Identification and Expression Analyses of the Special 14-3-3 Gene Family in Papaya and its Involvement in Fruit Development, Ripening, and Abiotic Stress Responses.

Plant 14-3-3 proteins play key roles in regulating growth, development, and stress responses. However, little is known about this gene family in papaya (Carica papaya L.). We characterized eight 14-3-3 genes from the papaya genome and designed them as CpGRF1-8. Based on phylogenetic, conserved motif, and gene structure analyses, papaya CpGRFs were divided into ε and non-ε groups. Expression analysis showed differential and class-specific transcription patterns in different organs. Quantitative real-time polymerase chain reaction analysis showed that most CpGRFs had large changes in expression during fruit development and ripening. This indicated that the CpGRFs were involved in regulating fruit development and ripening. Significant expression changes occurred after cold, salt, and drought treatments in papaya seedlings, indicating that CpGRFs were also involved in signaling responses to abiotic stress. These results provide a transcription profile of 14-3-3 genes in organs, during fruit development and ripening and in response to stress. Some highly expressed, fruit-specific, and stress-responsive candidate CpGRFs will be identified for further genetic improvement of papayas.

Identification, Expression, and Interaction Network Analyses of the CDPK Gene Family Reveal Their Involvement in the Development, Ripening, and Abiotic Stress Response in Banana.

Calcium-dependent protein kinases (CDPKs) play vital roles in the regulation of plant growth, development, and tolerance to various abiotic stresses. However, little information is available for this gene family in banana. In this study, 44 CDPKs were identified in banana and were classified into four groups based on phylogenetic, gene structure, and conserved motif analyses. The majority of MaCDPKs generally exhibited similar expression patterns in the different tissues. Transcriptome analyses revealed that many CDPKs showed strong transcript accumulation at the early stages of fruit development and postharvest ripening in both varieties. Interaction network and co-expression analysis further identified some CDPKs-mediated network that was potentially active at the early stages of fruit development. Comparative expression analysis suggested that the high levels of CDPK expression in FJ might be related to its fast ripening characteristic. CDPK expression following the abiotic stress treatments indicated a significant transcriptional response to osmotic, cold, and salt treatment, as well as differential expression profiles, between BX and FJ. The findings of this study elucidate the transcriptional control of CDPKs in development, ripening, and the abiotic stress response in banana. Some tissue-specific, development/ripening-dependent, and abiotic stress-responsive candidate MaCDPK genes were identified for further genetic improvement of banana.

[Experience of diagnosis and treatment for 89 patients with Marjolin's ulcers in lower limbs].

OBJECTIVE: To summarize the clinical features of Marjolin's ulcers in lower limbs and the diagnosis and treatment methods for it.
 Methods: The clinical data of 89 patients with lower limbs Marjolin's ulcers, who were treated in Xiangya Hospital, Central South University from Jan 1998 to Dec 2017, were retrospectively analyzed, including demographics, injury factors, length of cancer incubation period, lesion location, ulcer area, pathological type, bone invasion, lymph node metastasis, surgical methods, repair methods and prognosis.
 Results: There were 70 males and 19 females among 89 patients with lower limbs Marjolin's ulcers. The most common injuries were flame burn (42 cases), trauma (19 cases), and burns (12 cases). The lesions were most common in the lower leg (31 cases), followed by the thigh (11 cases) and the heel (11 cases). The ulcer area was 1.5-600.0 cm2. There were 80 cases of squamous cell carcinoma, 8 cases of verrucous carcinoma, and 1 case of sarcoma. Before operation, 78 cases of inguinal lymphadenectasis were found, 49 cases of inguinal lymph node dissection, 29 cases of simple lymph node biopsy and resection, and 9 cases of lymph node metastasis and 8 cases of bone invasion were observed; 24 cases of amputation, 53 cases of extended resection and skin grafts, and 12 patients of extensive resection and flap transplantation were performed. Sixty-five cases were followed up, and 8 cases recurred, including 2 cases of amputation patients and 6 cases of extended resection patients. There was no relationship between recurrence of tumors and surgical methods (P>0.05).
 Conclusion: The recurrence and metastasis rate of Marjolin's ulcers in lower limbs is high, requiring early detection, early diagnosis, early surgical treatment and regular follow-up. Lnguinal lymphadenectasis is more common and requires lymph node biopsy and lymphadenectomy, or lymph node dissection. Extended local resection, skin graft or flap repair is the main treatment methods. However, amputation can be considered if the cancer is big, the invasion is deep, and the lower extremity scar is extensive and combined with severe deformity.

Role of XIST/miR-29a/LIN28A pathway in denatured dermis and human skin fibroblasts (HSFs) after thermal injury.

Denatured dermis is a part of the dermis in deep burn wound and has the ability to restore normal morphology and function. In our previous study, we revealed that miR-29a downregulation in denatured dermis may help burn wound healing in the later phase, and further enhance type I collagen synthesis. LIN28A, a highly-conserved RNA binding protein expressed during embryogenesis, plays roles in development, pluripotency, metabolism, as well as tissue repair in adults. In the present study, we investigated the functional roles of LIN28A in human skin fibroblasts (HSFs) and extracellular matrix (ECM), and the interaction between miR-29a and LIN28A. In recent years, long non-coding RNAs have been reported to play a key role in normal development and physiology, as well as in disease development. By using online tools, we screened out several candidate lncRNAs of miR-29a, among which XIST was inversely regulated by miR-29a. XIST, one of the first found cancer-associated lncRNAs, has been frequently reported to play major role in several biological processes. Further, we evaluated the roles and mechanism of XIST in HSF proliferation, migration, and ECM synthesis. Through regulation of miR-29a/LIN28A, XIST knockdown suppressed HSF proliferation, migration, and ECM synthesis. In denatured dermis tissues, XIST, and LIN28A expression was upregulated, miR-29a expression was downregulated. Taken together, promoting XIST expression in denatured dermis, thus to inhibit miR-29a and promote LIN28A expression, further promote HSF proliferation, migration, and ECM synthesis presents a promising strategy for denatured dermis repair.

Comprehensive Analysis of Long Noncoding RNAs and Messenger RNAs Expression Profiles in Patients with Marjolin Ulcer.

BACKGROUND Marjolin ulcer (MU) is an aggressive cutaneous malignancy. Typically, MU occurs over a period of time in post-burn and/or post-traumatic lesions and scars. However, the pathogenesis of scar carcinogenesis and MU development remains to be elucidated. The present study aimed to investigate the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiling in MU, which could provide new information on the potential molecular mechanisms of MU development. MATERIAL AND METHODS The lncRNA microarray analysis was conducted in normal skin, scar, and MU tissue, and quantitative real-time PCR experiment was carried out to validate the reliability of the microarray data. Furthermore, a series of integrative bioinformatic approaches were applied to decipher the function of differentially expressed lncRNAs. RESULTS A total of 7130 lncRNAs and 9867 mRNAs were differentially expressed among normal skin, scar, and MU tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that these aberrantly expressed transcripts were mainly involved in cell cycle, immune response, and the p53 signaling pathway. Series Test of Cluster analysis indicated certain dysregulated lncRNAs were expressed with a gradually increasing or decreasing trend and might participated in malignant transformation of scar tissue postburn. Co-expression analysis showed 5 selected lncRNAs might regulate cell proliferation through the p53 signaling pathway. Finally, the competing endogenous RNA (ceRNA) network indicated that lncRNA uc001oou.3 might be implicated in ceRNA mechanism during MU development. CONCLUSIONS Taken together, our study implied the aberrant expression of lncRNAs may play an important role in the pathogenesis and development of MU, and the exact mechanism warrants further investigation.

Myofibroblasts contribute to but are not necessary for wound contraction.

Wound contraction facilitates tissue repair. The correct balance between too little contraction, which leads to non-healing wounds, and too much contraction, which leads to contractures, is important for optimal healing. Thus, understanding which cells cause wound contraction is necessary to optimize repair. Wound contraction is hypothesized to develop from myofibroblast (cells which express alpha-smooth muscle actin; ACTA2) contractility, while the role of fibroblast contractility is unknown. In this study, we utilized ACTA2 null mice to determine what role fibroblasts play in wound contraction. Human scar contractures were immunostained for ACTA2, beta-cytoplasmic actin (ACTB), and gamma-cytoplasmic actin (ACTG1). Full-thickness cutaneous wounds were created on dorsum of ACTA2(+/+) mice and strain-matching ACTA2(+/-) and ACTA2(-/-) mice. Wound contraction was quantified. Tissue was harvested for histologic, immunohistochemical and protein analysis. Compared with surrounding unwounded skin, human scar tissue showed increased expression of ACTA2, ACTB, and ACTG1. ACTA2 was focally expressed in clusters. ACTB and ACTG1 were widely, highly expressed throughout scar tissue. Wound contraction was significantly retarded in ACTA2(-/-) mice, as compared to ACTA2(+/+) controls. Control mice had increased epithelialization, cell proliferation, and neovascularization. ACTA2(-/-) mice had lower levels of apoptosis, and fewer total numbers of cells. Smaller amount of collagen deposition and immature collagen organization in ACTA2(-/-) mice demonstrate that wounds were more immature. These data demonstrate that myofibroblasts contribute to but are not necessary for wound contraction. Mechanisms by which fibroblasts promote wound contraction may include activation of contractile signaling pathways, which promote interaction between non-muscle myosin II and ACTB and ACTG1.

CTCF and cohesin cooperatively mediate the cell-type specific interchromatin interaction between Bcl11b and Arhgap6 loci.

CCCTC-binding factor (CTCF) is a master organizer of genome spatial organization and plays an important role in mediating extensive chromatin interactions. Circular chromosome conformation capture (4C) is a high-throughput approach that allows genome-wide screening for unknown potential interaction partners. Using a conserved CTCF binding site on the Bcl11b locus as bait, an interaction partner at the Arhgap6 locus on a different chromosome was identified by 4C. Additional experiments verified that the interchromatin interaction between the Bcl11b and Arhgap6 loci was cell-type specific, which was cooperatively mediated by CTCF and cohesin. Functional analysis showed that the interchromatin interaction partners were repressing regulatory elements. These results indicate that interaction chromatin loops regulate the expression of the relevant genes.

Identification and expression analysis of four 14-3-3 genes during fruit ripening in banana (Musa acuminata L. AAA group, cv. Brazilian).

To investigate the regulation of 14-3-3 proteins in banana (Musa acuminata L. AAA group, cv. Brazilian) fruit postharvest ripening, four cDNAs encoding 14-3-3 proteins were isolated from banana and designated as Ma-14-3-3a, Ma-14-3-3c, Ma-14-3-3e, and Ma-14-3-3i, respectively. Amino acid sequence alignment showed that the four 14-3-3 proteins shared a highly conserved core structure and variable C-terminal as well as N-terminal regions with 14-3-3 proteins from other plant species. Phylogenetic analysis revealed that the four 14-3-3 genes belong to the non-ε groups. They were differentially and specifically expressed in various tissues. Real-time RT-PCR analysis indicated that these four genes function differentially during banana fruit postharvest ripening. Three genes, Ma-14-3-3a, Ma-14-3-3c, and Ma-14-3-3e, were significantly induced by exogenous ethylene treatment. However, gene function differed in naturally ripened fruits. Ethylene could induce Ma-14-3-3c expression during postharvest ripening, but expression patterns of Ma-14-3-3a and Ma-14-3-3e suggest that these two genes appear to be involved in regulating ethylene biosynthesis during fruit ripening. No obvious relationship emerged between Ma-14-3-3i expression in naturally ripened and 1-MCP (1-methylcyclopropene)-treated fruit groups during fruit ripening. These results indicate that the 14-3-3 proteins might be involved in various regulatory processes of banana fruit ripening. Further studies will mainly focus on revealing the detailed biological mechanisms of these four 14-3-3 genes in regulating banana fruit postharvest ripening.

Silicone ring implantation in an excisional murine wound model.

UNLABELLED: A good animal model for wound healing is indispensable for researchers to study the basic mechanism of tissue repair, and to develop strategies for clinical treatment. Small mammalian wound healing models are the most popular animal models for wound healing research because they are inexpensive, readily obtainable, and easy to handle. One significant challenge of using mice to evaluate wound repair is that wound contraction originates outside of tissue, whereas in humans, re-epithelialization and granulation tissue formation occurs within the wound space. METHODS: The present study describes a new excisional skin wound model utilizing an implanted silicone ring on the dorsal side of the mouse for 1 week prior to creating a fullthickness skin defect wound. RESULTS: The results showed that the time required for complete epithelialization of the wound was extended, the re epithelialization ratio was increased, and more granulation tissue was formed. CONCLUSION: Permitting the wound to heal mainly through re-epithelialization and granulation tissue formation, this new technique can result in a new excisional murine wound model that closer approximates human wound healing, allowing for more relevant evaluation of molecular signaling and cellular metabolism that occur during skin wound healing. .

Validation of a Novel Rodent Model to Test Anti-scarring Therapeutics.

UNLABELLED: Scar contracture is a debilitating disease that affects many people worldwide. There are currently no effective preventative medi- cal treatments. A pivotal step to attaining the goal of developing a treatment is the testing of anti-scarring agents in preclinical hierarchi- cal animal models of human scarring. METHODS: A 2-cm x 2-cm, full- thickness, excisional wound was created in the rats' mid-scapular area. Three experiments were performed. The first experiment determined the optimal dressing in wound contraction. The second experiment de- veloped upon the results of the first experiment, and determined how anatomic site of osmotic pump implantation affected wound healing. The third experiment determined how the size of osmotic pump affect- ed wound healing. Wound healing parameters including rate of wound contraction, systemic and local toxicity, proliferation, collagen archi- tecture, and collagen production were assessed. RESULTS: The results of the present study showed that covering the wound with TegadermTM (3M Health Care, St. Paul, MN) alone had the most linear wound con- traction rate with the smallest standard error of the mean. Implanta- tion of all osmotic pump sizes, when implanted intraperitoneally, was tolerated and did not interfere with wound healing. In contrast, sub- cutaneous implanted pumps caused significant discomfort in the rats. CONCLUSION: Implantation of an osmotic pump intraperitoneal in the rat excisional wound model, where the wound is covered with Tegaderm, provides for a reproducible, accurate, preclinical animal model to study anti-scar contracture treatments. .

Preliminary proteomic analysis of circulating polymorphonuclear neutrophils from rabbits experiencing scald injury and Staphylococcus aureus sepsis.

BACKGROUND: The aim of this study is to identify the differentially expressed proteins in circulating polymorphonuclear neutrophils (PMN) from scalded bacteremia rabbits infected with Staphylococcus aureus to provide a basis to reveal the pathogenesis of burns and sepsis. METHODS: Rabbits were subjected to sham burn (A), A + bacterial challenge (B), 30% scald injury (C), or C + bacterial challenge (D). Bacterial challenge was inflicted as an injection of 2.0 x 10(8) cfu S. aureus 18 h after burn procedure. Animals were sacrificed 24 h after burn. PMN were isolated, and the differential proteins in the PMN from these animals were identified by two-dimensional electrophoresis coupled with MALDI-TOF-MS; two proteins were confirmed by Western blotting. RESULTS: Twenty-one differential protein spots were found, and seven differential proteins were identified. Among the identified proteins, the expression levels of protein disulfide-isomerase and thiol-specific antioxidant protein were down-regulated in groups C and D, and two protein spots of annexin I were identified, one of which was down-regulated and another up-regulated in groups C and D. CONCLUSIONS: Preliminary proteome changes in PMN from rabbits experiencing scald injury and S. aureus sepsis were revealed, which possibly play an important role in the inflammation and pathogenesis of sepsis after scald injury.

Evolution of External Health Costs of Electricity Generation in the Baltic States.

Implementation of strict policies for mitigating climate change has a direct impact on public health as far as the external health costs of electricity generation can be reduced, thanks to the reduction of emission of typical pollutants by switching to cleaner low carbon fuels and achieving energy efficiency improvements. Renewables have lower external health costs due to the lower life cycle emission of typical air pollutants linked to electricity generation, such as SO2, NOx, particulate matter, NH3, or NMVOC (Non-methane volatile organic compounds), which all appear to have serious negative effects on human health. Our case study performed in the Baltic States analyzed the dynamics of external health costs in parallel with the dynamics of the main health indicators in these countries: life expectancy at birth, mortality rates, healthy life years, self-perceived health, and illness indicators. We employed the data for external health costs retrieved from the CASES database, as well as the health statistics data compiled from the EUROSTAT database. The time range of the study was 2010-2018 due to the availability of consistent health indicators for the EU Member States. Our results show that the decrease of external health costs had a positive impact on the increase of the self-perceived good health and reduction of long-standing illness as well as the decrease of infant death rate. Our conclusions might be useful for other countries as well as for understanding the additional benefits of climate change mitigation policies and tracking their positive health impacts. The cooperation initiatives on clean energy and climate change mitigation between countries like One Belt One Road initiative by the Chinese government can also yield additional benefits linked to the public health improvements.

linc00174-EZH2-ZNF24/Runx1-VEGFA Regulatory Mechanism Modulates Post-burn Wound Healing.

Preservation of denatured dermis exerts promotive functions in wound healing and improves the appearance and function of skin. Angiogenesis is crucial for wound healing during burn injury. However, the potential molecular mechanism of angiogenesis in the recovery after burn injury remains to be elucidated. Herein, RNA chromatin immunoprecipitation (ChIP) sequencing analysis revealed upregulation of long intergenic non-coding RNA 00174 (linc00174) in the post-burn tissues. linc00174 overexpression promoted angiogenic activities of human umbilical vein endothelial cells (HUVECs) in the heat-denatured cell model, characterized by the promotion of cell proliferation, migration, and tube formation. Mechanistically, linc00174 directly bound to enhancer of zeste homolog 2 (EZH2), thus stimulating the protein level of trimethylation at lysine 27 of histone H3 (H3K27me3). Moreover, inhibition of EZH2 resulted in downregulation of ZNF24 and Runx1, as well as a decline of vascular endothelial growth factor A (VEGFA). Furthermore, EZH2 modulated epigenetic repression of ZNF24 and Runx1 through the promoter of H3K27me3. Additionally, ZNF24 and Runx1 both functioned as transcriptional inhibitors of VEGFA. Taken together, these findings uncover that linc00174 epigenetically inhibits ZNF24 and Runx1 expression through binding to EZH2, thus attenuating the suppression of VEGFA, contributing to the facilitation of angiogenesis during the recovery of heat-denatured endothelial cells.

Epidemiology and outcome analysis of facial burns: A retrospective multicentre study 2011-2015.

BACKGROUND: The head and neck regions are frequent sites of burns, but few studies have analysed and reported the epidemiology of facial burns. As the face is the centre of one's identity and persona, facial injuries often result in physical and psychological morbidity. The aim of this article is to describe the epidemiology and outcome of facial burns in China and to suggest future preventive strategies. METHODS: This retrospective analysis included all patients with facial burns in a database at eight institutions from 2011-2015. The data collected included sex, age, month distribution, aetiology, location, presence of inhalation injury, total burn surface area, burn surface area with full-thickness and outcome including Post-traumatic stress disorder Checklist-Civilian Version scores and mortality. SPSS 19.0 software was used to analyse the data. RESULTS: A total of 1126 patients were included; 65.63% (739) had facial burns, of which 546 (73.88%) were male patients and 193 (26.12%) were female patients. Predictors of facial burns were being of male sex, working-related place, flame burns, total body surface area, and full-thickness burns. In addition, total body surface area and full-thickness burns increased the risk of poor prognosis for post-traumatic stress disorder and mortality. CONCLUSIONS: Facial burns benefit not only the healing of wound, but also the prevention of their incidence and PTSD symptom. This study may contribute to the elaboration of strategies to prevent facial burns and the establishment of a nationwide burn database in China.

Expression changes in protein-coding genes and long non-coding RNAs in denatured dermis following thermal injury.

OBJECTIVE: Thermal injury repair is a complex process during which maintaining the proliferation of human dermis fibroblasts (HDFs) and synthesis of extracellular matrix (ECM) plays a critical role. In the present study, we analyzed potential molecular markers and the probable association between differentially-expressed lncRNAs and protein-coding genes within denatured dermis following thermal injury, attempting to provide further insights to thermal injury repair pathogenesis. METHODS AND MAIN RESULTS: We found that the expression of 3940 lncRNAs was increased, while that of 1438 lncRNAs was reduced in the denatured dermis following thermal injury when compared to normal tissue. Of them, 338 were upregulated and 154 were downregulated by more than 128 times. Via cross-check with another microarray profile analysis on differentially-expressed lncRNAs after thermal injury, LINC00302 was found to be downregulated after thermal injury; more importantly, this skin-specially expressed lncRNA is located near a series of genes related to multiple skin inflammation and skin barrier-associated genomes. LINC00302 overexpression promoted the cell viability and the protein levels of α-SMA and Collagen I in HDFs. CONCLUSIONS: In conclusion, mRNAs and lncRNAs could be differentially expressed in the denatured dermis following thermal injury. mRNA and lncRNA regulatory signaling pathways could participate in thermal injury repair pathogenesis. More importantly, LINC00302 may play a critical role in thermal injury repair.

[Proteomic study of peripheral blood lymphocytes of rabbits with severe burn and Pseudomonas aeruginosa sepsis].

OBJECTIVE: To study the effect of severe burn and Pseudomonas aeruginosa sepsis on the proteomics of lymphocytes (LCs) of rabbits. METHODS: Twenty-four rabbits were divided into four groups, i.e. control, severe scald, severe scald and 2-hour sepsis, severe scald and 6-hour sepsis (6 rabbits in each group). The scald in rabbits was third degree in depth involving 30% of total body surface area (TBSA). The sepsis model was reproduced by intravenous injection of a suspension of Pseudomonas aeruginosa (ATCC 27853, 6 x 10(12)cfu/L) 1 ml/kg 24 hours after scald. The rabbits in control group were treated with warm water of 37 centigrade. Peripheral blood was obtained from the carotid artery 24 hours after scald, or 2 hours after sepsis, or 6 hours after sepsis. The LCs in each blood sample were separated, disrupted and the total proteins of LCs were extracted. The proteins were separated by two dimensional gel electrophoresis. The gels were stained with Coomassie brilliant blue and then were scanned. The images were analyzed by PD quest software. The protein spots of discrepant expression were sieved and then analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The peptide mass finger printing (PMFs) were obtained and were input into the data bank of proteins for identification of the proteins. RESULTS: The average spots of 6 gels were 1 051+/-21 (control), 1 026+/-30 (severe scald), 1 078+/- 36 (2-hour sepsis) and 1 065+/-31 (6-hour sepsis), and the average matching rate were 91% (control), 89% (severe scald), 92% (2-hour sepsis) and 94% (6-hour sepsis), respectively. No difference was found in the protein expression of LCs between 2-hour sepsis group and 6-hour sepsis group, but the protein expression of LCs in severe scald group, 2-hour sepsis group and 6-hour sepsis group differed when compared with control group. Nineteen protein spots expressed discrepancy were sieved and their PMFs were obtained. Twelve protein spots (including 11 proteins) were identified, including Cofilin, peptidyl- prolyl cis-trans isomerase cyclophilin A, ubiquitin, nucleoside diphosphate kinase, glutamate dehydrogenase, selenium binding protein I, beta-actin, peroxiredoxin-6, annexin I, actin-3, cellular retinoic-acid binding protein. CONCLUSION: The proteomics of peripheral blood LCs alters in rabbits with severe burn and Pseudomonas aeruginosa sepsis. The proteins with discrepant expression included 11 proteins, which are related with the folding, assembling, transportation and degradation of proteins, signal transmission, inflammation, immunization, energy metabolism, the proliferation, differentiation and apoptosis of cells. These proteins might be associated with the pathogenesis of severe burn and Pseudomonas aeruginosa sepsis.

MiR-128-3p directly targets VEGFC/VEGFR3 to modulate the proliferation of lymphatic endothelial cells through Ca2+ signaling.

Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation. By using online tools, miR-128 and miR-3916 were predicted as candidate upstream miRNAs which might target VEGFC/VEGFR3. As verified using Immunoblotting assays, miR-128 significantly regulated the protein levels of VEGFC/VEGFR3, whereas miR-3916 only slightly modulated VEGFC and VEGFR3 proteins. Contrary to VEGFC, miR-128 overexpression remarkably suppressed LEC proliferation, Ca2+ release and ERK1/2-Akt signaling; moreover, the effect of VEGFC could be partially attenuated by miR-128. In summary, miR-128 interacts with the 3'-UTR of VEGFC and VEGFR3 to inhibit their expression, thus suppressing LEC proliferation through Ca2+ and ERK1/2-Akt signaling. Taken together, we provided novel experimental basis for miRNA-regulated LEC proliferation through Ca2+ signaling.

Muscular proteomic profiling of deep pressure ulcers reveals myoprotective role of JAK2 in ischemia and reperfusion injury.

Pressure ulcers (PUs) are a complex and serious clinical problem. Deep tissue injury (DTI) is either the outcome or the trigger of deep PUs. However, the cellular and molecular mechanisms that contribute to the pathogenesis of deep PUs remain unclear. In this study, the degeneration characteristics and increased autophagy and apoptosis were observed in deep PU muscle tissues. Muscular proteome of deep PU revealed that a total of 520 proteins were differentially expressed, particularly, JAK2 was down-regulated. Intriguingly, expression of JAK2 in C2C12 myoblasts exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) insult was also distinctly reduced. Ex vivo, we transfected C2C12 myoblasts with lentivirus carrying the JAK2 plasmid and found that JAK2-overexpressed myoblasts exhibited a decrease in autophagy and apoptosis after OGD/R treatment, as well as less cell death. Finally, Western blot analysis determined that p-JAK2, p-AKT, p-mTOR and p-ERK1/2 levels were significantly elevated, accompanied by JAK2 overexpression but without p-STAT3, and inhibition of the AKT and ERK1/2 pathway resulted in elevated apoptosis and/or autophagy. These results demonstrated that JAK2 may play an important protective role in muscular ischemia and reperfusion injury during DTI development by inhibition of autophagy and apoptosis through the AKT and ERK1/2 pathways.

Epidemiologic and clinical characteristics of severe burn patients: results of a retrospective multicenter study in China, 2011-2015.

BACKGROUND: Severe burns injury is a serious pathology, leading to teratogenicity and significant mortality, and it also has a long-term social impact. The aim of this article is to describe the hospitalized population with severe burns injuries in eight burn centers in China between 2011 and 2015 and to suggest future preventive strategies. METHODS: This 5-year retrospective review included all patients with severe burns in a database at eight institutions. The data collected included gender, age, month distribution, etiology, location, presence of inhalation injury, total burn surface area, depth of the burn, the length of hospitalization, and mortality. SPSS 19.0 software was used to analyze the data. RESULTS: A total of 1126 patients were included: 803 (71.3%) male patients and 323 (28.7%) female patients. Scalds were the most common cause of burns (476, 42.27%), followed by fire (457, 40.59%). The extremities were the most frequently affected areas, followed by the trunk. The median length of hospitalization was 30 (15, 52) days. The overall mortality rate was 14.21%. CONCLUSIONS: Although medical centers have devoted intensive resources to improving the survival rates of burn patients, expenditures for prevention and education programs are minimal. Our findings suggest that more attention should be paid to the importance of prevention and the reduction of injury severity. This study may contribute to the establishment of a nationwide burn database and the elaboration of strategies to prevent severe burns injury.

Reconstruction of fingers after electrical injury using lateral tarsal artery flap.

OBJECTIVE: Electrical injuries to the fingers account for the majority of total severe burns that occur each year. While several types of flaps have been used in covering finger defects, all have limitations or disadvantages. The purpose of this study was to introduce our clinical experiences of using the lateral tarsal artery (LTA) flap to successfully restore fingers after electrical injury. PATIENTS AND METHODS: From 2005 to 2012, 10 patients with 14 severe electrical burns to their fingers, including six thumbs and four index and four middle fingers, were treated with LTA flap. The wound size ranged from 2.0×3.0 cm to 3.5×5.0 cm. The flap with free tendon graft was used to repair the tendon defect in four cases, free nerve graft was used to repair the feeling defect in two cases, and the flap with nerve was used to repair the feeling defect in two cases. All the patients were followed up for 3 months to 2 years. RESULTS: All skin flaps adhered successfully and there were no complications. All patients were satisfied with the esthetic appearance and functional outcome of the finger reconstruction. CONCLUSION: LTA flap is a reliable method to restore fingers after severe electrical injuries.