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The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague–Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway. [ABSTRACT FROM AUTHOR]

The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague–Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway. [ABSTRACT FROM AUTHOR]

Evidence on the influence of patient characteristics on HbA1c treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA1c treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium–glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA1c reduction ≥ 1% at 6th month, HbA1c goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA1c, patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA1c treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications. [ABSTRACT FROM AUTHOR]

Researches had proven that the occurrence of bladder cancer (BC) is much higher in men than those in women, which induced us to explore whether androgen plays a role in BC. A total of 147 patients who were diagnosed with primary BC by histopathological biopsy were included. Meanwhile 154 non-tumor patients were matched as the control group. The continuous variables were expressed as median (interquartile range, IQR) and compared by Mann–Whitney U test, for the reason that the data were not matched the requirementsthe of normal test. A Chi-square test was used to compare the categorical variables, which were expressed as frequency (percentage). Meanwhile univariate and multivariate logistic regression was done to further evaluating the potential independent factor of BC. P < 0.05 was considered statistically significant. Univariate multivariate analyse showed significant difference between two groups in hemoglobin (OR 0.979, 95% CI 0.968–0.991, P < 0.001), hypertension (OR 3.026, 95% CI 1.731–5.288, P < 0.001), diabetes (OR 4.294, 95% CI 1.887–9.771, P = 0.001) and smoking (OR 1.729, 95% CI 1.096–2.729, P = 0.019). Furthermore, multivariate logistic regression analysis was conducted to eliminate the interference of confounding factors, which showed that testosterone seems to be great correlated with the BC (OR 1.002, 95% CI 1.000–1.003, P = 0.017). Similar results were also found in hemoglobin (OR 0.981, 95% CI 0.968–0.993, P = 0.002), hypertension (OR 2.780, 95% CI 1.509–5.120, P = 0.001), diabetes (OR 3.313 95% CI 1.373–7.991, P = 0.008) and smoking (OR 1.938, 95% CI 1.184–3.174, P = 0.009). As a conclusion, our study showed that there was significant correlation between serum total testosterone levels and the occurrence of BC, similar results were shown in hemoglobin, hypertension, diabetes and smoking. [ABSTRACT FROM AUTHOR]

Type-2 diabetes mellitus (T2DM) is a medical condition in which oral medications avail to patients to curb their hyperglycaemia after failed dietary therapy. However, individual responses to the prescribed pharmacotherapy may differ due to their clinical profiles, comorbidities, lifestyles and medical adherence. One approach is to identify similar patients within the same community to predict their likely response to the prescribed diabetes medications. This study aims to present an evidence-based diabetes medication recommendation system (DMRS) underpinned by patient similarity analytics. The DMRS was developed using 10-year electronic health records of 54,933 adult patients with T2DM from six primary care clinics in Singapore. Multiple clinical variables including patient demographics, comorbidities, laboratory test results, existing medications, and trajectory patterns of haemoglobin A1c (HbA1c) were used to identify similar patients. The DMRS was evaluated on four groups of patients with comorbidities such as hyperlipidaemia (HLD) and hypertension (HTN). Recommendations were assessed using hit ratio which represents the percentage of patients with at least one recommended sets of medication matches exactly the diabetes prescriptions in both the type and dosage. Recall, precision, and mean reciprocal ranking of the recommendation against the diabetes prescriptions in the EHR records were also computed. Evaluation against the EHR prescriptions revealed that the DMRS recommendations can achieve hit ratio of 81% for diabetes patients with no comorbidity, 84% for those with HLD, 78% for those with HTN, and 75% for those with both HLD and HTN. By considering patients' clinical profiles and their trajectory patterns of HbA1c, the DMRS can provide an individualized recommendation that resembles the actual prescribed medication and dosage. Such a system is useful as a shared decision-making tool to assist clinicians in selecting the appropriate medications for patients with T2DM. [ABSTRACT FROM AUTHOR]

To predict disease outcome in muscle-invasive bladder cancer (MIBC), we constructed a prognostic autophagy-related (PAR) lncRNA signature. Comprehensive bioinformatics analyses were performed using data from TCGA and GTEx databases. Univariate Cox, and least absolute shrinkage and selection operator regression analyses were also performed, based on differentially expressed genes, to identify PAR-related lncRNAs to establish the signature. Furthermore, the Kaplan–Meier OS curve and receiver operating characteristic curve analyses were performed and a nomogram was constructed, all of which together confirmed the strong predictive ability of the constructed signature. Patients with MIBC were then divided into high- and low-risk groups. Gene enrichment and immune infiltration analyses revealed the potential mechanisms in MIBC. We also further evaluated the signature of molecules related to immune checkpoints and the sensitivity toward chemotherapeutic agents and antitumor-targeted drugs to find better treatment prescriptions. We identified a number of PAR-related lncRNA signatures, including HCP5, AC024060.1, NEAT1, AC105942.1, XIST, MAFG-DT, and NR2F1-AS1, which could be valuable prognostic tools to develop more efficient, individualized drug therapies for MIBC patients. [ABSTRACT FROM AUTHOR]

This study looked at novel data sources for cardiovascular risk prediction including detailed lifestyle questionnaire and continuous blood pressure monitoring, using ensemble machine learning algorithms (MLAs). The reference conventional risk score compared against was the Framingham Risk Score (FRS). The outcome variables were low or high risk based on calcium score 0 or calcium score 100 and above. Ensemble MLAs were built based on naive bayes, random forest and support vector classifier for low risk and generalized linear regression, support vector regressor and stochastic gradient descent regressor for high risk categories. MLAs were trained on 600 Southeast Asians aged 21 to 69 years free of cardiovascular disease. All MLAs outperformed the FRS for low and high-risk categories. MLA based on lifestyle questionnaire only achieved AUC of 0.715 (95% CI 0.681, 0.750) and 0.710 (95% CI 0.653, 0.766) for low and high risk respectively. Combining all groups of risk factors (lifestyle survey questionnaires, clinical blood tests, 24-h ambulatory blood pressure and heart rate monitoring) along with feature selection, prediction of low and high CVD risk groups were further enhanced to 0.791 (95% CI 0.759, 0.822) and 0.790 (95% CI 0.745, 0.836). Besides conventional predictors, self-reported physical activity, average daily heart rate, awake blood pressure variability and percentage time in diastolic hypertension were important contributors to CVD risk classification. [ABSTRACT FROM AUTHOR]

Chloroplast genomes have been widely considered an informative and valuable resource for molecular marker development and phylogenetic reconstruction in plant species. This study evaluated the complete chloroplast genomes of the traditional Chinese medicine Gleditsia sinensis and G. japonica, an adulterant of the former. The complete chloroplast genomes of G. sinensis and G. japonica were found to be of sizes 163,175 bp and 162,391 bp, respectively. A total of 111 genes were identified in each chloroplast genome, including 77 coding sequences, 30 tRNA, and 4 rRNA genes. Comparative analysis demonstrated that the chloroplast genomes of these two species were highly conserved in genome size, GC contents, and gene organization. Additionally, nucleotide diversity analysis of the two chloroplast genomes revealed that the two short regions of ycf1b were highly diverse, and could be treated as mini-barcode candidate regions. The mini-barcode of primers ZJ818F-1038R was proven to precisely discriminate between these two species and reflect their biomass ratio accurately. Overall, the findings of our study will shed light on the genetic evolution and guide species identification of G. sinensis and G. japonica. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

High-throughput sequencing of chloroplast genomes has been used to gain insight into the evolutionary relationships of plant species. In this study, we sequenced the complete chloroplast genomes of four species in the Meconopsis genus: M. racemosa, M. integrifolia (Maxim.) Franch, M. horridula and M. punicea. These plants grow in the wild and are recognized as having important medicinal and ornamental applications. The sequencing results showed that the size of the Meconopsis chloroplast genome ranges from 151864 to 153816 bp. A total of 127 genes comprising 90 protein-coding genes, 37 tRNA genes and 8 rRNA genes were observed in all four chloroplast genomes. Comparative analysis of the four chloroplast genomes revealed five hotspot regions (matK, rpoC2, petA, ndhF, and ycf1), which could potentially be used as unique molecular markers for species identification. In addition, the ycf1 gene may also be used as an effective molecular marker to distinguish Papaveraceae and determine the evolutionary relationships among plant species in the Papaveraceae family. Futhermore, these four genomes can provide valuable genetic information for other related studies. [ABSTRACT FROM AUTHOR]

The role of angiotensin receptor blocker in wound healing and cutaneous fibrosis has become a hotspot in recent years. We have developed a losartan cream that is comparable to triamcinolone ointment in inhibiting scarring. Considering the effects of chitosan and asiaticoside on wound healing and scarring, we added them to the losartan cream this time and improved the formula, expecting to get a better anti-scarring effect. The effects of creams were investigated on mouse scar model with triamcinolone ointment, onion extract gel, and commercial asiaticoside cream set as positive controls. A preliminary exploration of the mechanism involved in TGF-β/Smad pathway was performed in vivo and in vitro. With all results of anti-scarring, the compound losartan cream (containing chitosan, asiaticoside, and losartan) shows the best effect, followed by the chitosan asiaticoside cream. The treatment of the compound losartan cream inhibited expression of TGF-β1, collagen, and Smads, and decreased phosphorylation of Smad in vivo. These inhibitory effects were also confirmed in vitro. Our findings indicated that the compound losartan cream could inhibit scarring via TGF-β/Smad pathway. This cream might be an effective option for scar treatment. [ABSTRACT FROM AUTHOR]

Dengue fever is a mosquito-borne disease caused by the dengue virus. Aedes aegypti (Ae. Aegypti) is considered the primary vector of Dengue virus transmission in Yunnan Province, China. With increased urbanization, Ae. aegypti populations have significantly increased over the last 20 years. Despite all the efforts that were made for controlling the virus transmission, especially on border areas between Yunnan and Laos, Vietnam, and Myanmar (dengue-endemic areas), the epidemic has not yet been eradicated. Thus, further understanding of the genetic diversity, population structure, and invasive strategies of Ae. aegypti populations in the border areas was vital to uncover the vector invasion and distribution dynamic, and essential for controlling the infection. In this study, we analyzed genetic diversity and population structure of eight adult Ae. Aegypti populations collected along the border areas of Yunnan Province in 2017 and 2018. Nine nuclear microsatellite loci and mitochondrial DNA (mtDNA) sequences were used to achieve a better understanding of the genetic diversity and population structure. One hundred and fourteen alleles were found in total. The polymorphic information content value, together with the expected heterozygosity (He) and observed heterozygosity (Ho) values showed high genetic diversity in all mosquito populations. The clustering analysis based on Bayesian algorithm, the UPGMA and DAPC analysis revealed that all the eight Ae. aegypti populations can be divided into three genetic groups. Based on the mtDNA results, all Ae. aegypti individuals were divided into 11 haplotypes. The Ae. aegypti populations in the border areas of Yunnan Province presented with high genetic diversity, which might be ascribed to the continuous incursion of Ae. aegypti. [ABSTRACT FROM AUTHOR]

Non-thermal plasma (NTP) is a promising biomedical tool for application to wound healing. However, there is limited scientific evidence that confirms its efficacy to inhibit scar formation. This study aims to investigate the role of non-thermal plasma in scar formation. Two full-thickness dorsal cutaneous wounds of rats were treated with either a non-thermal helium plasma jet or helium. It was determined that the non-thermal plasma jet accelerated the wound healing process from 5 days after surgery (day 5: 41.27% ± 2.351 vs 54.7% ± 5.314, p < 0.05; day 7: 56.05% ± 1.881 vs 75.28% ± 3.914, p < 0.01; day 14: 89.85% ± 2.991 vs 98.07% ± 0.839, p < 0.05). The width of the scars for the NTP group was narrower than those of control group (4.607 ± 0.416 mm vs 3.260 ± 0.333 mm, p < 0.05). In addition, a lower level of TGF-β1, p-Smad2 and p-Smad3 were detected in the NTP treated wounds (p < 0.05, p < 0.01 and p < 0.01). As expected, α-SMA was also significantly decreased in the NTP treatment group (p < 0.01). Moreover, the expression of type I collagen and the proportion of type I to III collagen were lower in the NTP group (p < 0.05). The results of the study suggest that NTP may play a potential role in scar formation by inhibiting the TGF β1 signal pathway and reducing the levels of α-SMA and type I collagen, and may have clinical utility in the future. [ABSTRACT FROM AUTHOR]

Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo. In addition, a significantly high proliferation level of both transplanted stem cells and resident cardiomyocytes was observed in the TSCs group. These findings primary revealed the therapeutic potential of TSCs in transplantation therapy for MI. [ABSTRACT FROM AUTHOR]

Iron (hydr)oxides are ubiquitous earth materials that have high adsorption capacities for toxic elements and degradation ability towards organic contaminants. Many studies have investigated the reactivity of synthetic magnetite, while little is known about natural magnetite. Here, we first report the reactivity of natural magnetites with a variety of elemental impurities for catalyzing the decomposition of H2O2 to produce hydroxyl free radicals (•OH) and the consequent degradation of p-nitrophenol (p-NP). We observed that these natural magnetites show higher catalytic performance than that of the synthetic pure magnetite. The catalytic ability of natural magnetite with high phase purity depends on the surface site density while that for the magnetites with exsolutions relies on the mineralogical nature of the exsolved phases. The pleonaste exsolution can promote the generation of •OH and the consequent degradation of p-NP; the ilmenite exsolution has little effect on the decomposition of H2O2, but can increase the adsorption of p-NP on magnetite. Our results imply that natural magnetite is an efficient catalyst for the degradation of organic contaminants in nature. [ABSTRACT FROM AUTHOR]