Pretreatment with platelet-rich plasma protects against ischemia-reperfusion induced flap injury by deactivating the JAK/STAT pathway in mice.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a major cause of surgical skin flap compromise and organ dysfunction. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, with tissue regenerative potential. PRP has shown promise in multiple I/R-induced tissue injuries, but its effects on skin flap injury remain unexplored. METHODS: We evaluated the effects of PRP on I/R-injured skin flaps, optimal timing of PRP administration, and the involved mechanisms. RESULTS: PRP protected against I/R-induced skin flap injury by improving flap survival, promoting blood perfusion and angiogenesis, suppressing oxidative stress and inflammatory response, and reducing apoptosis, at least partly via deactivating Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signalling pathway. PRP given before ischemia displayed overall advantages over that given before reperfusion or during reperfusion. In addition, PRP pretreatment had a stronger ability to reverse I/R-induced JAK/STAT activation and apoptosis than AG490, a specific inhibitor of JAK/STAT signalling. CONCLUSIONS: This study firstly demonstrates the protective role of PRP against I/R-injured skin flaps through negative regulation of JAK/STAT activation, with PRP pretreatment showing optimal therapeutic effects.

Diagnosis and treatment of diabetic foot ulcer complicated with lower extremity vasculopathy: Consensus recommendation from the Chinese Medical Association (CMA), Chinese Medical Doctor Association (CMDA).

Diabetic foot ulcer complicated with lower extremity vasculopathy is highly prevalent, slow healing and have a poor prognosis. The final progression leads to amputation, or may even be life-threatening, seriously affecting patients' quality of life. The treatment of lower extremity vasculopathy is the focus of clinical practice and is vital to improving the healing process of diabetic foot ulcers. Recently, a number of clinical trials on diabetic foot ulcers with lower extremity vasculopathy have been reported. A joint group of Chinese Medical Association (CMA) and Chinese Medical Doctor Association (CMDA) expert representatives reviewed and reached a consensus on the guidelines for the clinical diagnosis and treatment of this kind of disease. These guidelines are based on evidence from the literature and cover the pathogenesis of diabetic foot ulcers complicated with lower extremity vasculopathy and the application of new treatment approaches. These guidelines have been put forward to guide practitioners on the best approaches for screening, diagnosing and treating diabetic foot ulcers with lower extremity vasculopathy, with the aim of providing optimal, evidence-based management for medical personnel working with diabetic foot wound repair and treatment.

PGD: a machine learning-based photosynthetic-related gene detection approach.

BACKGROUND: The primary determinant of crop yield is photosynthetic capacity, which is under the control of photosynthesis-related genes. Therefore, the mining of genes involved in photosynthesis is important for the study of photosynthesis. MapMan Mercator 4 is a powerful annotation tool for assigning genes into proper functional categories; however, in maize, the functions of approximately 22.15% (9520) of genes remain unclear and are labeled "not assigned", which may include photosynthesis-related genes that have not yet been identified. The fast-increasing usage of the machine learning approach in solving biological problems provides us with a new chance to identify novel photosynthetic genes from functional "not assigned" genes in maize. RESULTS: In this study, we proved the ensemble learning model using a voting eliminates the preferences of single machine learning models. Based on this evaluation, we implemented an ensemble based ML(Machine Learning) methods using a majority voting scheme and observed that including RNA-seq data from multiple photosynthetic mutants rather than only a single mutant could increase prediction accuracy. And we call this approach "A Machine Learning-based Photosynthetic-related Gene Detection approach (PGD)". Finally, we predicted 716 photosynthesis-related genes from the "not assigned" category of maize MapMan annotation. The protein localization prediction (TargetP) and expression trends of these genes from maize leaf sections indicated that the prediction was reliable and robust. And we put this approach online base on google colab. CONCLUSIONS: This study reveals a new approach for mining novel genes related to a specific functional category and provides candidate genes for researchers to experimentally define their biological functions.

Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1ß), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1ß/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.

AoStuA, an APSES transcription factor, regulates the conidiation, trap formation, stress resistance and pathogenicity of the nematode-trapping fungus Arthrobotrys oligospora.

The APSES protein family comprises a conserved class of fungus-specific transcriptional regulators. Some members have been identified in partial ascomycetes. In this study, the APSES protein StuA (AoStuA) of the nematode-trapping fungus Arthrobotrys oligospora was characterized. Compared with the wild-type (WT) strain, three ΔAoStuA mutants grew relatively slowly, displayed a 96% reduction in sporulation capacity and a delay in conidial germination. The reduced sporulation capacity correlated with transcriptional repression of several sporulation-related genes. The mutants were also more sensitive to chemical stressors than the WT strain. Importantly, the mutants were unable to produce mycelial traps for nematode predation. Moreover, peroxisomes and Woronin bodies were abundant in the WT cells but hardly found in the cells of those mutants. The lack of such organelles correlated with transcriptional repression of some genes involved in the biogenesis of peroxisomes and Woronin bodies. The transcript levels of several genes involved in the cAMP/PKA signalling pathway were also significantly reduced in the mutants versus the WT strain, implicating a regulatory role of AoStuA in the transcription of genes involved in the cAMP/PKA signalling pathway that regulates an array of cellular processes and events. In particular, AoStuA is indispensable for A. oligospora trap formation and virulence.

Prolonged skin grafts survival time by IFN-γ in allogeneic skin transplantation model during acute rejection through IFN-γ/STAT3/IDO pathway in epidermal layer.

Allogeneic skin transplantation is the life-saving therapy for multiple diseases, including extensive burn, large-scale trauma and certain post-surgical complications. However, acute rejection impedes clinical application of allogeneic skin transplantation. Although a lot of novel immunosuppressant drugs have been developed, there is still great need for ideal therapy with less complication and more therapeutic effects. Here, we found interferon gamma (IFN-γ) as an immunomodulatory cytokine prolonged the survival time of allografts from (8.50 ±â€¯1.517) days to (14.83 ±â€¯2.714) days at best. Indoleamine-2, 3-dioxygenase (IDO) has been proposed to play key roles in induction of immune tolerance. Using in vitro tissue culture and primary keratinocytes and fibroblasts, we investigated the regulatory effects of IFN-γ on the IDO expression. IFN-γ upregulated IDO expression through STAT3 phosphorylation and this upregulation was reduced by abolition of STAT3 phosphorylation through a STAT3 phosphorylation inhibitor. Interestingly, IFN-γ induced IDO expression predominately in epidermis rather than dermis. In consistent with these results, IFN-γ significantly triggered IDO expression in keratinocytes but not fibroblasts. Taken together, this suggests that IFN-γ might be a potential immunomodulatory drug in acute rejection and keratinocytes in epidermis may play a main role in immune tolerance after allogeneic skin transplantation.

Curcumin pretreatment prevents hydrogen peroxide-induced oxidative stress through enhanced mitochondrial function and deactivation of Akt/Erk signaling pathways in rat bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs)-based therapy has emerged as a desirable modality for the treatment of tissue injury with promising therapeutic effects; however, low survival rate of transplanted cells due to harsh microenvironment with hypoxia and oxidative stress results in hampered therapeutic benefits of this therapy. Curcumin, a natural bioactive product, is a dietary component which has gained increasing attention owing to its beneficial health properties. Here, we reported the protective effects of curcumin pretreatment on BMSCs injury induced by hydrogen peroxide (H2O2), which was used as ROS source of oxidative stress in vitro. We found that curcumin pretreatment remarkably inhibited H2O2-induced cell viability reduction, LDH leakage, and cell apoptosis in BMSCs. Moreover, curcumin pretreatment prevented H2O2-induced mitochondrial dysfunction via suppressing adenosine triphosphate loss, reactive oxygen species accumulation, and membrane potential decline. In addition, curcumin pretreatment markedly reduced the phosphorylation levels of Akt and Erk1/2. Taken together, our investigations demonstrated that curcumin pretreatment conferred BMSCs the ability to survive from H2O2-induced oxidative stress, which might attribute to its prevention of mitochondrial dysfunction and deactivation of Akt and Erk1/2 signaling pathways. Thus, this study sheds more light on the pharmacological mechanisms of curcumin, and suggests that BMSCs preconditioned with curcumin might be an effective way for cell therapy in tissue repair treatment.

Intense pulsed light is effective in treating postburn hyperpigmentation and telangiectasia in Chinese patients.

Intense pulsed light (IPL) has been used to treat postinflammatory hyperpigmentation and telangiectasia in Fitzpatrick type I -II skin. However, its therapeutic effects after superficial second-degree burns in Asian populations with Fitzpatrick type III-IV skin are uncertain. Thirty-five Han Chinese patients with facial or hand hyperpigmentation and telangiectasia due to second-degree fire burns received treatment with IPL. Each patient underwent 2-6 treatments over 3-5 weeks. The laser wavelength was 560-615 nm. Skin pigmentation was evaluated by two plastic surgeons as well as by the patients themselves (self-evaluation) before treatment at the end of the treatment cycle and 1 year after the first treatment. Blood flow in telangiectasia skin was measured by laser Doppler flow. The results showed that IPL significantly lessened hyperpigmentation so that close to normal skin color was achieved after the treatment cycles, and pigmentation did not reoccur 1 year after the first treatment. Approximately 82.9% of the patients were satisfied with their treatment outcomes. There were no post-treatment complications. Doppler showed a significant decreased blood flow in telangiectasia after treatment. In conclusion, IPL is an effective and safe modality for Chinese patients with hyperpigmentation and telangiectasia after fire burns.

Murine Sertoli cells promote the development of tolerogenic dendritic cells: a pivotal role of galectin-1.

Sertoli cells (SCs) possess inherent immunosuppressive properties and are major contributors to the immunoprivileged status of mammalian testis. SCs have been reported to inhibit the activation of B cells, T cells and natural killer cells but not dendritic cells (DCs). Herein, we present evidence that co-culture with SCs results in a persistent state of DC immaturity characterized by down-regulation of the surface molecules I-A/E, CD80, CD83, CD86, CCR7 and CD11c, as well as reduced production of pro-inflammatory cytokines. SC-conditioned DCs (SC-DCs) displayed low immunogenicity and enhanced immunoregulatory functions, including the inhibition of T-cell proliferation and the promotion of Foxp3(+) regulatory T-cell development. Mechanistically, the activation of p38, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was suppressed in SC-DCs. More importantly, we demonstrate that galectin-1 secreted by SCs plays a pivotal role in the differentiation of functionally tolerogenic SC-DCs. These findings further support the role of SCs in maintaining the immunoprivileged environment of the testis and provide a novel approach to derive tolerogenic DCs, which may lead to alternative therapeutic strategies for the treatment of immunopathogenic diseases.

Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats.

Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.

Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-ß/Smad pathway.

The ethanolic extract of Resina Draconis (RDEE) has been reported beneficial to normal wound healing yielding more regularly arranged collagen fibres. Loureirin B, a major component in RDEE, has been supposed to be effective on the prevention and treatment of pathological scars. To investigate the therapeutic effects of loureirin B on hypertrophic scar (HS), fibroblasts from human HS and normal skin (NS) were isolated. Results showed that loureirin B dose-dependently downregulated both mRNA and protein levels of type I collagen (ColI), type III collagen (ColIII) and α-smooth muscle actin (α-SMA) in HS fibroblasts. Loureirin B also suppressed fibroblast proliferative activity and redistributed cell cycle, but did not affect cell apoptosis. In vivo rabbit ear scar model, loureirin B significantly improved the arrangement and deposition of collagen fibres, decreased protein levels of ColI, ColIII and α-SMA and suppressed myofibroblast differentiation and scar proliferative activity. In NS fibroblasts, loureirin B effectively inhibited TGF-ß1-induced upregulation of ColI, ColIII and α-SMA levels, myofibroblast differentiation and the activation of Smad2 and Smad3. Loureirin B also affected mRNA levels of major MMPs and TIMPs in TGF-ß1-stimulated fibroblasts. Taken together, this study demonstrates that loureirin B could downregulate the expression of fibrosis-related molecules by regulating MMPs and TIMPs levels, inhibit scar fibroblast proliferation and suppress TGF-ß1-induced fibrosis, during which TGF-ß1/Smad2/3 pathway is likely involved. These findings suggest that loureirin B is a potential therapeutic compound for HS treatment.

Allogeneic Adipose-Derived Stem Cells Protect Fat Grafts at the Early Stage and Improve Long-Term Retention in Immunocompetent Rats.

BACKGROUND: Syngeneic adipose-derived stem cells (ASCs) promote the survival of fat grafts. But it is unclear whether allogeneic ASCs have a similar protective effect. In this study, we investigated the protective effect of allogeneic ASCs in a fat graft model of immunocompetent rats. METHODS: Syngeneic and allogeneic ASCs were derived from Lewis (LEW) and Norway-Brown rats, respectively. Fifty-four LEW rats were divided into three groups. Each LEW rat was injected subcutaneously at two paravertebral spots with adipose granules premixed with DMEM (AFT group), syngeneic ASCs (SYNG group), or allogeneic ASCs (ALLG group). Fat grafts were harvested at 7 and 14 days to examine apoptosis rates and immunochemistry staining was performed for Perilipin A and CD34. At 3 months, fat graft volume retentions were measured. The proportion of regulatory T (Treg) cells and the ratio of CD4/CD8 cells in blood were analyzed at 7 days. RESULTS: Expression of Perilipin A and CD34 was higher in the ALLG group than the AFT group at 14 days (P < 0.05). The apoptosis rate in the ALLG group decreased in comparison with the AFT group at 7 and 14 days (P < 0.05). At 3 months, allogeneic ASCs increased fat graft volume retentions (P < 0.05). No difference was found in the proportion of Treg cells and CD4/CD8 cells ratio between groups. There were no statistically significant difference between ALLG and SYNG groups at all time points (P > 0.05). CONCLUSIONS: Allogeneic ASCs protected fat grafts at the early stage and improved long-term volume retention in the fat graft model of immunocompetent rats with no or little obvious immune rejection.

Insulin protects against damage to pulmonary endothelial tight junctions after thermal injury: relationship with zonula occludens-1, F-actin, and AKT activity.

Intensive insulin therapy during critical illness protects the endothelium and thereby prevents organ failure. This study tested the hypothesis that insulin directly affects the attenuation of burn injury-induced damage to pulmonary endothelial tight junction and investigated the underlying mechanisms. Sprague Dawley rats with severe burn injury were randomized to treatment with insulin dissolved in normal saline (maintenance of blood glucose at a level between 5.0 and 7.0 mmol/L) or normal saline alone (in vivo treatment). Pulmonary damage was evaluated. Rat pulmonary microvascular endothelial cells were treated with 20% burn serum or 20% burn serum + insulin (in vitro treatment). Selected cultures were pretreated with phosphatidylinositol 3-kinase/protein kinase B (AKT) inhibitor (LY294002). Permeability was assessed by migration of bovine serum albumin across cell monolayers. Cells were stained with rhodamine phalloidin and were examined. Cell extracts were obtained to assess zonula occludens-1, occludin, and phosphorylated AKT levels by immunoblotting. Treatment with insulin attenuated the pulmonary edema, hemorrhage, and inflammatory cell infiltration of rats with severe burn injury. Burn serum significantly enhanced monolayer permeability to albumin, whereas treatment with insulin (10(-7 ) mol/L) limited this effect. Meanwhile, insulin (10(-7 ) mol/L) reduced burn serum-induced F-actin stress fiber formation and decreased zonula occludens-1 expression. LY294002 decreased cytoplasmic AKT phosphorylation and inhibited the protection effects of insulin. Through the phosphatidylinositol 3-kinase/AKT pathway, insulin independent of glucose toxicity can attenuate increased pulmonary endothelial permeability induced by burn injury. The effect is attributed to the attenuation of the architectural disruption of protein components of the endothelial tight junction. This result is useful in inhibiting multiple organ failure after burn injury.

Malate synthase gene AoMls in the nematode-trapping fungus Arthrobotrys oligospora contributes to conidiation, trap formation, and pathogenicity.

Malate synthase (Mls), a key enzyme in the glyoxylate cycle, is required for virulence in microbial pathogens. In this study, we identified the AoMls gene from the nematode-trapping fungus Arthobotrys oligospora. The gene contains 4 introns and encodes a polypeptide of 540 amino acids. To characterize the function of AoMls in A. oligospora, we disrupted it by homologous recombination, and the ΔAoMls mutants were confirmed by PCR and Southern blot analyses. The growth rate and colony morphology of the ΔAoMls mutants showed no obvious difference from the wild-type strains on potato dextrose agar (PDA) plate. However, the disruption of gene AoMls led to a significant reduction in conidiation, failure to utilize fatty acids and sodium acetate for growth, and its conidia were unable to germinate on minimal medium supplemented with sodium oleate. In addition, the trap formation was retarded in the ΔAoMls mutants, which only produced immature traps containing one or two rings. Moreover, the nematicidal activity of the ΔAoMls mutants was significantly decreased. Our results suggest that the gene AoMls plays an important role in conidiation, trap formation and pathogenicity of A. oligospora.

Limited debridement combined with ReCell® Techniques for deep second-degree burns.

BACKGROUND: The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep second-degree burn wounds. METHOD: A total of 20 patients suffered with deep second-degree burns less than 10% of total body surface area (TBSA) who were admitted to our department, from June 2019 to June 2021, participated in this study. These patients first underwent limited debridement with an electric/pneumatic dermatome, followed by the ReCell® technique for secondary wounds. Routine treatment was applied to prevent scarring after the wound healed. Clinical outcomes were scored using the Vancouver Scar Scale (VSS). RESULTS: All wounds of the patients healed completely. One patient developed an infection in the skin graft area and finally recovered by routine dressing changes. The average healing time was 12 days (range: 10-15 days). The new skin in the treated area was soft and matched the colour of the surrounding normal skin and the VSS score ranged from 3~5 for each patient. Of the 20 patients, 19 were very satisfied and 1 was satisfied. CONCLUSIONS: This article reports a useful treatment method that combines electric dermatome-dependent limited debridement and the ReCell® technique for the treatment of deep second-degree burn wounds. It is a feasible and effective strategy that is easy to implement and minimally invasive, and it is associated with a short healing time, mild scar formation and little damage to the donor skin area.

Vascularized Omentum Lymphatic Transplantation as a Treatment for Chronic Inguinal Ulceration and Lymphedema.

Background: After tumor resection, lymphadenectomy, and radiotherapy, recurrent lymphatic fluid leakage and infection can occur in the inguinal region, contributing to severe localized tissue fibrosis. When wounds form in this region, they tend to heal slowly over extended periods, and no optimal approach for treating these complex wounds has yet been established. Methods: Groin wound debridement and dissection of the vessels in the wound recipient site were performed by the burn surgeon. A general surgeon performed the laparoscopic partial omentum excision. One portion of the omentum was used to fill the large inguinal space, whereas the other portion was laid flat on the wound sites in the groin and anterior perineum to facilitate the restoration of appropriate lymphatic fluid reflux. The vessels of the omentum were microsurgically anastomosed with the vessels in the recipient site. Thin split-thickness slices of skin were then taken from this donor site based on the size of the wound. Results: After the successful establishment of revascularization between the flap and recipient sites, lymphatic fluid leakage was not observed in this patient. No inguinal wounding or lymphatic exudate were evident in the patient during follow-up, and significant improvements in lymphedema of the lower extremities were evident. Conclusions: In this article, we discuss the advantages and disadvantages of vascularized omentum lymphatic transplantation. Overall, this procedure represents a promising new approach for the treatment of refractory wounds caused by lymphatic fistulas.

A Scalable and Robust Personal Health Management Textile with Multiple Desired Thermal Functions and Electromagnetic Shielding.

The development of functional textiles combining conventional apparel with advanced technologies for personal health management (PHM) has garnered widespread attention. However, the current PHM textiles often achieve multifunctionality by stacking functional modules, leading to poor durability and scalability. Herein, a scalable and robust PHM textile is designed by integrating electrical, radiative, and solar heating, electromagnetic interference (EMI) shielding, and piezoresistive sensing performance onto cotton fabric. This is achieved through an uncomplicated screen-printing process using silver paste. The conductivity of the PHM textile is ≈1.6  ×  104 S m-1, ensuring an electric heating temperature of ≈134 °C with a low voltage of 1.7 V, as well as an EMI shielding effectiveness of ≈56 dB, and human motion monitoring performance. Surprisingly, the radiative/solar heating capability of the PHM textile surpasses that of traditional warm leather. Even after undergoing rigorous physical and chemical treatments, the PHM textile maintains terrific durability. Additionally, the PHM textile possesses maneuverable scalability and comfortable wearability. This innovative work opens up new avenues for the strategic design of PHM textiles and provides an advantageous guarantee of mass production.

Characterization and functional analyses of the chitinase-encoding genes in the nematode-trapping fungus Arthrobotrys oligospora.

Nematode-trapping fungi can secrete many extracellular hydrolytic enzymes such as serine proteases and chitinases to digest and penetrate nematode/egg-cuticles. However, little is known about the structure and function of chitinases in these fungi. In this study, 16 ORFs encoding putative chitinases, which all belong to glycoside hydrolase (GH) family 18, were identified from the Arthrobotrys oligospora genome. Bioinformatics analyses showed that these 16 putative chitinases differ in their functional domains, molecular weights and pI. Phylogenetic analysis grouped these A. oligospora chitinases into four clades: clades I, II, III and IV, respectively, including an A. oligospora-specific subclade (Clade IV-B) that contained high-molecular weight chitinases (≥100 kDa). Transcriptional analysis of A. oligospora chitinases suggested that the expression of most chitinases was repressed by carbon starvation, and all chitinases were up-regulated under nitrogen starvation. However, chitinase AO-190 was up-regulated under carbon and/or nitrogen starvation. Moreover, several chitinases (such as AO-59, AO-190 and AO-801) were up-regulated in the presence of chitinous substrates or a plant pathogenic fungus, indicating that they could play a role in biocontrol applications of A. oligospora. Our results provided a basis for further understanding the functions, diversities and evolutionary relationships between chitinase genes in nematode-trapping fungi.

Deletion of regulatory T cells supports the development of intestinal ischemia-reperfusion injuries.

BACKGROUND: Ischemia-reperfusion injury (IRI) of the intestine is associated with high morbidity and mortality in surgical and trauma patients. T cells participate in the pathogenesis of intestinal IRI, and T-cell depletion has been shown to inhibit inflammatory responses and diminish intestinal damage. However, the mechanism by which T cells contribute to intestinal IRI is not completely understood. Regulatory T cells (Tregs) are a specific subset of T cells that suppress immune responses and protect against tissue injuries. We hypothesized that Tregs might be involved in intestinal IRI. MATERIALS AND METHODS: We subjected C57/Bl6 mice to 30 min of ischemia by clamping the superior mesenteric artery followed by reperfusion. Animals were pretreated with the anti-CD25 monoclonal antibody or adoptive transfer of Tregs before induction of IRI. The number of inflammatory cells, the level of inflammatory factors, and intestinal permeability were assessed. RESULTS: Partial depletion of Tregs with an anti-CD25 monoclonal antibody potentiated intestinal permeability induced by IRI. The Treg-depleted mice showed more neutrophils and CD4(+) T cells. In addition, depletion of Tregs led to enhanced secretion of tumor necrosis factor-α, interferon-gamma, and interleukin (IL)-4 and reduced levels of IL-10. Furthermore, we performed adoptive transfer of Tregs and found that transfer of Tregs significantly inhibited the ischemia-reperfusion-induced increase in intestinal permeability. CONCLUSIONS: Our study indicated that Tregs participate in intestinal inflammatory responses induced by IRI and that targeting Tregs could be a novel therapeutic approach to intestinal IRI.

Inhibition of Na+/H+ exchanger 1 by cariporide alleviates burn-induced multiple organ injury.

BACKGROUND: Severe burns initiate an inflammatory response characterized by the upregulation of proinflammatory cytokine, which contributes to multiple organ injury. Na(+)/H(+) exchanger 1 (NHE1) plays a significant role in several inflammatory processes. This study was designed to investigate the role of NHE1 in burn-induced inflammation and multiple organ injury. MATERIALS AND METHODS: Rats were subjected to a 30% total body surface area full-thickness burn. Cariporide was used to assess the function of NHE1 in burn-induced multiple organ injury by biochemical parameters, histologic changes, and inflammatory cytokine production. RESULTS: We found that NHE1 expression was significantly increased after burn injury. Inhibition of NHE1 by cariporide attenuated burn-induced edema and tissue injury in heart, lung, kidney, and small intestine. Cariporide also inhibited plasma levels of tumor necrosis factor α, interleukin 6, and myeloperoxidase activity. CONCLUSIONS: These results indicate that NHE1 inhibition prevents burn-induced multiple organ injury. The salutary effects afforded by NHE1 inhibition, at least in part, are mediated by attenuating systemic inflammatory response.