR during the follow-up period. The Type D (+) depression (+) and Type D (+) depression (-) groups had a higher risk of MACE [95% confidence interval (CI) 1.74-6.07] (95% CI 1.25-2.96) and ISR (95% CI 3.09-8.28) (95% CI 1.85-6.22). Analysis of Type D and depression as continuous variables indicated that the main effect of Type D, depression and their combined effect were significantly associated with MACE and ISR. Moreover, Type D (+) depression (+) and Type D (+) depression (-) emerged as significant risk factors for MACE and ISR in males, while only Type D (+) depression (+) was associated with MACE and ISR in female patients. CONCLUSIONS: These findings suggest that patients complicated with depression and Type D personality are at a higher risk of adverse cardiovascular outcomes. Individual assessments of Type D personality and depression, and comprehensive interventions are required.

Relationship between stressful life events and coronary plaque vulnerability among patients with acute coronary syndrome: a moderated mediation model of psychological distress and physiological indices.

We aimed to explore the association between stressful life events and coronary plaque vulnerability, and examine the moderating effects of psychological distress and physiological indices. A total of 311 patients with acute coronary syndrome (ACS) completed Life Events Scale, Zung Self-Rating Depression and Anxiety Scales. Plaque vulnerability was assessed by in vivo optical coherence tomography (OCT). The regression analysis showed that that stressful life events were independent predictors of plaque vulnerability including lipid-rich plaque (OR = 1.018, 95% CI = 1.005, 1.031, p = 0.005), thin-cap fibroatheroma (TCFA) (OR = 1.038, 95% CI = 1.025, 1.051, p < 0.001), rupture (OR = 1.025, 95% CI = 1.013, 1.037, p < 0.001) and thrombus (OR = 1.030, 95% CI = 1.012, 1.048, p = 0.001). The moderated mediation model revealed that there were significant indirect effects of stressful life events on TCFA through total cholesterol, and the path between stressful life events and TCFA can be moderated by depression. Stressful life events increase the risk of vulnerable plaque in ACS patients. The relationship could be moderated by depression and mediated by physiological indices.

Advancements in Preprocessing and Analysis of Nitrite and Nitrate since 2010 in Biological Samples: A Review.

As a substance present in organisms, nitrite is a metabolite of nitric oxide and can also be ingested. Nitrate is the metabolite of nitrite. Therefore, it is necessary to measure it quickly, easily and accurately to evaluate the health status of humans. Although there have been several reviews on analytical methods for non-biological samples, there have been no reviews focused on both sample preparation and analytical methods for biological samples. First, rapid and accurate nitrite measurement has significant effects on human health. Second, the detection of nitrite in biological samples is problematic due to its very low concentration and matrix interferences. Therefore, the pretreatment plus measuring methods for nitrite and nitrate obtained from biological samples since 2010 are summarized in the present review, and their prospects for the future are proposed. The treatment methods include liquid-liquid microextraction, various derivatization reactions, liquid-liquid extraction, protein precipitation, solid phase extraction, and cloud point extraction. Analytical methods include spectroscopic methods, paper-based analytical devices, ion chromatography, liquid chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography-mass spectrometry and capillary electrophoresis. Derivatization reagents with rapid quantitative reactions and advanced extraction methods with high enrichment efficiency are also included. Nitrate and nitrate should be determined at the same time by the same analytical method. In addition, much exploration has been performed on formulating fast testing through microfluidic technology. In this review, the newest developments in nitrite and nitrate processing are a focus in addition to novel techniques employed in such analyses.

Garlic (Allium sativum L.) in diabetes and its complications: Recent advances in mechanisms of action.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia and impaired islet secretion that places a heavy burden on the global health care system due to its high incidence rate, long disease course and many complications. Fortunately, garlic (Allium sativum L.), a well-known medicinal plant and functional food without the toxicity and side effects of conventional drugs, has shown positive effects in the treatment of diabetes and its complications. With interdisciplinary development and in-depth exploration, we offer a clear and comprehensive summary of the research from the past ten years, focusing on the mechanisms and development processes of garlic in the treatment of diabetes and its complications, aiming to provide a new perspective for the treatment of diabetes and promote the efficient development of this field.

Association between food and nutrients intakes and coronary plaque vulnerability in patients with coronary heart disease: An optical coherence tomography study.

BACKGROUND AND AIMS: Dietary intakes play important roles in the prevention and treatment of coronary heart disease (CHD). Coronary plaque vulnerability is the key mechanism leading to CHD progression. We aimed to explore the association between dietary intakes and plaque vulnerability via optical coherence tomography (OCT). METHODS AND RESULTS: A total of 314 CHD patients were included in this study. Dietary intake status was assessed by semi-quantitative food frequency questionnaire and plaque vulnerability was measured by OCT. The results showed that vegetables were negatively associated with macrophage infiltration, thin cap fibroatheroma (TCFA) and thrombus [odds ratio (OR) = 0.48, 0.38, 0.38, 95% confidence interval (95% CI) = 0.24-0.93, 0.17-0.84, 0.15-0.94, all P < 0.05]; fruits were negatively associated with lipid plaque, TCFA, rupture and thrombus (OR = 0.17, 0.11, 0.12, 0.20, 95% CI = 0.07-0.39, 0.04-0.29, 0.05-0.28, 0.08-0.55, all P < 0.05); salt was positively associated with lipid plaque and TCFA (OR = 2.59, 2.83, 95% CI = 1.14-5.90, 1.23-6.51, all P < 0.05). Regarding nutrients intakes, dietary fiber was negatively associated with macrophage infiltration (OR = 0.34, 95% CI = 0.14-0.85, P = 0.021); folate was negatively associated with lipid plaque, TCFA and rupture (OR = 0.22, 0.16, 0.20, 95% CI = 0.09-0.58, 0.06-0.41, 0.08-0.51, all P < 0.05); vitamin C was negatively associated with TCFA, rupture and thrombus (OR = 0.26, 0.22, 0.05, 95% CI = 0.07-0.95, 0.07-0.65, 0.01-0.25, all P < 0.05); sodium was positively associated with lipid plaque, TCFA, rupture and thrombus (OR = 3.43, 3.96, 2.73, 4.84, 95% CI = 1.51-7.80, 1.66-9.45, 1.18-6.27, 1.76-9.28, all P < 0.05). CONCLUSION: Salt and sodium were dietary risk factors for plaque vulnerability, whereas vegetables, fruits, dietary fiber, folate and vitamin C were dietary protective factors for plaque vulnerability.

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus.

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

Overexpression of MsDREB6.2 results in cytokinin-deficient developmental phenotypes and enhances drought tolerance in transgenic apple plants.

Dehydration-responsive element binding factors (DREBs) play important roles in plant growth, development, and stress signaling pathways in model plants. However, little is known about the function of DREBs in apple (Malus × domestica), a widely cultivated crop that is frequently threatened by drought. We isolated a DREB gene from Malus sieversii (Ledeb.) Roem., MsDREB6.2, and investigated its functions using overexpression analysis and chimeric repressor gene-silencing technology (CRES-T). We identified possible target genes of the protein encoded by MsDREB6.2 using electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP). Overexpression of MsDREB6.2 increased the expression of a key cytokinin (CK) catabolism gene, MdCKX4a, which led to a significant reduction in endogenous CK levels, and caused a decrease in shoot:root ratio in transgenic apple plants. Overexpression of MsDREB6.2 resulted in a decrease in stomatal aperture and density and an increase in root hydraulic conductance (L0 ), and thereby enhanced drought tolerance in transgenic plants. Furthermore, manipulating the level of MsDREB6.2 expression altered the expression of two aquaporin (AQP) genes. The effect of the two AQP genes on L0 was further characterized using the AQP inhibitor HgCl2 . Based on these observations, we conclude that MsDREB6.2 enhances drought tolerance and that its function may be due, at least in part, to its influence on stomatal opening, root growth, and AQP expression. These results may have applications in apple rootstock breeding programs aimed at developing drought-resistant apple varieties.

Prognostic Value of Type D Personality for In-stent Restenosis in Coronary Artery Disease Patients Treated With Drug-Eluting Stent.

OBJECTIVE: To evaluate the predictive value of Type D personality on in-stent restenosis (ISR) rates at 1 and 2 years post-percutaneous coronary intervention (PCI) in patients with coronary artery disease. METHODS: Consecutive patients with coronary artery disease who underwent PCI for drug-eluting stents (n = 173) completed the Type D Scale-14 (DS14) at baseline. Follow-up coronary angiographic evaluation was routinely planned at 1 and 2 years after the procedure. RESULTS: Follow-up coronary angiography was performed in 159 and 112 patients at 1 and 2 years post-PCI, respectively. On multivariate analysis, Type D personality was found to be an independent predictor of ISR at 1 year (odds ratio [OR] = 2.67, 95% confidence interval [CI] = 1.16-6.14, p = .021) and 2 years (OR = 4.92, 95% CI = 1.82-9.60, p = .017) after adjusting for cardiovascular risk factors. However, Type D did not predict ISR when the analysis was performed using the interaction between negative affectivity and social inhibition. The main effect of negative affectivity emerged as a significant risk factor for 1-years (OR = 4.22, 95% CI = 1.18-7.86, p = .034) and 2-year ISR (OR = 6.93, 95% CI = 2.25-11.50, p = .016). CONCLUSIONS: In this study, Type D personality was an independent predictor of ISR at 1 and 2 years post-PCI; the association strengthened with time. The negative affectivity component seems to drive the relationship between Type D and ISR over time. Our findings provide new insights into the mechanisms involved in the association between Type D and adverse clinical outcomes of PCI.

Vitamins supplementation affects the onset of preeclampsia.

Preeclampsia may affect between 2-8% of all pregnancies. It seriously affects maternal health after pregnancy. This meta-analysis was performed to define the efficacy of vitamins supplementation on the risk of preeclampsia. Potential articles were systematically searched on the databases of Pubmed, Embase and Web of Science up to May 2016. Relative risk (RR) and 95% confidence intervals (95%CIs) were used to analyze the relationship of vitamins supplementation with risk of preeclampsia. Cochran Q test was used to test inter-study heterogeneity. Begg's funnel plot was adopted to assess the potential publication bias. 28 eligible studies were selected. Pooled results indicated that vitamins supplementation could reduce the risk of preeclampsia (RR = 0.74, 95%CI = 0.64-0.86). The studies with non-randomized controlled trial (RCT) analysis also suggested the significant relationship of vitamins supplementation with risk of preeclampsia (RR = 0.60, 95%CI = 0.42-0.85). However, negative results were observed in studies with RCT analysis. Subgroup analysis by vitamin type was performed among the studies with RCT analysis. The results indicated that vitamin D supplementation could significantly reduce the risk of preeclampsia (RR = 0.41, 95%CI = 0.22-0.78). Similar results were observed in the studies with multivitamins supplementation (RR = 0.69, 95%CI = 0.51-0.93). Vitamins supplementation could reduce the onset of preeclampsia.

Type D personality, but not Type A behavior pattern, is associated with coronary plaque vulnerability.

Personality traits are associated with major adverse coronary events (MACE) in patients with coronary artery disease (CAD). However, the link between personality traits and intravascular morphology in CAD patients is poorly understood. This study investigated the relationship between personality traits, specifically Type A behavior pattern and Type D personality, and plaque vulnerability. After adjustment for demographic and clinical factors, multivariable regression analysis showed no association between Type A and optical coherence tomography indices. However, Type D personality was independently associated with lipid plaque, thin cap fibroatheroma (TCFA), and fibrous cap thickness. More specifically, negative affectivity of Type D was related to lipid plaque, TCFA and fibrous cap thickness, and social inhibition was associated with plaque rupture. Our results show that Type D personality was associated with plaque vulnerability, independent of clinical factors. Measurement of negative affectivity and social inhibition will increase our understanding of the progressive phase of the plaque vulnerability, which can contribute to the early identification of high risk patients and reduce the incidence of MACE.

Volatile Composition in Two Pummelo Cultivars (Citrus grandis L. Osbeck) from Different Cultivation Regions in China.

This study investigated the composition of volatile compounds in two pummelo cultivars, including 'Shatian' and 'Guanxi', cultivated in different regions of China with the aim of studying the effect of cultivar and cultivation condition on biosynthesis of volatile compounds in pummelo. Volatile compounds were extracted from pummelo juice using head-space microextraction and then analyzed using gas chromatography coupled with mass spectrometry. Results showed that a total of 49 volatile compounds was detected in the study, including 11 aldehydes, 7 alcohols, 3 ketones, 7 esters, 19 terpenes and 2 other volatiles. The 'Guanxi' pummelo cultivar possessed a more complex composition of volatile compounds compared with the 'Shatian' cultivar. Meanwhile, the volatile compounds appeared to exhibit a higher concentration in the 'Guanxi' cultivar samples than the 'Shatian' cultivar. Cluster analysis revealed that the 'Guanxi' cultivar samples from the different regions were grouped together, whereas the 'Shatian' cultivar samples were assembled. Principal component analysis showed that an obvious separation was observed between the 'Guanxi' and 'Shatian' cultivar. However, the 'Shatian-SC15' was significantly separated from the other 'Shatian' cultivar samples. These indicated that cultivar genotype was the primary factor that determined the volatile profile of the pummelo cultivar. Cultivation region might affect the biosynthesis of volatile compounds, resulting in the differentiation of the volatile composition in each pummelo cultivar.

Type D Personality and Coronary Plaque Vulnerability in Patients With Coronary Artery Disease: An Optical Coherence Tomography Study.

OBJECTIVE: To investigate the association between Type D personality and higher incidence of major adverse cardiac events, we used in vivo optical coherence tomography (OCT) to evaluate the association between Type D with coronary plaque characteristics. METHODS: A total of 109 patients who had culprit coronary plaque (s) were included in the study. The Type D construct was analyzed using both the categorized and the continuous approaches. Plaque vulnerability of culprit lesions was measured by OCT. RESULTS: After adjusting for demographic and clinical factors, multivariate analysis demonstrated that Type D was associated with lipid plaque (odds ratio [OR] = 4.87, 95% confidence interval [CI] = 1.41-11.14, p = .025), thin cap fibroatheroma (OR = 3.84, 95% CI = 1.36-10.85, p = .011), and fibrous cap thickness (ß = -1.43, standard error = 0.04, p = .001) analyzed by categorical approach. When analyzing Type D as continuous variable, the negative affectivity component was significantly related to plaque vulnerability, including lipid plaque (OR = 3.43, 95% CI = 1.23-9.52, p = .018), thin cap fibroatheroma (OR = 2.20, 95% CI = 1.10-4.40, p = .026), and fibrous cap thickness (ß = -0.05, standard error = 0.02, p = .030), whereas no associations between the negative affectivity by social inhibition interaction term with OCT indices were found. CONCLUSIONS: The results suggest that plaque characteristics in Type D have more features of plaque vulnerability. The negative affectivity component seems to drive the associations between Type D and vulnerable plaques. These findings provide new insights into the mechanism involved in the association between Type D and major adverse cardiac event.

Design, synthesis and properties of near-infrared molecular switches containing a fluorene ring.

Three molecular switches containing a fluorene ring were designed and synthesized. The introduction of the amino group substituted fluorene ring resulted in the target molecular switches having some optical properties in the near-infrared region. It was demonstrated that the N-substituents on the fluorene rings and the switch units both had great influence on the molecular switch optical properties including the absorption maximum, absorption intensity and fluorescence quantum yield. The open-ring forms and showed obvious solvatochromic behaviour. The closed-ring forms and showed obvious hydrochromic behaviour in MeCN/water binary solvent systems and acidichromic behaviour in MeCN solution with high reversibility. Especially, the distinct off-on fluorescence signal in the near-infrared region using the stimuli of acid means that the designed compounds have great potential application value in the field of biological sensing.

[Calculation of Chlorophyll Fluorescence Characters in Different Light Area to Apple Tree Canopy].

As the basis of plant canopy chlorophyll fluorescence kinetics, light distribution within the canopy determines the interaction relationship between plant physical processes and ecological environment. Spectroscopy technology plays a very important role in building a prediction model of component content to plant canopies. However, there is only limited number of reports about chlorophyll fluorescence properties of different light intensity areas to free spindle apple canopies. In this paper, with the free spindle apple tree as the research object, the canopy space of apple tree was divided into five layers, and six cube grids with 50cm length of side in each layer, and then the light distribution was determined through measuring the light intensity of each cube grids space. firstly, spectrum data and characters of chlorophyll fluorescence were obtained in the different light area; secondly, a differential spectrum curve in red area(680~760 nm) was determined through removing the interference of system error by a differential spectrum; thirdly, relationship model has been established innovatively between the maximum value in red area(680~760 nm) and the chlorophyll fluorescence characters, which has been used as calculation method of chlorophyll fluorescence characters in different light area to apple tree canopy. Fourthly, root mean square error, mean absolute percentage error, mean forecast error were adopted to evaluate the method. The test result shows that the accuracy of the method is all above 80%, which can be the theoretical basis for pruning and getting best light distribution to apple tree canopy.

Comparison of investigation methods of heat injury in grapevine (Vitis) and assessment to heat tolerance in different cultivars and species.

BACKGROUND: In the context of global climate change, heat stress is becoming an increasingly important constraint on grapevine growth and berry quality. There is a need to breed new grape cultivars with heat tolerance and to design effective physiological defenses against heat stress. The investigation of heat injury to plants or tissues under high temperature is an important step in achieving these goals. At present, evaluation methods for heat injury include the gas exchange parameters of photosynthesis, membrane thermostability, chlorophyll content etc.; however, these methods have obvious disadvantages, such as insensitivity, inconvenience and delayed information. An effective and convenient method for investigating the heat injury of grapevine must be developed. RESULTS: In this study, an investigation protocol for a critical temperature (47°C) and heat treatment time (40 min) was developed in detached grape leaves. Based on the results, we found that the OJIP test was superior to measuring electrolyte leakage or photosynthetic O2 evolution for investigating the heat injury of three cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was evaluated through investigating heat injury using the OJIP test. Moreover, the electron transport chain (donor side, acceptor side and reaction center) of PSII in photosynthesis was further investigated. CONCLUSIONS: The OJIP test was a rapid, sensitive and convenient method for investigating heat injury in grapevine. An analysis of PSII function using this method indicated that the acceptor side was less sensitive to heat than was the donor side or the reaction center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild species), heat tolerance varied largely in each genotype group: most wild species and hybrids between V. labrusca and V. vinifera had relatively strong heat tolerance, but most cultivars from V. vinifera had relatively weak heat tolerance.

Preparation and in vitro evaluation of pH and glutathione dual-responsive drug delivery system based on sodium carboxymethyl cellulose.

Stimuli-responsive drug delivery systems based on sodium carboxymethyl cellulose (NaCMC) for drug release encounter inherent challenges. In this research, a novel pH and glutathione (GSH) dual-responsive system, CPT-S-S-NaCMC@ZIF-8/SP-PEG, was constructed. Firstly, the prodrug CPT-S-S-OH was synthesized and combined with NaCMC to form GSH-responsive micelles CPT-S-S-NaCMC, significantly enhancing the drug loading and grafting rates to 63.79 % and 91.99 %, respectively. Subsequently, zinc ions and dimethylimidazole can be assembled into porous materials (ZIF-8) on the surface of the micelles. This system exhibits dual pH-GSH responsiveness and effectively reduces the drug release from 84.76 % to 28.71 % at pH = 7.4. Moreover, incorporating pH-responsive spiropyran (SP)-modified polyethylene glycol (PEG) can reduce drug leakage to 16.09 % at pH = 7.4 and exhibit good fluorescence intensity at 722 nm.

Metabolomic analysis of black sesame seeds: Effects of processing and active compounds in antioxidant and anti-inflammatory properties.

Black sesame seeds (BSS) have been recognized as a functional food due to their nutritional and therapeutic value for many years. In China, BSS is traditionally processed and consumed through two methods, namely, nine steaming nine sun-drying and stir-frying. The present study aimed to evaluate the effects of these processing techniques on the antioxidant and anti-inflammatory activities of BSS. UPLC-QTOF/MS was used for untargeted metabolomics to analyze the composition changes. The results indicated that the different samples had good antioxidant and anti-inflammatory activities, but thermal treatment reduced their activities. Untargeted metabolomics identified a total of 196 metabolites. Molecular docking studies targeting proteins associated with inflammation (iNOS) demonstrated that compounds acting as inhibitors were significantly reduced under both treatments. These results indicate that both nine steaming nine sun-drying and stir-frying lead to substantial loss of antioxidant, anti-inflammatory, and bioactive metabolites in BSS, which provides an important reference for its rational utilization.

Evidential support for garlic supplements against diabetic kidney disease: a preclinical meta-analysis and systematic review.

Garlic (Allium sativum L.) is a popular spice that is widely used for food and medicinal purposes and has shown potential effects on diabetic kidney disease (DKD). Nevertheless, systematic preclinical studies are still lacking. In this meta-analysis and systematic review, we evaluated the role and potential mechanisms of action of garlic and its derived components in animal models of DKD. We searched eight databases for relevant studies from the establishment of the databases to December 2022 and updated in April 2023 before the completion of this review. A total of 24 trials were included in the meta-analysis. It provided preliminary evidence that supplementing with garlic could improve the indicators of renal function (BUN, Scr, 24 h urine volume, proteinuria, and KI) and metabolic disorders (BG, insulin, and body weight). Meanwhile, the beneficial effects of garlic and its components in DKD could be related to alleviating oxidative stress, suppressing inflammatory reactions, delaying renal fibrosis, and improving glucose metabolism. Furthermore, time-dose interval analysis exhibited relatively greater effectiveness when garlic products were supplied at doses of 500 mg kg-1 with interventions lasting 8-10 weeks, and garlic components were administered at doses of 45-150 mg kg-1 with interventions lasting 4-10 weeks. This meta-analysis and systematic review highlights for the first time the therapeutic potential of garlic supplementation in animal models of DKD and offers a more thorough evaluation of its effects and mechanisms to establish an evidence-based basis for designing future clinical trials.

A potential early-atheroprotective target: Irgm1 mediates lymphangiogenesis through LEC autophagy by Tfeb translocation.

Lymphatic dysfunction is a pivotal pathological mechanism underlying the development of early atherosclerotic plaques. Potential targets of lymphatic function must be identified to realize the early prevention and treatment of atherosclerosis (AS). The immunity-related GTPase Irgm1 is involved in orchestrating cellular autophagy and apoptosis. However, the effect of Irgm1 on early AS progression, particularly through alterations in lymphatic function, remains unclear. In this study, we confirmed the protective effect of lymphangiogenesis on early-AS in vivo. Subsequently, an in vivo model of early AS mice with Irgm1 knockdown shows that Irgm1 reduces early atherosclerotic plaque burden by promoting lymphangiogenesis. Given that lymphatic endothelial cell (LEC) autophagy significantly contributes to lymphangiogenesis, Irgm1 may enhance lymphatic circulation by promoting LEC autophagy. Moreover, Irgm1 orchestrates autophagy in LECs by inhibiting mTOR and facilitating nuclear translocation of Tfeb. Collectively, these processes lead to lymphangiogenesis. Thus, this study establishes a link between Irgm1 and early AS, thus revealing a novel mechanism by which Irgm1 exerts an early protective influence on AS within the context of lymphatic circulation. The insights gained from this study have the potential to revolutionize the approach and management of AS onset.