Exosomes originating from MSCs stimulated with TGF-ß and IFN-γ promote Treg differentiation.

Mesenchymal stem cells (MSCs) have been approved as a cellular drug for the treatment of a variety of immune-related diseases by the government of many countries'. Previous investigations, including ours, have shown that exosomes secreted by MSCs (MSC-ex) are one of the main factors responsible for the therapeutic effect of MSCs. However, the immune modulation activities and the contents of MSC-ex derived from cells under different incubation conditions differ dramatically. Therefore, the optimal way to ensure effectiveness is by identifying and preparing MSC-ex with confirmed potent immunosuppressive activity. The aim of this study was to investigate and analyze the composition and function of MSC-ex secreted by MSCs stimulated by different cytokines to obtain exosomes with more potent immunosuppressive activity. To achieve this aim, umbilical cord-derived MSCs were treated with PBS, TGF-ß, IFN-γ, or TGF-ß plus IFN-γ for 72 hr. Then, exosomes were isolated from the culture supernatants. Common exosome markers, such as CD9, CD63, and CD81, were detected and analyzed by FCM. At the same time, the TGF-ß, IFN-γ, IDO, and IL-10 content in exosomes was detected, and the influence of exosmes from defferent groups on the induction of mononuclear cell transformation into Tregs was analyzed via FCM. Our results show that the TGF-ß combined with IFN-γ exosome group more effectively promoted the transformation of mononuclear cells to Tregs, and the analysis showed that IDO may play an important role. This study might provide a novel strategy to treat GVHD as well as other immune-associated disorders.

Mechanically and Thermally Guided, Honeycomb-like Nanocomposites with Strain-Insensitive High Thermal Conductivity for Stretchable Electronics.

Thermal management materials have become increasingly crucial for stretchable electronic devices and systems. Drastically different from conventional thermally conductive materials, which are applied at static conditions, thermal management materials for stretchable electronics additionally require strain-insensitive thermal conductivity, as they generally undergo cyclic deformation. However, realizing such a property remains challenging mainly because conventional thermally conductive polymer composites generally lack a mechanically guided design. Here, we report a honeycomb-like nanocomposite with a three-dimensional (3D) thermally conductive network fabricated by an arrayed ice-templating technique followed by elastomer infiltration. The hexagonal honeycomb-like structure with thin, compact walls (≈ 40 µm) endows our composite with a high through-plane thermal conductivity (≈ 1.54 W m-1 K-1) at an ultralow boron nitride nanosheet (BNNS) loading (≈ 0.85 vol %), with an enhancement factor of thermal conductivity up to 820% and thermal-insensitive strain up to 200%, which are 2.7 and 2 times higher than those reported in the literature. We report an intelligent strategy for the development of advanced thermal management materials for high-performance stretchable electronics.

2022 Shandong Province university medical technical skills competition nursing track: An effective project to improve core competencies of nursing students.

Background: The core competencies of nursing students have gradually become the focus of attention of nursing educators. Nursing skills competitions are an important form of educational and teaching activity in universities and the nursing track at the Shandong Provincial University Students' Medical Technical Skills Competition gives nursing students an opportunity to demonstrate their clinical skills and knowledge. This study aims to describe the organisation and procedures of the nursing track, analyse the competition results and explore the impact the competition has on the core competencies of the nursing students. This will provide new ideas for future nursing professional education. Methods: Statistical analysis of the competition results was performed as a means of understanding the current status of theoretical knowledge and clinical skills of nursing students in Shandong Province. The impact of the competition on the core competencies of participating students was analysed by distributing questionnaires to universities in Shandong Province that participated in the competition. Results: 14 universities with nursing programmes participated in the competition, including eight public universities and six private universities. 220 questionnaires were distributed to nursing students at the participating universities and 218 were ultimately included, demonstrating an efficiency rate of 99.09%. Conclusions: The 2022 nursing track included the addition of a comprehensive written examination as a means of judging the competencies of nursing students in Shandong Province from a variety of aspects. Skills competitions are effective for improving the core competencies of nursing students and they will become an important means for nursing educators to reform education and improve the core competencies of nursing students in the future.

Critical care pharmacy service provision and workforce in adult extracorporeal membrane oxygenation centres: a multicentre cross-sectional survey.

BACKGROUND: There is good evidence describing pharmacy workforce and service provision in general critical care units. However, no data exist from adult extracorporeal membrane oxygenation (ECMO) centres. AIM: To describe workforce characteristics, pharmacy service provision, and pharmaceutical care activities in critical care units (CCUs) providing an adult ECMO service in the United Kingdom (UK) and compare to national staffing standards for CCUs. METHOD: We conducted a multicentre, cross-sectional electronic survey inviting one pharmacy professional response per UK ECMO centre. We collated information on workforce, service provision, and pharmaceutical care activities provided by pharmacy teams in adult CCUs with an ECMO service. RESULTS: The survey response rate was 90.9%: representatives of 10/11 tertiary hospitals providing ECMO services responded. Median critical care pharmacist to critical care bed was 1:12.1 (IQR: 1:9.4-1:14.9). Most centres (90.0%) did not meet national standards for pharmacy professionals to critical care bed staffing ratios for weekday services. Total critical care beds covered by the critical care pharmacy team varied across the UK: median (IQR) - 45 (37-80) beds. Two centres funded pharmacist time for ECMO activity, and one centre funded a pharmacy technician post. Median peak ECMO activity was 4 ECMO patients in a single day (IQR: 3-5). Most respondents reported reduced pharmacy service at weekends compared to weekday, with limited on-site support. CONCLUSION: Most responding ECMO centres in the UK reported pharmacy staffing ratios below nationally agreed critical care standards. There was high variability in clinical pharmacy services to ECMO patients over 7 days.

Characteristics of macroscopic sleep structure in patients with mild cognitive impairment: a systematic review.

Objectives: Conducting a systematic analysis of objective measurement tools to assess the characteristics of macroscopic sleep architecture in patients with mild cognitive impairment (MCI), amnestic MCI (aMCI), and non-amnestic MCI (naMCI) in order to provide sleep disorder guidance for MCI patients. Methods: PubMed, EMbase, Web of Science, Cochrane Library, CNKI, SinoMed, Wanfang Data, and VIP Data were examined to find literature relating to sleep in patients with MCI, aMCI, and naMCI, with a search time frame of build to April 2023. Following independent literature screening, data extraction, and quality evaluation by two researchers, statistical analysis was performed using RevMan 5.4 software. Results: Twenty-five papers with 1,165 study subjects were included. Patients with MCI and aMCI were found to have altered total sleep time (TST), reduced sleep efficiency (SE), more wake-time after sleep onset (WASO), longer sleep latency (SL), a higher proportion of N1 stage and a lower proportion of N2 and N3 stage. naMCI was only found to have statistically significant differences in WASO. Conclusions: The results of this study provide evidence for macroscopic sleep architecture abnormalities among MCI patients with sleep disorders. Maintaining a normal sleep time, improving SE, and reducing sleep fragmentation may have an association with a slowed development of cognitive impairment. Further exploration is required of the effects each component of macroscopic sleep structure after the intervention has on altered sleep disturbance and cognition in MCI, aMCI, and naMCI. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023401937, identifier: CRD42023401937.

Spatial evolution of global petrochemical risk and the influence by industrialization.

The petrochemical industry is an integral contributor to the global economy and plays a critical role in improving the lives of people worldwide. However, its development has also led to frequent accidents, and the evolution and global impact of these risks have not been adequately assessed. This study is aimed at quantitatively analyzing the current state of petrochemical risk and its impact on industrial development in 58 coastal countries (regions) worldwide by identifying petrochemical risk impact indicators and constructing threshold regression models. We showed that the global petrochemical risk has been unevenly decreasing in recent years. In some countries (regions), the petrochemical risk remains unchanged or is increasing; in particular, coastal provinces of China need to address this issue. Moreover, when industrialization and economic development levels are < 53.6 and 34,918.4 USD/person, respectively, petrochemical accidents negatively affect industrial development; however, above these thresholds, they do not impact industrial development. Coastal areas of China and some developing countries are far below these thresholds. Therefore, the risk from petrochemicals remains a critical factor affecting industrial development in countries with low industrialization levels.

Textural features of the frontal white matter could be used to discriminate amnestic mild cognitive impairment patients from the normal population.

OBJECTIVE: We aim to develop a radiomics model based on 3-dimensional (3D)-T1WI images to discriminate amnestic mild cognitive impairment (aMCI) patients from the normal population by measuring changes in frontal white matter. METHODS: In this study, 126 patients with aMCI and 174 normal controls (NC) were recruited from the local community. All subjects underwent routine magnetic resonance imaging examination (including 3D-T1WI ). Participants were randomly divided into a training set (n = 242, aMCI:102, NC:140) and a testing set (n = 58, aMCI:24, NC:34). Texture features of the frontal lobe were extracted from 3D-T1WI images. The least absolute shrinkage and selection operator (LASSO) was used to reduce feature dimensions and develop a radiomics signature model. Diagnostic performance was assessed in the training and testing sets using the receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC), sensitivity, and specificity were also calculated. The efficacy of the radiomics model in discriminating aMCI patients from the normal population was assessed by decision curve analysis (DCA). RESULTS: A total of 108 frontal lobe texture features were extracted from 3D-T1WI images. LASSO selected 58 radiomic features for the final model, including log-sigma (n = 18), original (n = 8), and wavelet (n = 32) features. The performance of radiomic features extracted from 3D T1 imaging for distinguishing aMCI patients from controls was: in the training set, AUC was 1.00, and the accuracy, sensitivity, and specificity were 100%, 98%, and 100%, respectively. In the testing set, AUC was 0.82 (95% CI:0.69-0.95), and the accuracy, sensitivity, and specificity were 69%, 92%, and 55%, respectively. The DCA demonstrated that the model had favorable clinical predictive value. CONCLUSIONS: Textural features of white matter in the frontal lobe showed potential for distinguishing aMCI from the normal population, which could be a surrogate protocol to aid aMCI screening in clinical setting.

Spectral computed tomography parameters could be surrogate imaging markers to detect early perfusion changes in diabetic kidneys.

Background: Kidney microvasculopathy is the baseline pathophysiological feature of diabetic kidney disease (DKD). We aimed to evaluate the spectral computed tomography (CT) parameters for detecting renal perfusion changes among diabetic patients. Methods: From August 2020 to June 2022, 34 patients (age, 57.7±10.7 years; male, 20) clinically diagnosed with type 2 diabetes mellitus (DM) and 19 DM-free individuals (age, 48.1±16.9 years; male, 12) were selected for analysis. The series participants formed the DM group and control group, respectively. Spectral parameters, including effective atomic number (Zeff), iodine density (ID), normalized iodine density (NID) and the slope of the energy spectrum curves (λ), between the 2 groups were analyzed using independent samples t-test. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic performance of spectral parameters for detecting renal perfusion changes. Results: The results indicate that in both cortical and medullary phases, the values of Zeff, ID, NID, and λ40-70 for the renal cortex of the DM group were significantly higher than those in the control group (P<0.05). In the cortex phase, the diagnostic efficacy of cortical spectral CT parameters discriminating DM patients from controls was as follows: the area under ROC curve (AUC) of ID value was 0.816 [95% confidence interval (CI): 0.679-0.921] at the optimal cutoff value 4.14, the AUC of Zeff value was 0.800 (95% CI: 0.668-0.901) at the optimal cutoff value 9.26, the AUC of λ40-70 value was 0.822 (95% CI: 0.675-0.918) at the optimal cutoff value 8.26, and the AUC of NID value was 0.851 (95% CI: 0.684-0.926) at the optimal cutoff value 0.37. In medullary phase: the AUC of ID value was 0.769 (95% CI: 0.617-0.846) at the optimal cutoff value 5.08, the AUC of Zeff value was 0.763 (95% CI: 0.614-0.837) at the optimal cutoff value 9.58, the AUC of λ40-70 value was 0.766 (95% CI: 0.617-0.839) at the optimal cutoff value 10.07, and the AUC of NID value was 0.79 (95% CI: 0.623-0.855) at the optimal cutoff value 1.37. Conclusions: Spectral CT could serve as an alternative protocol for the early identification of kidney injury in diabetic patients.

The relationship between the prefrontal cortex and limb motor function in stroke: A study based on resting-state functional near-infrared spectroscopy.

BACKGROUND: With the ageing of the world population, the incidence of stroke has been increasing annually, becoming a public health problem affecting adult health. Limb motor dysfunction is one of the common complications of stroke and an important factor in disability. Therefore, restoring limb function is an important task in current rehabilitation. Accurate assessment of motor function in stroke patients is the basis for formulating effective rehabilitation strategies. With the development of neuroimaging technology, scholars have begun to study objective evaluation methods for limb motor dysfunction in stroke to determine reliable neural biomarkers to accurately identify brain functional activity and its relationship with limb motor function. The prefrontal cortex (PFC) plays an important role in motor control and in response to motor state changes. Our previous study found that the PFC network characteristics of stroke patients are related to their motor function status and the topological properties of the PFC network under resting state can predict the motor function of stroke patients to some extent. Therefore, this study used functional near-infrared spectroscopy (fNIRS) to evaluate prefrontal neuroplasticity markers and the relationships between such neural markers and limb motor function in stroke patients with limb motor dysfunction, which could be helpful to further clarify the relationship between brain neuroplasticity and cerebral haemodynamics. At the same time, through accurate and objective means of evaluation, it could be helpful for clinicians to formulate and optimize individualized rehabilitation treatment plans and accurately determine the rehabilitation efficacy and prognosis. METHODS: This study recruited 17 S patients with limb motor dysfunction and 9 healthy subjects. fNIRS was used to collect 22 channels of cerebral blood oxygen signals in the PFC in the resting state. The differences in prefrontal oxygenated haemoglobin (HbO) and deoxygenated haemoglobin (HbR) concentrations were analysed between stroke patients and healthy subjects, and the lateralization index (LI) of HbO in stroke patients was also calculated. Pearson's correlation analysis was performed between the LI and the scores of the Fugl-Meyer Assessment Scale (FMA) of motor function in stroke patients. RESULTS: The results found that the prefrontal HbO concentration was significantly decreased in stroke patients with limb motor dysfunction compared with healthy subjects, and there was a significant, positive correlation between the LI of the PFC and FMA scores in stroke patients. CONCLUSION: These study results showed that stroke can cause cerebral haemodynamic changes in the PFC, and the functional imbalance of the left and right PFC in the resting state is correlated with the severity of limb motor dysfunction. Furthermore, we emphasize that the cerebral haemodynamic activity reflected by fNIRS could be used as a reliable neural biomarker for assessing limb motor dysfunction in stroke.

Association analysis of agronomic traits and construction of genetic networks by resequencing of 306 sugar beet (Beta vulgaris L.) lines.

Due to the relatively brief domestication history of sugar beet (Beta vulgaris ssp. vulgaris), our understanding of the genomic diversity and functional genes in its cultivars is limited, resulting in slow breeding progress. To address this issue, a total of 306 germplasm materials of major cultivars and breeding lines from China, the USA, and Europe were selected for genome resequencing. We investigated population structure and genetic diversity and performed selective scanning of genomic regions, identifying six novel genes associated with important agronomic traits: the candidate genes DFAX2 and P5CS for skin roughness; the candidate genes FRO5, GL24, and PPR91 for root yield and sugar yield, and the pleiotropic candidate gene POLX for flourishing growth vigour, plant height, crown size, flesh coarseness, and sugar yield. In addition, we constructed a protein-protein interaction network map and a phenotype-gene network map, which provide valuable information for identifying and characterizing functional genes affecting agronomic traits in sugar beet. Overall, our study sheds light on the future improvement of sugar beet agronomic traits at the molecular level.

Reducing Medication Problems among Minority Individuals with Low Socioeconomic Status through Pharmacist Home Visits.

Introduction: In this study, pharmacists conducted home visits for individuals of medically underserved populations in Taiwan (i.e., socioeconomically disadvantaged individuals, middle-aged or older adults, and individuals living alone, with dementia, or with disabilities) to understand their medication habits. We quantified medication problems among various groups and investigated whether the pharmacist home visits helped to reduce the medication problems. Materials and Methods: From April 2016 to March 2019, pharmacists visited the homes of the aforementioned medically underserved individuals in Taipei to evaluate their drug-related problems and medication problems. Age, living alone, diagnoses of dementia or disabilities, and socioeconomic disadvantages contributed significantly to inadequate disease and medical treatment knowledge and self-care skills as well as lifestyle inappropriateness among patients. The patients who were living alone and socioeconomically disadvantaged stored their drugs in inappropriate environments. Results: After the pharmacists visited the patients' homes twice, the patients improved considerably in their disease and medical treatment knowledge, self-care skills, and lifestyles (p < 0.001). Problems related to the uninstructed reduction or discontinuation of drug use (p < 0.05) and use of expired drugs (p < 0.001) were also mitigated substantially. Discussion and conclusion: Through the home visits, the pharmacists came to fully understand the medicine (including Chinese medicine) and health food usage behaviors of the patients and their lifestyles, enabling them to provide thorough health education. After the pharmacists' home visits, the patients' drug-related problems were mitigated, and their knowledge of diseases, drug compliance, and drug storage methods and environments improved, reducing drug waste. Our findings can help policymakers address the medication problems of various medically underserved groups, thereby improving the utilization of limited medical resources.

Genomic and transcriptomic-based analysis of agronomic traits in sugar beet (Beta vulgaris L.) pure line IMA1.

Sugar beet (Beta vulgaris L.) is an important sugar-producing and energy crop worldwide. The sugar beet pure line IMA1 independently bred by Chinese scientists is a standard diploid parent material that is widely used in hybrid-breeding programs. In this study, a high-quality, chromosome-level genome assembly for IMA1was conducted, and 99.1% of genome sequences were assigned to nine chromosomes. A total of 35,003 protein-coding genes were annotated, with 91.56% functionally annotated by public databases. Compared with previously released sugar beet assemblies, the new genome was larger with at least 1.6 times larger N50 size, thereby substantially improving the completeness and continuity of the sugar beet genome. A Genome-Wide Association Studies analysis identified 10 disease-resistance genes associated with three important beet diseases and five genes associated with sugar yield per hectare, which could be key targets to improve sugar productivity. Nine highly expressed genes associated with pollen fertility of sugar beet were also identified. The results of this study provide valuable information to identify and dissect functional genes affecting sugar beet agronomic traits, which can increase sugar beet production and help screen for excellent sugar beet breeding materials. In addition, information is provided that can precisely incorporate biotechnology tools into breeding efforts.

Mechanically Efficient Cellular Materials Inspired by Cuttlebone.

Cellular materials with excellent mechanical efficiency are essential for aerospace structures, lightweight vehicles, and energy absorption. However, current synthetic cellular materials, such as lattice materials with a unit cell arranged in an ordered hierarchy, are still far behind many biological cellular materials in terms of both structural complexity and mechanical performance. Here, the complex porous structure and the mechanics of the cuttlebone are studied, which acts as a rigid buoyancy tank for cuttlefish to resist large hydrostatic pressure in the deep-sea environment. The cuttlebone structure, constructed like lamellar septa, separated by asymmetric, distorted S-shaped walls, exhibits superior strength and energy-absorption capability to the octet-truss lattice and conventional polymer and metal foams. Inspired by these findings, mechanically efficient cellular materials are designed and fabricated by 3D printing, which are greatly demanded for many applications including aerospace structures and tissue-engineering-scaffold. This study represents an effective approach for the design and engineering of high-performance cellular materials through bioinspired 3D printing.

The Efficacy of Interlimb-Coordinated Intervention on Gait and Motor Function Recovery in Patients with Acute Stroke: A Multi-Center Randomized Controlled Trial Study Protocol.

BACKGROUND: The efficacy of interlimb-coordinated training on gait and upper limb functional improvement remains unclear. The latest published randomized controlled trials have supported the potential benefits of interlimb-coordinated training to enhance gait function. Upper limb functional recovery may also benefit from interlimb-coordinated training since most everyday activities require the coordinated use of both hands to complete a task. This study investigates the efficacy of interlimb-coordinated training on gait and upper limb functional recovery over a short-medium term period. METHODS: A total of 226 acute stroke patients will be recruited from four centres over four years. Patients will be randomly allocated to either conventional therapy or conventional therapy plus interlimb-coordinated training. Outcomes will be recorded at baseline, after 2 weeks of intervention, and at 3- and 6-months post-intervention. Gait speed is the primary outcome measure. Secondary outcome measures include Fugl-Meyer Assessment of Motor Recovery, Berg Balance Scale, Timed Up and Go test, Action Research Arm Test, electroencephalography, and magnetic resonance imaging. CONCLUSION: The results of this trial will provide an in-depth understanding of the efficacy of early interlimb-coordinated intervention on gait and upper functional rehabilitation and how it may relate to the neural plasticity process.

[Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions and activities of matrix metalloproteinases in human skin fibroblasts and human leukemia cell line THP-1].

OBJECTIVE: In order to reveal the treatment mechanism of Chinese medicine with the effect of activating blood and resolving putridity, we selected acetyl-11-keto-beta-boswellic acid (AKBA) and arsenic trioxide (ATO), the main monomeric components of frankincense and arsenolite which are two most commonly used Chinese medicine with effect of activating blood and resolving putridity. We combined AKBA and ATO as a compound, and explored its regulatory role in productions and activities of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 in human skin fibroblasts (HSFbs) and human acute monocytic leukemia cell line THP-1 in inflammatory state. METHODS: In order to simulate the inflammatory micro-environment of chronic wounds, we established 3 cell models: HSFb model activated by tumor necrosis factor-alpha (TNF-α), THP-1 cell model activated by phorbol-12-myristate-13-acetate (PMA) and HSFb-THP-1 cell coculture system. AKBA and ATO were cocultured with these cell models. Enzyme-linked immunosorbent assay (ELISA), gelatin zymography assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to test the secretions, activities and mRNA expressions of MMP-1, MMP-2 and MMP-9. In the study of the regulatory mechanism of AKBA and ATO on MMPs, AKBA and ATO were cocultured with the cell models. ELISA was used to test the secretions of TNF-α and interleukin-1beta (IL-ß) and Western blot was used to test the phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated proteinkinase (p38MAPK). RESULTS: Compound of AKBA and ATO inhibited MMP-1, MMP-2 and MMP-9 mRNA expressions, secretions and activities respectively in HSFbs and THP-1 cells in inflammatory state (P<0.05, P<0.01). Also compound of AKBA and ATO inhibited secretions of TNF-α and IL-1ß in THP-1 cells and cell coculture system (P<0.01). It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFbs and THP-1 cells (P<0.05, P<0.01). CONCLUSION: The combined use of AKBA and ATO which in line with the rule of activating blood and resolving putridity inhibits fibroblasts and inflammatory cells in producing MMPs in inflammatory state through inhibiting the release of inflammatory factors and MAPK cascade pathway.

Salvianolic acid B in vitro inhibited matrix metalloproteinases-1, -2, and -9 activities.

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all extracellular matrix components. The proteolytic property of the MMPs is important during wound healing to remove debris and facilitate cell migration. Targeting towards the decreased MMPs activities is a new treatment strategy for healing chronic wounds. Salvia miltiorrhiza is a popular Chinese herb that could promote chronic ulcers healing for topical use. Salvianolic acid B (Sal B) is the most abundant bioactive component in Salvia miltiorrhiza. The research was designed to explore the inhibitory effects of Sal B on MMP-1, MMP-2 and MMP-9 activities. METHODS: Pure human interstitial collagenase (MMP-1) or gelatinase A (MMP-2) was activated by p-aminophenylmercuric acetate (APMA), and was incubated with Sal B for 1 h. The activities were observed by quenched fluorescent substrate. Gelatinase B (MMP-9) is rich in polymorphonuclear neutrophils (PMN), so the rat PMN was used as a source of MMP-9 for MMPs activity assays. In vitro MMP-9 from rats' PMN lysate was incubated with Sal B for 1 h, and its activity was tested by gelatin zymography. RESULTS: Sal B dose-dependently inhibited the human MMP-1 and MMP-2 activities in the range of 0.002 4 to 0.3 g/L, with 50% inhibiting concentration (IC(50)) of (0.090<0.015) g/L and (0.080<0.005) g/L respectively. In the range of 0.003 to 0.3 g/L, Sal B could inhibit the MMP-9 activity (P<0.01). CONCLUSION: The broad-spectrum inhibitory effects of Sal B on MMPs may reveal one of the mechanisms for the effects of Salvia miltiorrhiza on chronic wounds.

Arsenic trioxide regulates the production and activities of matrix metalloproteinases-1, -2, and -9 in fibroblasts and THP-1.

BACKGROUND: The elevated matrix metalloproteinase (MMP) activity is an important cause of chronic wound healing failure. Arsenolite, whose main component is arsenic trioxide (As2O3), is a common traditional Chinese medicine wildly used in treating chronic wounds; it can remove necrotic tissue and promote tissue regeneration. This research was designed to evaluate the effects of As2O3 on production and activities of MMP-1, MMP-2 and MMP-9, and on regulation of its signal transduction pathway in human skin fibroblasts (HSFb) and human monocyte line (THP-1 cells) that were in an inflammatory state. METHODS: We established three cell models; HSFb activated by TNF-α, THP-1 cells activated by phorbol 12-myristate 13-acetate (PMA) and an HSFb-THP-1 co-culture system. Three cell models was cultured with As2O3 for 24 hours. The levels of MMP-1, MMP-2, MMP-9, TNF-α and IL-1ß in the cell culture supernatants were assayed by ELISA. The mRNA expressions of MMP-1, MMP-2 and MMP-9 were determined by RT-PCR. The activities of MMP-2 and MMP-9 were tested by Gelatin zymography assays. The phosphorylation levels of ERK1/2 and p38MAPK were assayed by Western blotting. RESULTS: As2O3 inhibited the expression of MMP-1, MMP-2 and MMP-9 mRNA, the secretion and activity of MMP-1, MMP-2 and MMP-9 in HSFb and THP-1 cells in the inflammatory state (P < 0.05 and P < 0.01 respectively). It also inhibited the secretion of TNF-α and IL-1ß in THP-1 cells and in the co-culture system (P < 0.05 and P < 0.01, respectively). It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFb and THP-1 cells (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: As2O3, as a main component of arsenolite, can inhibit the production of MMPs by HSFb and THP-1 cells in an inflammatory state through inhibiting the release of inflammatory factors and the activation of the MAPK cascade pathway. This may be a possible mechanism for arsenolite healing chronic wounds.