In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.

High Variability of Body Mass Index Is Independently Associated With Incident Heart Failure.

BACKGROUND: Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. METHODS AND RESULTS: In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow-up of 12.5 years. The within-participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant-specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03-1.08], P<0.0001; coefficient of variation: HR, 1.07 [95% CI, 1.04-1.10], P<0.0001). CONCLUSIONS: Longitudinal health records capture BMI fluctuation, which independently predicts HF incidence.

Outdoor artificial light at night exposure and gestational diabetes mellitus: a case-control study.

Objective: This study aims to explore the association between outdoor artificial light at night (ALAN) exposure and gestational diabetes mellitus (GDM). Methods: This study is a retrospective case-control study. According with quantiles, ALAN has been classified into three categories (Q1-Q3). GDM was diagnosed through oral glucose tolerance tests. Conditional logistic regression models were used to evaluate the association between ALAN exposure and GDM risk. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Restricted cubic spline analysis (RCS) was utilized to investigate the no liner association between ALAN and GDM. Results: A total of 5,720 participants were included, comprising 1,430 individuals with GDM and 4,290 matched controls. Pregnant women exposed to higher levels of ALAN during the first trimester exhibited an elevated risk of GDM compared to those with lower exposure levels (Q2 OR = 1.39, 95% CI 1.20-1.63, p < 0.001); (Q3 OR = 1.70, 95% CI 1.44-2.00, p < 0.001). Similarly, elevated ALAN exposure during the second trimester also conferred an increased risk of GDM (second trimester: Q2 OR = 1.70, 95% CI 1.45-1.98, p < 0.001; Q3 OR = 2.08, 95% CI 1.77-2.44, p < 0.001). RCS showed a nonlinear association between ALAN exposure and GDM risk in second trimester pregnancy, with a threshold value of 4.235. Conclusion: Outdoor ALAN exposure during pregnancy is associated with an increased risk of GDM.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria.

Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.

Measuring the quality of transitional care based on elderly patients' experiences with the partners at care transitions measure: a cross-sectional survey.

BACKGROUND: The quality of transitional care is closely related to the health outcomes of patients, and understanding the status of transitional care for patients is crucial to improving the health outcomes of patients. Therefore, this study aims to investigate the quality of transitional care in elderly patients with chronic diseases and analyze its influencing factors, to provide a basis for improving transitional care services. METHODS: This is a cross-sectional study. We used the Chinese version of the Partners at Care Transitions Measure (PACT-M) to survey patients with chronic diseases aged 60 years and older who were about to be discharged from five tertiary hospitals in Henan and Shanxi provinces. We used the mean ± standard deviation to describe the quality of transitional care, t-test or one-way ANOVA, and regression analysis to explore the factors affecting the quality of transitional care for patients. RESULTS: 182 elderly patients with chronic diseases aged ≥ 60 years completed the PACT-M survey. The scores of PACT-M1 and PACT-M2 were (30.69 ± 7.87) and (25.59 ± 7.14) points, respectively. The results of the t-test or one-way ANOVA showed that the patient's marital status, ethnicity, religion, educational level, preretirement occupation, residence, household income per month, and living situation had an impact on the quality of transitional care for elderly patients with chronic diseases (P < 0.05). The results of regression analyses showed that patients' preretirement occupation, social support, and health status were the main influences on the quality of transitional care for elderly patients with chronic diseases (P < 0.05), and they explained 63.1% of the total variance. CONCLUSIONS: The quality of transitional care for older patients with chronic illnesses during the transition from hospital to home needs further improvement. Factors affecting the quality of transitional care included patients' pre-retirement occupation, social support, and health status. We can improve the hospital-community-family tertiary linkage service to provide coordinated and continuous transitional care for patients based on their occupation, health status, and social support to enhance the quality of transitional care and the patient's health.

Long-Term Body Mass Index Variability and Adverse Cardiovascular Outcomes.

Importance: Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by genetic and lifestyle factors. Marked weight gain and loss could be associated with adverse biological processes. Objective: To evaluate the association between BMI variability and incident cardiovascular disease (CVD) events in 2 distinct cohorts. Design, Setting, and Participants: This cohort study used data from the Million Veteran Program (MVP) between 2011 and 2018 and participants in the UK Biobank (UKB) enrolled between 2006 and 2010. Participants were followed up for a median of 3.8 (5th-95th percentile, 3.5) years. Participants with baseline CVD or cancer were excluded. Data were analyzed from September 2022 and September 2023. Exposure: BMI variability was calculated by the retrospective SD and coefficient of variation (CV) using multiple clinical BMI measurements up to the baseline. Main Outcomes and Measures: The main outcome was incident composite CVD events (incident nonfatal myocardial infarction, acute ischemic stroke, and cardiovascular death), assessed using Cox proportional hazards modeling after adjustment for CVD risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, diabetes status, and statin use. Secondary analysis assessed whether associations were dependent on the polygenic score of BMI. Results: Among 92 363 US veterans in the MVP cohort (81 675 [88%] male; mean [SD] age, 56.7 [14.1] years), there were 9695 Hispanic participants, 22 488 non-Hispanic Black participants, and 60 180 non-Hispanic White participants. A total of 4811 composite CVD events were observed from 2011 to 2018. The CV of BMI was associated with 16% higher risk for composite CVD across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These associations were unchanged among subgroups and after adjustment for the polygenic score of BMI. The UKB cohort included 65 047 individuals (mean [SD] age, 57.30 (7.77) years; 38 065 [59%] female) and had 6934 composite CVD events. Each 1-SD increase in BMI variability in the UKB cohort was associated with 8% increased risk of cardiovascular death (HR, 1.08; 95% CI, 1.04-1.11). Conclusions and Relevance: This cohort study found that among US veterans, higher BMI variability was a significant risk marker associated with adverse cardiovascular events independent of mean BMI across major racial and ethnic groups. Results were consistent in the UKB for the cardiovascular death end point. Further studies should investigate the phenotype of high BMI variability.

Effect of quality nursing intervention on wound healing in patients with burns: A meta-analysis.

This meta-analysis aimed to explore the effects of quality nursing intervention on wound healing in patients with burns. A computerised search was conducted for randomised controlled trials (RCTs) on the effect of quality nursing intervention on wound healing in patients with burns in the PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from the date of database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on the inclusion and exclusion criteria. Stata 17.0 software was used for the data analysis. Twenty-nine RCTs involving 2637 patients with burns were included. The meta-analysis revealed that compared with conventional nursing, the implementation of quality nursing intervention in patients with burns significantly shortened the wound healing time (standardised mean difference [SMD] = -2.93, 95% confidence interval [CI]: -3.44 to -2.42, p < 0.001). The incidence of wound infections (odds ratio [OR] = 0.14, 95% CI: 0.07-0.27, p < 0.001) and complications (OR = 0.16, 95% CI: 0.11-0.23, p < 0.001) was also reduced significantly. This meta-analysis shows that applying quality nursing interventions in patients with burns can significantly shorten the wound healing time and reduce the incidence of wound infection and complications, thus promoting early patient recovery.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability.

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.

Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program.

Objective: The development of clinical research informatics tools and workflow processes associated with re-engaging biobank participants has become necessary as genomic repositories increasingly consider the return of actionable research results. Materials and Methods: Here we describe the development and utility of an informatics application for participant recruitment and enrollment management for the Veterans Affairs Million Veteran Program Return Of Actionable Results Study, a randomized controlled pilot trial returning individual genetic results associated with familial hypercholesterolemia. Results: The application is developed in Python-Flask and was placed into production in November 2021. The application includes modules for chart review, medication reconciliation, participant contact and biospecimen logging, survey recording, randomization, and documentation of genetic counseling and result disclosure. Three primary users, a genetic counselor and two research coordinators, and 326 Veteran participants have been integrated into the system as of February 23, 2023. The application has successfully handled 3367 task requests involving greater than 95 000 structured data points. Specifically, application users have recorded 326 chart reviews, 867 recruitment telephone calls, 158 telephone-based surveys, and 61 return of results genetic counseling sessions, among other available study tasks. Conclusion: The development of usable, customizable, and secure informatics tools will become increasingly important as large genomic repositories begin to return research results at scale. Our work provides a proof-of-concept for developing and using such tools to aid in managing the return of results process within a national biobank.

Short time effects of two radiofrequency ablation methods on hypertrophic obstructive cardiomyopathy.

BACKGROUND: Radiofrequency ablation has been applied for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). The two known procedures are percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) and endocardial radiofrequency septal ablation (ERSA). METHODS: This study presents a retrospective analysis of the PIMSRA and ERSA procedures in patients with drug-refractory HOCM. A total of 28 patients participated in the study, with 12 receiving PIMSRA and 16 receiving ERSA. The objective of our study was to compare the short-term effects of these two radiofrequency ablation procedures. RESULTS: At the 30-day follow-up, the PIMSRA group demonstrated a greater reduction in left ventricular outflow tract peak gradient at rest compared to the ERSA group (22.25 [16.72] mmHg versus 47.75 [21.94] mmHg) (p < .01). The values for the PIMSRA group decreased from 99.33 (32.00) mmHg to 22.25 (16.72) mmHg (p < .01), while the ERSA group decreased from 97.75 (30.24) mmHg to 47.75 (21.94) mmHg (p < .01). Only the PIMSRA group exhibited a decrease in mitral regurgitation (MR). The area of MR decreased from 10.13 (4.12) mm2 to 3.65 (2.80) mm2 in the PIMSRA group (p < .01). Additionally, the PIMSRA group experienced reductions in left atrial diameter (LAD) and left ventricular ejection fraction (LVEF)%. The values for LAD changed from 43.58 (7.53) mm to 37.08 (6.92) mm (p = .03), and the values for LVEF% decreased from 65.75 (6.12) pg/mL to 60.83 (4.06) pg/mL (p = .03). CONCLUSION: In terms of the two types of radiofrequency ablation methods used in HOCM, it has been observed that PIMSRA demonstrates a more favorable early treatment effect compared to ERSA.

Eliciting Depression Patients' Preferences for Medication Management: A Protocol for Discrete Choice Experiment.

Introduction: Depression threatens people's lives and imposes huge economic burden. Antidepressant therapy is the first-line treatment for depression, and patient adherence to medication is the key to successful treatment. Depression patients have poor medication adherence, which leads to failure of depression management and significantly poorer clinical outcomes. Incorporating patient preferences into clinical decisions can improve uptake rates, optimize treatment adherence. A discrete choice experiment (DCE) can elicit and quantify individual preferences. Previous DCE studies were conducted in developed countries and ignored the influences of factors other than the medication. This paper outlines an ongoing DCE that aims to (1) explore medication-management-related characteristics that may affect depression patients' adherence to antidepressant, (2) elicit how depression patients consider the trade-offs among different medication managements. Methods: The six attributes and their levels were developed through a literature review, semi-structured interviews and experts and focus group discussions. A fractional factorial design in the software Ngene 1.2 version was used to generate 36 choice sets, and they were divided into 3 blocks. A mixed logit model will be used to explore the patients' preferences, willingness to pay and uptake rate of depression patients for medication management attributes. Results: The final questionnaire consists of three parts. The first is the introduction, which introduces the purpose of the study and the requirements of completing the questionnaire. This was followed by a general information questionnaire, which included sociodemographic characteristics. The last part is DCE tasks, which include 13 DCE choice sets, and each choice set include two alternative and one "opt-out" option. The pilot-test results showed the questionnaire was easy to understand and could be used in formal surveys. Conclusion: Our study shows how the development process of the study can be conducted and reported systematically and rigorously according to the theoretical foundation and design principles in DCE.

USP7 as an emerging therapeutic target: A key regulator of protein homeostasis.

Maintaining protein balance within a cell is essential for proper cellular function, and disruptions in the ubiquitin-proteasome pathway, which is responsible for degrading and recycling unnecessary or damaged proteins, can lead to various diseases. Deubiquitinating enzymes play a vital role in regulating protein homeostasis by removing ubiquitin chains from substrate proteins, thereby controlling important cellular processes, such as apoptosis and DNA repair. Among these enzymes, ubiquitin-specific protease 7 (USP7) is of particular interest. USP7 is a cysteine protease consisting of a TRAF region, catalytic region, and C-terminal ubiquitin-like (UBL) region, and it interacts with tumor suppressors, transcription factors, and other key proteins involved in cell cycle regulation and epigenetic control. Moreover, USP7 has been implicated in the pathogenesis and progression of various diseases, including cancer, inflammation, neurodegenerative conditions, and viral infections. Overall, characterizing the functions of USP7 is crucial for understanding the pathophysiology of diverse diseases and devising innovative therapeutic strategies. This article reviews the structure and function of USP7 and its complexes, its association with diseases, and its known inhibitors and thus represents a valuable resource for advancing USP7 inhibitor development and promoting potential future treatment options for a wide range of diseases.

Dynamic Changes in Long-Standing Multiple Sclerosis Revealed by Longitudinal Structural Network Analysis Using Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: DTI can be used to derive conventional diffusion measurements, which can measure WM abnormalities in multiple sclerosis. DTI can also be used to construct structural brain networks and derive network measurements. However, few studies have compared their sensitivity in detecting brain alterations, especially in longitudinal studies. Therefore, in this study, we aimed to determine which type of measurement is more sensitive in tracking the dynamic changes over time in MS. MATERIALS AND METHODS: Eighteen patients with MS were recruited at baseline and followed up at 6 and 12 months. All patients underwent MR imaging and clinical evaluation at 3 time points. Diffusion and network measurements were derived, and their brain changes were evaluated. RESULTS: None of the conventional DTI measurements displayed statistically significant changes during the follow-up period; however, the nodal degree, nodal efficiency, and nodal path length of the left middle frontal gyrus and bilateral inferior frontal gyrus, opercular part showed significant longitudinal changes between baseline and at 12 months, respectively. CONCLUSIONS: The nodal degree, nodal efficiency, and nodal path length of the left middle frontal gyrus and bilateral inferior frontal gyrus, opercular part may be used to monitor brain changes over time in MS.

Down-regulation of miR-133a-3p protects lung tissue against sepsis-induced acute respiratory distress syndrome by up-regulating SIRT1.

Introduction: MicroRNA-133a-3p (miR-133a-3p) is a potential gene regulator having an important role in the process of inflammation and lung injury. The present work studied the role of miR-133a-3p in sepsis-mediated acute respiratory distress syndrome (ARDS) and the mechanism involved. Material and methods: C57BL/6 mice were selected for the study. Protein expression of Bcl-2, cleaved caspase-3 and Bax was assessed by western blot analysis. Expression of mRNA was assessed by RT-PCR. Effects of inflammation were studied by myeloperoxidase (MPO) activity. Quantification of albumin was done by measuring the albumin conjugated with Evan's blue. The alveolar macrophages were separated from the lungs of mice by the bronchoalveolar lavage procedure and were submitted to sepsis challenge in vitro; the macrophages were treated with lipopolysaccharide (LPS). Results: Treatment of LPS resulted in upregulation of miR-133a-3p in alveolar macrophages. Suppression of miR-133a-3p halted the over-expression of inflammatory cytokines in macrophages and caused remission of histopathologic changes. The ARDS lungs showed a decrease in levels of proinflammatory cytokines and an increase in levels of apoptotic protein, establishing the protective role for miR-133a-3p. The results suggested sirtuin 1 (SIRT1) as a potential target of miR-133a-3p in the macrophages, also showing that expression of SIRT1 was inversely associated with expression of miR-133a-3p. The protective effect of miR-133a-3p down-regulation in LPS-mediated alveolar macrophages and sepsis-induced ARDS could be corrected by a SIRT1 inhibitor. Conclusions: Down-regulation of miR-133a-3p may exert a protective effect on lung tissue against sepsis-mediated ARDS by up-regulating the levels of SIRT1 via suppressing the inflammatory response and inhibiting the cellular apoptosis in lung tissues.

Electroreductive Ring-Opening Carboxylation of 1,3-Oxazolidin-2-ones with CO2 for Accessing ß-Amino Acids.

Electrocarboxylation of the C(sp3)-O bond in 1,3-oxazolidin-2-ones with CO2 to achieve ß-amino acids is developed. The C-O bond in substrates can be selectively cleaved via the single electron transfer on the surface of a cathode or through a CO2• - intermediate under additive-free conditions. A great diversity of ß-amino acids can be obtained in a moderate to excellent yield and readily converted to various biologically active compounds.

Metadherin inhibits chemosensitivity of triple-negative breast cancer to paclitaxel via activation of AKT/GSK-3ß signaling pathway.

Triple-negative breast cancer (TNBC) has an aggressive clinical course, and paclitaxel (PTX)-based chemotherapy remains the main therapeutic drug. Metadherin (MTDH) acts as an oncogene that regulates proliferation, invasion, metastasis, and chemoresistance. This study aimed to investigate whether TNBC chemosensitivity to PTX was related to the MTDH/AKT/glycogen synthase kinase-3beta (GSK-3ß) pathway. Clinical baseline characteristics and immunohistochemistry (IHC) were used to evaluate the expression and prognosis of MTDH and AKT (protein kinase B, PKB) in TNBC patient samples. MTDH shRNA, MTDH overexpression vector, MK-2206, and PTX intervention were used in cell models and mouse tumor-bearing models. Afterwards, mRNA and protein levels were assessed using quantitative real-time polymerase chain reaction and Western blot. Evaluate the level of tumor cell apoptosis and cell cycle using flow cytometry. Cell viability was detected using Cell Count Kit 8. The in vivo imaging system is used to analyze the growth of tumors. We found that higher expression of MTDH or AKT resulted in poorer disease-free survival and a lower Miller-Payne grade. MTDH promotes cell proliferation and increases p-AKT and p-GSK-3ß expression in TNBC cells. Notably, suppression of AKT terminated MTDH overexpression-induced cell proliferation and apoptosis. MTDH knockdown or the AKT inhibitor MK2206 reduced the p-AKT and p-GSK-3ß ratio, reduced cell viability and proliferation, increased cell apoptosis, and increased chemosensitivity to PTX. In vivo, xenograft tumors of an MTDH knockdown+MK2206 group treated with PTX were the smallest compared to other groups. In short, MTDH inhibits TNBC chemosensitivity to PTX by activating the AKT/GSK-3ß signaling pathway.

Sesquiterpenoids and bibenzyl derivative from Dendrobium hercoglossum.

Three new sesquiterpenoids, dendrohercoglin A - C (1-3), and one new bibenzyl derivative, dendronbiline D (4), together with nine known sesquiterpenoids (5-13) were isolated from Dendrobium hercoglossum. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. All the compounds were evaluated for their neuroprotective and anti-inflammatory activities. Compounds 2 and 3 increased the H2O2-damaged SH-SY5Y cell viabilities from 43.3% to 58.6% and 68.4%, respectively. Compound 4 exhibited pronounced anti-inflammatory activity with IC50 value of 9.5 ± 0.45 µM which was superior to the reference compound quercetin (IC50: 15.7 ± 0.89 µM).

Identification of volatile compounds and their bioactivities from unpolar fraction of Alpinia oxyphylla Miq. and mining key genes of nootkatone biosynthesis.

In this study, analysis of the chemical constituents and bioactivities of the unpolar fractions [petroleum ether (PE) and chloroform (C)] of fruits and leaves of Alpinia oxyphylla Miq. were carried out, as well as the bioactivities of the main compounds nootkatone and valencene. From PE and C fractions of the fruits, and PE fraction of the leaves, 95.80%, 59.30%, and 82.11% of the chemical constituents respectively were identified by GC-MS. Among these identified compounds, nootkatone was the main compound in all of three fractions, while valencene was the second main compound in the PE fractions of the fruits and leaves. The bioactivities results showed that all of the fractions and the major compound nootkatone showed tyrosinase inhibitory, as well as inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. While valencene only presented inhibitory activity on NO production in RAW264.7 cells. The critical genes involved in nootkatone biosynthesis in A. oxyphylla were identified from the public transcriptome datasets, and protein sequences were preliminarily analyzed. Our studies develop the usage of the unpolar fractions of A. oxyphylla, especially its leaves as the waste during its production, and meanwhile provide the gene resources for nootkatone biosynthesis.