A Network Meta-analysis to Explore the Effectiveness of the Different Treatment Modalities in Acne Scars.

BACKGROUND: Multiple treatments are used to treat acne scars, but comparing the effectiveness of these treatments have not been studied yet. This research aimed to conduct a complete analysis of the effectiveness of commonly used therapies in acne scars. METHODS: PubMed, Embase, and Cochrane's Library (Cochrane Center Register of Controlled Trials) databases were searched through May 2023. We used patient satisfaction score as the primary outcome and Goodman Baron qualitative scar grading system as the secondary outcome to evaluate the effectiveness of different commonly used therapies for acne scarring, including laser, microneedling (MN), platelet-rich plasma (PRP), autologous fat grafting and combined therapies. RESULTS: Herein, 495 patients from 13 studies were included. Our results showed that PRP combined with laser was the most effective among therapies in treating acne scars. Ranking of effectiveness by the surface under the cumulative ranking (SUCRA) curve for patient satisfaction score was as following: PRP + laser (96.2%) > laser (71.2%) > MN (45.5%) > MN + PRP (42.0%) > autologous fat grafting (24.5%) > PRP (20.5%). Additionally, ranking of effectiveness by the SUCRA curve for Goodman Baron qualitative scar grading system was as following: PRP + laser (86.3%) > laser (64.2%) > MN + PRP (54.2%) > MN (37.2%) > PRP (8.1%). CONCLUSION: This network meta-analysis indicated that the combined therapy of PRP and laser might be the most effective. Additionally, more high-quality randomized controlled trials are needed to verify our findings. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Establishment of a Homologous Silencing System with Intact-Plant Infiltration and Minimized Operation for Studying Gene Function in Herbaceous Peonies.

Gene function verification is a crucial step in studying the molecular mechanisms regulating various plant life activities. However, a stable and efficient homologous genetic transgenic system for herbaceous peonies has not been established. In this study, using virus-induced gene silencing technology (VIGS), a highly efficient homologous transient verification system with distinctive advantages was proposed, which not only achieves true "intact-plant" infiltration but also minimizes the operation. One-year-old roots of the representative species, Paeonia lactiflora Pall., were used as the materials; prechilling (4 °C) treatment for 3-5 weeks was applied as a critical precondition for P. lactiflora to acquire a certain chilling accumulation. A dormancy-related gene named HOMEOBOX PROTEIN 31 (PlHB31), believed to negatively regulate bud endodormancy release (BER), was chosen as the target gene in this study. GFP fluorescence was detected in directly infiltrated and newly developed roots and buds; the transgenic plantlets exhibited remarkably earlier budbreak, and PlHB31 was significantly downregulated in silenced plantlets. This study established a homologous transient silencing system featuring intact-plant infiltration and minimized manipulation for gene function research, and also offers technical support and serves as a theoretical basis for gene function discovery in numerous other geophytes.

Electric field promotes dermal fibroblast transdifferentiation through activation of RhoA/ROCK1 pathway.

With the increased incidence of age-related and lifestyle-related diseases, chronic wounds are sweeping the world, where recent studies reveal that dysfunction of fibroblast plays an indispensable role. Endogenous electric field (EF) generated by skin wound disrupting an epithelial layer has been used as an alternative clinical treatment in chronic wound by modulating cellular behaviours, including fibroblasts transdifferentiation. Although many molecules and signaling pathways have been reported associated with fibroblasts transdifferentiation, studies investigating how the electric field affects the cellular pathways have been limited. For this purpose, a model of electric field treatment in vitro was established, where cells were randomly divided into control and electrified groups. The changes of protein expression and distribution were detected under different conditions, along with Zeiss imaging system observing the response of cells. Results showed that fibroblast transdifferentiation was accompanied by increased expression of a-SMA and extracellular matrix (COL-1 and COL-3) under the EF. Simultaneously, fibroblast transdifferentiation was also consistent with changes of cell arrangement and enhanced motility. Furthermore, we found that electric field activated RhoA signaling pathways activity. Y-27632, a RhoA inhibitor, which was used to treat fibroblasts, resulted in reduced transdifferentiation. The connection between electric field and RhoA signaling pathways is likely to be significant in modulating fibroblast transdifferentiation in acute injury and tissue remodeling, which provides an innovative idea for the molecular mechanism of EF in promoting chronic wound healing.

From clicks to change: The role of Internet use in fostering environmental sustainability awareness.

The purpose of this paper is to explore how Internet use affects an individual's environmental sustainability awareness. To this end, we adopt data from the 2021 wave of Chinese General Social Survey, measure the environmental sustainability awareness by 14 categories of items, and employ a treatment effect model to identify the relationship. The results reveal that Internet use is significantly associated with an increase in people's environmental sustainability awareness. Our study sheds light on the underlying mechanism of the positive correlation via an information-based channel. Furthermore, we also find that the facilitating effect is more pronounced in economically developed regions. This work provides a new insight into the determinants of environmental sustainability awareness and offers several implications to conduct sustainable development policies in the digital era.

MADS-box transcription factors determine the duration of temporary winter dormancy in closely related evergreen and deciduous Iris spp.

Winter dormancy (WD) is a crucial strategy for plants coping with potentially deadly environments. In recent decades, this process has been extensively studied in economically important perennial eudicots due to changing climate. However, in evergreen monocots with no chilling requirements, dormancy processes are so far a mystery. In this study, we compared the WD process in closely related evergreen (Iris japonica) and deciduous (I. tectorum) iris species across crucial developmental time points. Both iris species exhibit a 'temporary' WD process with distinct durations, and could easily resume growth under warm conditions. To decipher transcriptional changes, full-length sequencing for evergreen iris and short read RNA sequencing for deciduous iris were applied to generate respective reference transcriptomes. Combining results from a multipronged approach, SHORT VEGETATIVE PHASE and FRUITFULL (FUL) from MADS-box was associated with a dormancy- and a growth-related module, respectively. They were co-expressed with genes involved in phytohormone signaling, carbohydrate metabolism, and environmental adaptation. Also, gene expression patterns and physiological changes in the above pathways highlighted potential abscisic acid and jasmonic acid antagonism in coordinating growth and stress responses, whereas differences in carbohydrate metabolism and reactive oxygen species scavenging might lead to species-specific WD durations. Moreover, a detailed analysis of MIKCCMADS-box in irises revealed common features described in eudicots as well as possible new roles for monocots during temporary WD, such as FLOWERING LOCUS C and FUL. In essence, our results not only provide a portrait of temporary WD in perennial monocots but also offer new insights into the regulatory mechanism underlying WD in plants.

Later Growth Cessation and Increased Freezing Tolerance Potentially Result in Later Dormancy in Evergreen Iris Compared with Deciduous Iris.

Winter dormancy is a protective survival strategy for plants to resist harsh natural environments. In the context of global warming, the progression of dormancy has been significantly affected in perennials, which requires further research. Here, a systematic study was performed to compare the induction of dormancy in two closely related iris species with an ecodormancy-only process, the evergreen Iris japonica Thunb. and the deciduous Iris tectorum Maxim. under artificial conditions. Firstly, morphological and physiological observations were evaluated to ensure the developmental status of the two iris species. Furthermore, the expression patterns of the genes involved in key pathways related to plant winter dormancy were determined, and correlation analyses with dormancy marker genes were conducted. We found that deciduous iris entered dormancy earlier than evergreen iris under artificial dormancy induction conditions. Phytohormones and carbohydrates play roles in coordinating growth and stress responses during dormancy induction in both iris species. Moreover, dormancy-related MADS-box genes and SnRKs (Snf1-related protein kinase) might represent a bridge between carbohydrate and phytohormone interaction during iris dormancy. These findings provide a hypothetical model explaining the later dormancy in evergreen iris compared with deciduous iris under artificial dormancy induction conditions and reveal some candidate genes. The findings of this study could provide new insights into the research of dormancy in perennial plants with an ecodormancy-only process and contribute to effectively managing iris production, postharvest storage, and shipping.

Development of a Multi-Criteria Decision-Making Approach for Evaluating the Comprehensive Application of Herbaceous Peony at Low Latitudes.

The growing region of herbaceous peony (Paeonia lactiflora) has been severely constrained due to the intensification of global warming and extreme weather events, especially at low latitudes. Assessing and selecting stress-tolerant and high-quality peony germplasm is essential for maintaining the normal growth and application of peonies under adverse conditions. This study proposed a modified multi-criteria decision-making (MCDM) model for assessing peonies adapted to low-latitude climates based on our previous study. This model is low-cost, timesaving and suitable for screening the adapted peony germplasm under hot and humid climates. The evaluation was conducted through the analytic hierarchy process (AHP), three major criteria, including adaptability-related, ornamental feature-related and growth habits-related criteria, and eighteen sub-criteria were proposed and constructed in this study. The model was validated on fifteen herbaceous peonies cultivars from different latitudes. The results showed that 'Meiju', 'Hang Baishao', 'Hongpan Tuojin' and 'Bo Baishao' were assessed as Level I, which have strong growth adaptability and high ornamental values, and were recommended for promotion and application at low latitudes. The reliability and stability of the MCDM model were further confirmed by measuring the chlorophyll fluorescence of the selected adaptive cultivars 'Meiju' and 'Hang Baishao' and one maladaptive cultivar 'Zhuguang'. This study could provide a reference for the introduction, breeding and application of perennials under everchanging unfavorable climatic conditions.

Cytotoxic steroidal glycosides from the underground parts of Hosta ventricosa.

A phytochemical study on the underground parts of Hosta ventricosa yielded one new spirostanol saponin (1), two new furostanol saponins (2 and 3), and one new pregnane glycoside (4), along with three known compounds (5‒7). Their structures were elucidated on the basis of chemical and spectroscopic analysis. All isolated compounds were evaluated for their cytotoxic effects against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW-480). Compounds 1, 2, and 5‒7 showed cytotoxic activities with IC50 values of 3.21-17.06 µM.

Chilling Requirement Validation and Physiological and Molecular Responses of the Bud Endodormancy Release in Paeonia lactiflora 'Meiju'.

The introduction of herbaceous peony (Paeonia lactiflora Pall.) in low-latitude areas is of great significance to expand the landscape application of this world-famous ornamental. With the hazards of climate warming, warm winters occurs frequently, which makes many excellent northern herbaceous peony cultivars unable to meet their chilling requirements (CR) and leads to their poor growth and flowering in southern China. Exploring the endodormancy release mechanism of underground buds is crucial for improving low-CR cultivar screening and breeding. A systematic study was conducted on P. lactiflora 'Meiju', a screened cultivar with a typical low-CR trait introduced from northern China, at the morphological, physiological and molecular levels. The CR value of 'Meiju' was further verified as 677.5 CUs based on the UT model and morphological observation. As a kind of signal transducer, reactive oxygen species (ROS) released a signal to enter dormancy, which led to corresponding changes in carbohydrate and hormone metabolism in buds, thus promoting underground buds to acquire strong cold resistance and enter endodormancy. The expression of important genes related to ABA metabolism, such as NCED3, PP2C, CBF4 and ABF2, reached peaks at the critical stage of endodormancy release (9 January) and then decreased rapidly; the expression of the GA2ox8 gene related to GA synthesis increased significantly in the early stage of endodormancy release and decreased rapidly after the release of ecodormancy (23 January). Cytological observation showed that the period when the sugar and starch contents decreased and the ABA/GA ratio decreased was when 'Meiju' bud endodormancy was released. This study reveals the endodormancy regulation mechanism of 'Meiju' buds with the low-CR trait, which lays a theoretical foundation for breeding new herbaceous peony cultivars with the low-CR trait.

Onion extract gel is not better than other topical treatments in scar management: A meta-analysis from randomised controlled trails.

To evaluate the efficacy and safety of onion extract (OE) gel on scar management, a systematic review was performed by searching Embase, PubMed, Medline, and the Cochrane Library databases, and a meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. Finally, 13 randomised controlled trails were enrolled for meta-analysis. OE gel increased the total improvement scores assessed by investigators (P < .00001) and patients (P < .00001) than no treatment, but no differences were detected between OE gel and other commonly used topical treatments assessed by investigators (P = .56) and patients (P = .39). Moreover, OE in silicone gel increased the total improvement scores assessed by investigators (P < .00001) and patients (P = .0007) than other treatments. OE gel increased the incidence of total adverse effects compared with no treatment (P < .0001) and other treatments (P = .008) by a fixed-effects model, and increased the incidence of dropping out caused by intolerance of treatments (P = .0002). OE gel not only has no superiority to commonly used topical treatments, but also has the potential to increase the incidence of adverse effects on scar management; OE in silicone gel might be the optimal topical choice for scar treatment; however, more evidences are needed to strength these conclusions.

Polarization of ADAM17-driven EGFR signalling in electric field-guided collective migration of epidermal sheets.

Endogenous electric field is considered to play an important role in promoting collective migration of epidermis to the wound centre. However, most studies are focused on the effect of bioelectric field on the movement and migration of single epithelial cell; the molecular mechanisms about collective migration of epidermal monolayers remain unclear. Here, we found that EFs dramatically promoted the collective migration of HaCaT cells towards the anode, activated the sheddase activity of ADAM17 and increased the phosphorylation level of EGFR. Moreover, EGFR phosphorylation and HB-EGF shedding level were significantly decreased by the ADAM17 inhibitor TAPI-2 or siADAM17 under EFs, which subsequently attenuated the directed migration of HaCaT sheets. Notably, the inhibition of EF-regulated collective migration by siADAM17 was rescued by addition of recombinant HB-EGF. Furthermore, we observed that F-actin was dynamically polarized along the leading edge of the migrated sheets under EFs and that this polarization was regulated by ADAM17/HB-EGF/EGFR signalling. In conclusion, our study indicated that ADAM17 contributed to the collective directional movement of the epidermal monolayer by driving HB-EGF release and activating EGFR under EFs, and this pathway also mediated the polarization of F-actin in migrating sheets, which is essential in directional migration.

Electric field down-regulates CD9 to promote keratinocytes migration through AMPK pathway.

Endogenous electric field (EF)-directed keratinocytes migration is known to play a key role in the wound re-epithelialization process. Although many molecules and signaling pathways are reported important for directional keratinocytes migration under EF, the underlying mechanism remains unclear. Our previous research found that CD9, a trans-membrane protein, is involved in wound re-epithelialization and CD9 downregulation contributes to keratinocytes migration. In this study, we observed the effect of EF on CD9 expression and keratinocytes migration. The keratinocytes migrated directionally toward the cathode and CD9 expression was down-regulated under EF (200mV/mm). In addition, CD9 overexpression reversed EF-induced migratory speed and the electrotactic response of keratinocytes. Also, we found that EF reduced AMP-activated protein kinase (AMPK) activity. Furthermore, AICAR, an AMPK activator, increased CD9 expression under EF, while compound C, an AMPK inhibitor, decreased CD9 expression in keratinocytes. Our results demonstrate that EF regulates CD9 expression and keratinocytes directional migration, in which AMPK pathway plays an important role.

The Efficacy and Safety of Finasteride Combined with Topical Minoxidil for Androgenetic Alopecia: A Systematic Review and Meta-analysis.

BACKGROUND: The combination of finasteride and topical minoxidil has been used for treating patients with androgenetic alopecia (AGA). However, whether combining these two medications results in greater efficacy than monotherapy is a question worth exploring. OBJECTIVE: This meta-analysis aims to determine the efficacy and safety of combined treatment of finasteride and topical minoxidil. METHODS: A comprehensive search of the Embase, PubMed, and the Cochrane Library databases was performed. Data were extracted and analyzed according to predefined clinical endpoints. RESULTS: Five randomized controlled trials (RCTs) were included in our meta-analysis. All studies compared combined therapy with minoxidil, but only 2 RCTs compared combined therapy with finasteride. Compared with minoxidil or finasteride alone, the combined group had a significantly higher global photographic evaluation score (P < 0.00001), more patients with marked improvement (P < 0.001), and fewer patients with deterioration or no change (P < 0.001). There was no significant difference between the combined group and minoxidil- or finasteride-only groups in the number of patients with moderate and mild improvements, hair density change, or adverse events. CONCLUSIONS: In patients with AGA, the combination treatment of finasteride and topical minoxidil has better therapeutic efficacy than and similar safety as monotherapy. However, the best concentration of combination treatment requires further studies with sound methodological quality. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Genome-Wide Association Studies and Transcriptome Changes during Acclimation and Deacclimation in Divergent Brassica napus Varieties.

Information concerning genes and signals regulating cold acclimation processes in plants is abundant; however, less is known about genes and signals regulating the deacclimation process. A population of primarily winter B. napus varieties was used to conduct a genome-wide association study and to compare the transcriptomes from two winter B. napus varieties showing time-dependent differences in response to cold acclimation and deacclimation treatments. These studies helped to identify loci, candidate genes, and signaling processes impacting deacclimation in B. napus. GWAS identified polymorphisms at five different loci associated with freezing tolerance following deacclimation. Local linkage decay rates near these polymorphisms identified 38 possible candidate genes. Several of these genes have been reported as differentially regulated by cold stress in arabidopsis (Arabidopsis thaliana), including a calcium-binding EF-hand family protein (encoded by BnaCnng10250D) that was also differentially expressed during deacclimation in this study. Thousands of other genes differentially expressed during the acclimation and deacclimation treatments implicated processes involving oxidative stress, photosynthesis, light-regulated diurnal responses, and growth regulation. Generally, responses observed during acclimation were reversed within one week of deacclimation. The primary differences between the two winter B. napus varieties with differential deacclimation responses involved protection from oxidative stress and the ability to maintain photosynthesis.

A novel FPCL model producing directional contraction through induction of fibroblast alignment by biphasic pulse direct current electric field.

Although parallel alignment of fibroblasts to the tension lines of scar has been evidenced in vivo, how scar contracture generates directional contraction remains largely unclear due to the lack of effective in vitro model. Fibroblast populated collagen lattice (FPCL), a widely used in vitro model, fails to mimic scar contracture since it produces concentric contraction with the random orientation of fibroblast. We hypothesized that a novel FPCL model with fibroblast alignment might produce directional contraction and then simulate scar contracture better. Here, we showed that although direct current electric fields (DCEFs) enabled fibroblasts aligned perpendicularly to the field vector, it also promoted electrotactic migration of fibroblast in FPCL. By contrast, biphasic pulse direct current electric fields (BPDCEFs), featured by reversal of the EF direction periodically, abolished the electrotactic migration, but induced fibroblast alignment in a pulse frequency dependent manner. Specifically, BPDCEF at a pulse frequency of 0.0002 Hz induced fibroblast alignment comparable to that induced by DCEF under the same field strength (300 mV/mm), leading to an enhanced contraction of FPCL along the direction of cell alignment. FPCL pretreated by BPDCEF showed an elliptical contraction whereas it was concentric in control FPCL. Further study revealed that F-actin redistributions acted as a key mechanism for the induction of fibroblasts alignment by BPDCEF. Cytochalasin D, an inhibitor of actin dynamics, abolished F-actins redistribution, and significantly suppressed the fibroblasts alignment and the directional contraction of FPCL. Importantly, BPDCEF significantly increased RhoA activity in fibroblasts, while this response was attenuated by C3 transferase pre-treatment, a potent inhibitor of RhoA, caused F-actin depolymerization and actin filament bundle randomly distributed. Taken together, our study suggests a crucial role for fibroblast orientation in scar contracture, and provides a novel FPCL model that may be feasible and effective for investigating scar contracture in vitro.

Mining and expression analysis of candidate genes involved in regulating the chilling requirement fulfillment of Paeonia lactiflora 'Hang Baishao'.

BACKGROUND: The artificial enlargement of the planting area and ecological amplitude of ornamentals for horticultural and landscape applications are significant. Herbaceous peony (Paeonia lactiflora Pall.) is a world-famous ornamental with attractive and fragrant flowers and is mainly planted in temperate and cool areas. Comparatively higher winter temperatures in the subtropical and tropical Northern Hemisphere result in a deficit of chilling accumulation for bud dormancy release, which severely hinders "The southward plantation of herbaceous peony". Studies on the dormancy, chilling requirement (CR) and relevant molecular mechanisms of peony are needed to enhance our ability to extend the range of this valuable horticultural species. RESULTS: Based on natural and artificial chilling experiments, and chilling hour (CH) and chilling unit (CU) evaluation systems, the lowest CR of 'Hang Baishao' was between 504.00 and 672.00 CHs and the optimal CR was 672.00 CHs and 856.08 CUs for achieving strong sprouting, growth and flowering performance. Transcriptome sequencing and gene identification by RNA-Seq were performed on 'Hang Baishao' buds during the dormancy and sprouting periods. Six gene libraries were constructed, and 66 temperature- and photoperiod-associated unigenes were identified as the potential candidate genes that may regulate or possibly determine CR characteristics. The difference in the expression patterns of SUPPRESSPOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) between the winters of 2012-2013 and 2015-2016, and the difference of CR fulfillment periods also between these two winters represented the interesting congruent relationships. This correlation was also observed for WRKY DNA-BINDING PROTEIN 33 (WRKY 33). CONCLUSIONS: Combined with the results acquired from all of experiments, 'Hang Baishao' was confirmed to be a superb peony resource that have significantly low CR characteristics. The two genes of SOC1 and WRKY33 are likely involved in determining the CR amount and fulfillment period of 'Hang Baishao'. HEAT SHOCK PROTEIN, OSMOTIN and TIMING OF CAB EXPRESSION 1 also deserve attention for the CR research. This study could contribute to the knowledge of the deep factors and mechanisms that regulate CR characteristics, and may be beneficial for breeding new germplasms that have low CRs for landscape or horticulture applications in subtropical regions.

BNIP3 promotes the motility and migration of keratinocyte under hypoxia.

The migration of keratinocytes from wound margins plays a critical role in the re-epithelialization of skin wounds. Hypoxia occurs immediately after injury and acts as an early stimulus to initiate the healing processes. Although our previous studies have revealed that hypoxia promotes keratinocyte migration, the precise mechanisms involved remain unclear. Here, we found that BNIP3 expression was upregulated in hypoxic keratinocytes, and BNIP3 silencing suppressed hypoxia-induced cell migration. Additionally, hypoxia activated the focal adhesion kinase (FAK) pathway through upregulation of BNIP3, while FAK inhibition attenuated hypoxic keratinocyte migration. Here, we conclusively demonstrate a novel role for BNIP3 in hypoxia-induced keratinocyte migration. Furthermore, we provide a new perspective on the molecular mechanisms of wound healing and identify BNIP3 as a potential new molecular target for clinical treatments to enhance wound healing.

Wound management and outcome of 595 electrical burns in a major burn center.

BACKGROUND: Electrical burns are important causes of trauma worldwide. This study aims to analyze the clinical characteristics, wound management, and outcome of electric burns. METHODS: This retrospective study was performed at the Institute of Burn Research of the Third Military Medical University during 2013-2015. Data including the demographics, injury patterns, wound treatment, and outcomes were collected and analyzed. RESULTS: A total of 595 electrical burn patients (93.8% males) were included. The average age was 37.3 ± 14.6 y, and most patients (73.5%) were aged 19∼50 years. Most patients (67.2%) were injured in work-related circumstances. The mean total body surface area was 8.8 ± 11.8% and most wounds (63.5%) were full-thickness burns. Operation times of high-voltage burns and current burns were higher than those of low-voltage burns and arc burns, respectively. Of the 375 operated patients, 83.2% (n = 312) underwent skin autografting and 49.3% (n = 185) required skin flap coverage. Common types of skin flaps were adjacent (50.3%), random (42.2%), and pedicle (35.7%). Amputation was performed in 107 cases (18.0%) and concentrated on the hands (43.9%) and upper limbs (39.3%). The mean length of stay was 42.9 ± 46.3 d and only one death occurred (0.2%). Current burns and higher numbers of operations were major risk factors for amputation and length of stay, respectively. CONCLUSIONS: Electrical burns mainly affected adult males with occupational exposures in China. Skin autografts and various skin flaps were commonly used for electric burn wound management. More standardized and effective strategies of treatment and prevention are still needed to decrease amputation rates.

HSP27 phosphorylation protects against endothelial barrier dysfunction under burn serum challenge.

F-actin rearrangement is an early event in burn-induced endothelial barrier dysfunction. HSP27, a target of p38 MAPK/MK2 pathway, plays an important role in actin dynamics through phosphorylation. The question of whether HSP27 participates in burn-related endothelial barrier dysfunction has not been identified yet. Here, we showed that burn serum induced a temporal appearance of central F-actin stress fibers followed by a formation of irregular dense peripheral F-actin in pulmonary endothelial monolayer, concomitant with a transient increase of HSP27 phosphorylation that conflicted with the persistent activation of p38 MAPK/MK2 unexpectedly. The appearance of F-actin stress fibers and transient increase of HSP27 phosphorylation occurred prior to the burn serum-induced endothelial hyperpermeability. Overexpressing phospho-mimicking HSP27 (HSP27(Asp)) reversed the burn serum-induced peripheral F-actin rearrangement with the augmentation of central F-actin stress fibers, and more importantly, attenuated the burn serum-induced endothelial hyperpermeability; such effects were not observed by HSP27(Ala), a non-phosphorylated mutant of HSP27. HSP27(Asp) overexpression also rendered the monolayer more resistant to barrier disruption caused by Cytochalasin D, a chemical reagent that depolymerizes F-actin specifically. Further study showed that phosphatases and sumoylation-inhibited MK2 activity contributed to the blunting of HSP27 phosphorylation during the burn serum-induced endothelial hyperpermeability. Our study identifies HSP27 phosphorylation as a protective response against burn serum-induced endothelial barrier dysfunction, and suggests that targeting HSP27 wound be a promising therapeutic strategy in ameliorating burn-induced lung edema and shock development.

NLRP3/1-mediated pyroptosis: beneficial clues for the development of novel therapies for Alzheimer's disease.

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis, which is a lytic, inflammatory form of cell death. There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer's disease. In this review, we summarize the possible pathogenic mechanisms of Alzheimer's disease, focusing on neuroinflammation. We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer's disease. Finally, we examine the neuroprotective activity of small-molecule inhibitors, endogenous inhibitor proteins, microRNAs, and natural bioactive molecules that target NLRP3 and NLRP1, based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer's disease.