Primary versus secondary cutaneous endometriosis: Literature review and case study.

Cutaneous endometriosis, characterized by the presence of endometrium or endometrial-like tissue outside of the uterine cavity, is an uncommon and chronic disease. Depending on a patient's history, cutaneous endometriosis is classified as either primary cutaneous endometriosis (PCE) or secondary cutaneous endometriosis (SCE). We report a case of SCE presenting with the classic triad of previous caesarean section, subcutaneous nodules at the site of the scar, and pain associated with menstruation. Considering histopathology as the standard, we confirmed a diagnosis of cutaneous endometriosis by ultrasound and histopathology. Furthermore, we compared and analyzed the clinical characteristics of PCE and SCE, the study included 20 and 14 patients with cutaneous endometriosis diagnosed with PCE and SCE respectively. In the PCE group, the mean age of patients at the onset was 33.7 years, while it was 40.6 years in the SCE group. The mean disease-duration time of PCE was shorter than that of SCE (1.3 vs. 2.8 years, P > 0.05). The most common clinical presentation of PCE and SCE was a nodule (90% vs. 86%). The PCE was mainly bleeding with pain (45%), whereas the SCE of only pain and bleeding with pain accounted for the same proportion (45%). The most common sites of PCE and SCE were in the umbilical region (90% vs. 57%, P < 0.05). In our study, some statistically significant difference was found between different types of CE and it may contribute to improve clinicians' understanding of the disease, and perform early diagnosis and treatment.

Four-corners traction combined with continuous everting suture technique as a modification in bicaval anastomosis for orthotopic heart transplantation.

BACKGROUND: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. MATERIALS AND METHODS: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. RESULTS: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. CONCLUSIONS: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.

Chondroid syringoma of the lower back simulating lipoma: A case report.

BACKGROUND: Chondroid syringoma (CS) is a rare tumor of the apocrine or eccrine glands. CS of the lower back is rare, and its clinical manifestations are similar to those of lipoma, which is a common misdiagnosis for this disease. CASE SUMMARY: A 39-year-old woman presented with a 2-year history of an asymptomatic subcutaneous mass on the lower back. The lesions increased progressively over time. The patient denied any history. Dermatological examination showed that there was a subcutaneous mass, ranging from 3-4 cm in diameter, with a clear boundary on the lower back. The surface of the skin was smooth without ulceration or scaling. Histopathologic examination was consistent with the diagnosis of CS. CONCLUSION: CS is a rare tumor of the apocrine or eccrine glands. It usually presents as a wellcircumscribed and single subcutaneous masses. Histopathology showed the tumor was located in the dermis, with nests, sheets, and cords of basal-like cells, mucin deposition, and chondroid structures. We herein report a case of CS located in the lower back. CS of the lower back is rare, and its clinical manifestations are similar to those of lipoma, for which it is commonly misdiagnosed.

Gentiopicroside alleviates cardiac inflammation and fibrosis in T2DM rats through targeting Smad3 phosphorylation.

BACKGROUND: Cardiac fibrosis is a major structural change observed in the heart of patients with type 2 diabetes mellitus (T2DM), ultimately resulting in heart failure (HF). Suppression of inflammation is an effective therapeutic strategy for treating cardiac fibrosis and HF. Gentiopicroside (GPS), the primary component of Gentiana manshurica Kitagawa, possess potent anti-inflammatory activity. However, its cardioprotective role remains elusive. PURPOSE: We explored the potential cardioprotective role of GPS in T2DM rats and its underlying mechanisms. METHODS: T2DM rats built by high-fat diet and streptozotocin were orally administered 25, 50, or 100 mg/kg GPS, daily for 8 weeks. The positive control drug was Metformin (200 mg/kg/day). Primary cardiac fibroblasts (CFs) were induced by high glucose (30 mM) and subsequently treated with GPS (100 µM). Cardiac function and pathological changes were analyzed using echocardiography and histological staining. Potential targets of GPS were predicted using Molecular docking. Real-time PCR as well as western blotting were applied to verify the expression of objective genes. RESULTS: All three doses reduced fasting blood glucose levels, but only 50 and 100 mg/kg GPS improved cardiac function and alleviated inflammation and fibrosis in T2DM rats. GPS (100 mg/kg) exhibited a better effect, similar to that of metformin. Mechanistically, binding between GPS and the MH2 domain of Smad3 blocked high glucose-induced Smad3 phosphorylation, thus attenuating inflammation, oxidative stress, and activation in CFs. CONCLUSION: We, for the first time, demonstrated that GPS improved cardiac function in T2DM rats and elucidated the underlying mechanism through which GPS targeted Smad3 phosphorylation to suppress inflammation and activation in CFs, thereby revealing the potential application of GPS in HF therapy.

A secreted ribonuclease effector from Verticillium dahliae localizes in the plant nucleus to modulate host immunity.

The arms race between fungal pathogens and plant hosts involves recognition of fungal effectors to induce host immunity. Although various fungal effectors have been identified, the effector functions of ribonucleases are largely unknown. Herein, we identified a ribonuclease secreted by Verticillium dahliae (VdRTX1) that translocates into the plant nucleus to modulate immunity. The activity of VdRTX1 causes hypersensitive response (HR)-related cell death in Nicotiana benthamiana and cotton. VdRTX1 possesses a signal peptide but is unlikely to be an apoplastic effector because its nuclear localization in the plant is necessary for cell death induction. Knockout of VdRTX1 significantly enhanced V. dahliae virulence on tobacco while V. dahliae employs the known suppressor VdCBM1 to escape the immunity induced by VdRTX1. VdRTX1 homologs are widely distributed in fungi but transient expression of 24 homologs from other fungi did not yield cell death induction, suggesting that this function is specific to the VdRTX1 in V. dahliae. Expression of site-directed mutants of VdRTX1 in N. benthamiana leaves revealed conserved ligand-binding sites that are important for VdRTX1 function in inducing cell death. Thus, VdRTX1 functions as a unique HR-inducing effector in V. dahliae that contributes to the activation of plant immunity.

Protein kinases Elm1 and Sak1 of Saccharomyces cerevisiae exerted different functions under high-glucose and heat shock stresses.

Phosphorylation catalyzed by protein kinases is the most common and important regulatory pathway in the adaptive physiological responses to the changes in nutrition and environment of yeast. This study focused on the functions of Elm1, Sak1, and Tos3, which are three upstream protein kinases of Snf1 in Saccharomyces cerevisiae, in response to high-glucose and heat shock stresses. Results suggested that changing the gene dosage of ELM1/SAK1/TOS3 had different effects under high-glucose and heat shock stresses. ELM1 and SAK1 overexpressions could enhance the tolerance of S. cerevisiae to high-glucose and heat shock stresses, respectively. Nevertheless, the overexpression of TOS3 decreased the tolerance to high-glucose stress, and a native level of Tos3 was important for the normal adaptation to heat shock condition. The overexpression of ELM1 increased the accumulation of trehalose and ergosterol and altered the composition of fatty acids with altered gene expressions involved in the metabolism of three metabolites. Enhanced resistance to heat shock stress in SAK1 overexpression might be related to the enhanced accumulation of trehalose and ergosterol and upregulated transcription of genes related to the metabolism of trehalose and ergosterol. Furthermore, Elm1 might regulate the metabolism of trehalose, ergosterol, and fatty acids in a Snf1-independent form under high-glucose stress. A Snf1-independent pathway might be involved in the regulation of trehalose metabolism by Sak1 under heat shock condition. However, Sak1 and Snf1 may have an indirect relationship in the regulation of ergosterol synthesis. KEY POINTS: • Altering the gene dosage of ELM1/SAK1/TOS3 had different effects on stress responses • Elm1 regulated high-glucose response in a Snf1-independent manner • Sak1 and Snf1 had an indirect relationship in the regulation of heat shock response.

Disseminated infection by Fusarium solani in acute lymphocytic leukemia: A case report.

BACKGROUND: In recent years, the rate of immunosuppressed patients has increased rapidly. Invasive fungal infections usually occur in these patients, especially those who have had hematological malignances and received chemotherapy. Fusariosis is a rare pathogenic fungus, it can lead to severely invasive Fusarium infections. Along with the increased rate of immune compromised patients, the incidence of invasive Fusarium infections has also increased from the past few years. Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection. CASE SUMMARY: We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin, eyeball, and knee joint during the course of chemotherapy. We performed skin biopsy, microbial cultivation, and molecular biological identification, and the pathogenic fungus was finally confirmed to be Fusarium solani. The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily, and surgical debridement. Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery. The disseminated Fusarium solani infection eventually resolved, and there was no recurrence at the 3 mo follow-up. CONCLUSION: Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection. These are important to prevent progression to a more aggressive infection. Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy. Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.

Role of Elm1, Tos3, and Sak1 Protein Kinases in the Maltose Metabolism of Baker's Yeast.

Glucose repression is a key regulatory system controlling the metabolism of non-glucose carbon source in yeast. Glucose represses the utilization of maltose, the most abundant fermentable sugar in lean dough and wort, thereby negatively affecting the fermentation efficiency and product quality of pasta products and beer. In this study, the focus was on the role of three kinases, Elm1, Tos3, and Sak1, in the maltose metabolism of baker's yeast in lean dough. The results suggested that the three kinases played different roles in the regulation of the maltose metabolism of baker's yeast with differential regulations on MAL genes. Elm1 was necessary for the maltose metabolism of baker's yeast in maltose and maltose-glucose, and the overexpression of ELM1 could enhance the maltose metabolism and lean dough fermentation ability by upregulating the transcription of MALx1 (x is the locus) in maltose and maltose-glucose and MALx2 in maltose. The native level of TOS3 and SAK1 was essential for yeast cells to adapt glucose repression, but the overexpression of TOS3 and SAK1 alone repressed the expression of MALx1 in maltose-glucose and MALx2 in maltose. Moreover, the three kinases might regulate the maltose metabolism via the Snf1-parallel pathways with a carbon source-dependent manner. These results, for the first time, suggested that Elm1, rather than Tos3 and Sak1, might be the dominant regulator in the maltose metabolism of baker's yeast. These findings provided knowledge about the glucose repression of maltose and gave a new perspective for breeding industrial yeasts with rapid maltose metabolism.

Key Insights and Research Prospects at the Dawn of the Population Genomics Era for Verticillium dahliae.

The genomics era has ushered in exciting possibilities to examine the genetic bases that undergird the characteristic features of Verticillium dahliae and other plant pathogens. In this review, we provide historical perspectives on some of the salient biological characteristics of V. dahliae, including its morphology, microsclerotia formation, host range, disease symptoms, vascular niche, reproduction, and population structure. The kaleidoscopic population structure of this pathogen is summarized, including different races of the pathogen, defoliating and nondefoliating phenotypes, vegetative compatibility groupings, and clonal populations. Where possible, we place the characteristic differences in the context of comparative and functional genomics analyses that have offered insights into population divergence within V. dahliae and the related species.Current challenges are highlighted along with some suggested future population genomics studies that will contribute to advancing our understanding of the population divergence in V. dahliae.

Mycobacterium abscessus infection after facial injection of argireline: A case report.

BACKGROUND: The incidence of infection with Mycobacterium abscessus (M. abscessus) has increased in recent years. This increase is partly associated with invasive cosmetic procedures. CASE SUMMARY: The purpose of this case summary is to increase clinicians' awareness of M. abscessus infection and reduce mycobacterial infection caused by cosmetic procedures. We report the case of a 45-year-old woman who received acetyl hexapeptide-8 (argireline) injections in the forehead and temples, and erythema, nodules, and abscesses appeared at the injection sites after one week. The pus specimens were examined by microbiological culture and confirmed to be positive for M. abscessus. Clarithromycin 500 mg twice daily and moxifloxacin 400 mg once daily were administered for 5 mo and the lesions gradually subsided. CONCLUSION: We report here for the first time a case of infection with M. abscessus after argireline injection. This condition is easily misdiagnosed as a common bacterial infection. Microbiological examinations are helpful for diagnosis and standardized cosmetic procedures can prevent infection with M. abscessus.

Effect of overexpression of SNF1 on the transcriptional and metabolic landscape of baker's yeast under freezing stress.

BACKGROUND: Freezing stress is the key factor that affecting the cell activity and fermentation performance of baker's yeast in frozen dough production. Generally, cells protect themselves from injury and maintain metabolism by regulating gene expression and modulating metabolic patterns in stresses. The Snf1 protein kinase is an important regulator of yeast in response to stresses. In this study, we aim to study the role of the catalytic subunit of Snf1 protein kinase in the cell tolerance and dough leavening ability of baker's yeast during freezing. Furthermore, the effects of SNF1 overexpression on the global gene expression and metabolite profile of baker's yeast before and after freezing were analysed using RNA-sequencing and untargeted UPLC - QTOF-MS/MS, respectively. RESULTS: The results suggest that overexpression of SNF1 was effective in enhancing the cell tolerance and fermentation capacity of baker's yeast in freezing, which may be related to the upregulated proteasome, altered metabolism of carbon sources and protectant molecules, and changed cell membrane components. SNF1 overexpression altered the level of leucin, proline, serine, isoleucine, arginine, homocitrulline, glycerol, palmitic acid, lysophosphatidylcholine (LysoPC), and lysophosphatidylethanolamine (LysoPE) before freezing, conferring cells resistance in freezing. After freezing, relative high level of proline, lysine, and glycerol maintained by SNF1 overexpression with increased content of LysoPC and LysoPE. CONCLUSIONS: This study will increase the knowledge of the cellular response of baker's yeast cells to freezing and provide new opportunities for the breeding of low-temperature resistant strains.

High expression of monocarboxylate transporter 4 (MCT 4), but not MCT 1, predicts poor prognosis in patients with non-small cell lung cancer.

BACKGROUND: The monocarboxylate transporter (MCT) family especially MCT1 and MCT4 have been recognized to play an important role in lactate transport, a key glycolytic product. The expression of MCT1 and MCT4 expression was previously found to be related to poor outcome in various cancer types. In this study, we investigated the expression status of MCT1 and MCT4 and their relationship with prognosis in non-small cell lung cancer (NSCLC). METHODS: Expression of MCT4 and MCT1 in NSCLC tumor and adjacent lung tissues were detected by immunohistochemistry. Kaplan-Meier plots were used to evaluate two proteins' prognostic role, and the log-rank test obtained the P value. For multivariate analysis, the Cox proportional-hazards regression method was performed. RESULTS: High MCT4 and MCT1 expression was observed in cancer cells, with a rate of 45% for MCT4 versus 15% for MCT1 among all NSCLC patients. High expression of MCT4, and not MCT1, was associated with worse overall survival (OS) [hazard ratio (HR) =1.96 (1.06-3.75), P=0.032] and progression-free survival (PFS) [HR =1.72 (1.05-2.93), P=0.032] in NSCLC patients. In our multivariate analysis, advanced cancer stage and high MCT4 level were identified as independent predictive indicators for both PFS [HR(MCT4) =1.888 (1.114-3.199), P=0.018 and OS [HR (MCT4) =2.421 (1.271-4.610), P=0.007]. Subgroup and interaction analyses were also performed in different clinical characteristic groups and no significant differences were observed. CONCLUSIONS: High MCT4 expression is a predictive marker for worse outcome in NSCLC patients.

Majocchi's granuloma caused by Trichophyton rubrum after facial injection with hyaluronic acid: A case report.

BACKGROUND: Facial cosmetic procedures become popular for people with a desire to have a younger appearance, and cosmetic technology has developed rapidly over the past several decades. However, increasing complications related to cosmetic injections have been reported, and infection is one of the most serious problems and can cause anxiety and facial injury. We here report a case of Majocchi's granuloma (MG) caused by Trichophyton rubrum after facial injection of hyaluronic acid. CASE SUMMARY: A 37-year-old woman presented to our hospital with a history of red papules, nodules, and abscesses on her left zygomatic arch for 2 mo. She had received a cosmetic injection of hyaluronic acid on the left side of her face prior to the appearance of the lesions. MG caused by Trichophyton rubrum after facial injection of hyaluronic acid was diagnosed based on morphology and molecular biological identification. In vitro antifungal susceptibility testing was conducted according to the Clinical and Laboratory Standards Institute M38-A2 method. Minimal inhibitory concentrations were used to evaluate the antifungal susceptibility. The antifungal agents and their minimal inhibitory concentrations for the strain were terbinafine (< 0.5 µg/mL), itraconazole (0.06 µg/mL), amphotericin B (0.25 µg/mL), fluconazole (32 µg/mL), voriconazole (0.125 µg/mL), posaconazole (0.125 µg/mL), and isavuconazole (0.06 µg/mL). We initially administered 250 mg/d oral terbinafine for 2 mo, but the patient still had painful papules, nodules and abscesses on her face. Then, we adjusted the treatment to itraconazole 400 mg/d for 8 wk based on the in vitro antifungal susceptibility testing results. The skin lesions improved significantly, and there was no recurrence during follow-up. CONCLUSION: This case revealed that facial injection of hyaluronic acid may cause serious MG. Antifungal susceptibility testing should be considered in the treatment of MG caused by Trichophyton rubrum.

Highly efficient replacement of traditional intumescent flame retardants in polypropylene by manganese ions doped melamine phytate nanosheets.

The intumescent flame retardant (IFR) with ammonium polyphosphate (APP) as the main component has many defects in practical applications, more than that, APP can be traced to non-renewable phosphate rock resources. For the foregoing reasons, the melamine phytate supramolecular nanosheet flame retardant incorporating manganese ion (PAMA-Mn) was successfully prepared with a facile and environmental friendly hydrothermal procedure based on renewable bio-based material phytic acid (PA). The flame retardant polypropylene composite (PPI) with 13.5 wt% APP and 4.5 wt% pentaerythritol (PER) failed to the UL-94 test, and its limiting oxygen index (LOI) value was only 26.5%. After 33 wt% of APP was replaced by PAMA-Mn, the PPMn33 incorporating only 18 wt% flame retardant additives passed the UL-94 V-0 rating, and its LOI value was increased to 31.9%. Compared with PP, pHRR and pSPR values of PPMn33 were reduced by 56% and 23%, respectively. The fire retardant mechanism of PPMn33 was thoroughly discussed via a variety of characterization methods. It was found that the peak of the Gram-Schmidt curve of PPMn33 was drastically reduced by 49% relative to that of PPI, indicating a remarkably decrease of combustible volatile products owing to the incorporation of PAMA-Mn, thereby rapidly reducing the fire hazard risk.

Enhanced multi-stress tolerance and glucose utilization of Saccharomyces cerevisiae by overexpression of the SNF1 gene and varied beta isoform of Snf1 dominates in stresses.

BACKGROUND: The Saccharomyces cerevisiae Snf1 complex is a member of the AMP-activated protein kinase family and plays an important role in response to environmental stress. The α catalytic subunit Snf1 regulates the activity of the protein kinase, while the ß regulatory subunits Sip1/Sip2/Gal83 specify substrate preferences and stress response capacities of Snf1. In this study, we aim to investigate the effects of SNF1 overexpression on the cell tolerance and glucose consumption of S. cerevisiae in high glucose, ethanol, and heat stresses and to explore the valid Snf1 form in the light of ß subunits in these stresses. RESULTS: The results suggest that overexpression of SNF1 is effective to improve cell resistance and glucose consumption of S. cerevisiae in high glucose, ethanol, and heat stresses, which might be related to the changed accumulation of fatty acids and amino acids and altered expression levels of genes involved in glucose transport and glycolysis. However, different form of ß regulatory subunits dominated in stresses with regard to cell tolerance and glucose utilization. The Sip1 isoform was more necessary to the growth and glucose consumption in ethanol stress. The glucose uptake largely depended on the Sip2 isoform in high sugar and ethanol stresses. The Gal83 isoform only contributed inferior effect on the growth in ethanol stress. Therefore, redundancy and synergistic effect of ß subunits might occur in high glucose, ethanol, and heat stresses, but each subunit showed specificity under various stresses. CONCLUSIONS: This study enriches the understanding of the function of Snf1 protein kinase and provides an insight to breed multi-stress tolerant yeast strains.

Epidemiologic and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China: A descriptive survey report.

BACKGROUND: The epidemiologic and clinical characteristics of heart transplant (HTx) recipients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We studied the characteristics of HTx recipients from December 20, 2019, to February 25, 2020, in an effort to understand their risk and outcomes. METHODS: All accessible HTx recipients were included in this single-center retrospective study. We collected information on the recipients using a web-based questionnaire as well as the hospital database. RESULTS: We followed 87 HTx recipients (72.4% were men, and the average age was 51 years). A total of 79 recipients resided in Hubei, and 57 recipients had a Wuhan-related history of travel or contact. Most took precautionary measures while in contact with suspicious crowds, and 96.6% of the families and communities undertook prevention and quarantine procedures. Four upper airway infections were reported, and 3 of them tested negative for SARS-CoV-2 (the fourth recovered and was not tested). All cases were mild and successfully recovered after proper treatment. Laboratory results of 47 HTx cases within the last 2 months were extracted. Of these, 21.3% of recipients had pre-existing lymphopenia, and 87.2% of recipients had a therapeutic concentration of tacrolimus (5-12 ng/ml). Liver and kidney insufficiency was seen in 5 and 6 recipients, respectively. CONCLUSION: HTx recipients who practiced appropriate prevention measures had a low rate of infection with SARS-CoV-2 and transition to the associated disease COVID-19. These early data will require confirmation as the pandemic establishes around the world.

Avß3 Single-Stranded DNA Aptamer Attenuates Vascular Smooth Muscle Cell Proliferation and Migration via Ras-PI3K/MAPK Pathway.

OBJECTIVES: To observe the effect of avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. METHODS: In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. RESULTS: In the present study, we found that avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. P < 0.05). Avß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. P < 0.05). AvP < 0.05). Av. CONCLUSIONS: The findings suggest that avß3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.ß3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism.

Avß3 single-stranded DNA aptamer attenuates vascular restenosis via Ras-PI3K/MAPK pathway in rats after percutaneous transluminal coronary angioplasty.

Our aim was to investigate the effect of avß3 single-stranded DNA aptamer (avß3 ssDNA) on vascular restenosis in rats after percutaneous transluminal coronary angioplasty (PTCA) via the Ras-PI3K/MAPK pathway. Sixty Sprague-Dawley rats were randomly divided into six groups: sham-operated, PTCA, PTCA+cilengitide (18 mg/kg, n = 8), and avß3 ssDNA treatment at 50, 100, and 200 µg/kg. Hematoxylin-eosin staining was performed to evaluate the successful establishment of the PTCA model and to assess the degree of intimal hyperplasia. Immunofluorescence and in situ hybridization were carried out to observe the level of avß3. Immunohistochemistry was used to detect the expression of E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA), angiotensin 1 (ANG1), and ANG2. The expression of osteopontin (OPN), focal adhesion kinase (FAK), Ras, mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), signal transducer and activator of transcription 1 (STAT1), and GTPase was observed by the western blot and quantitative reverse transcription polymerase chain reaction. Compared with rats subjected to PTCA only, those treated with avß3 ssDNA showed significantly decreased vascular occlusion rate (P < .05). The protein expression of avß3, OPN, p-FAK, ANG2, and E-cadherin was significantly increased by avß3 ssDNA (P < .05), while the levels of ANG1, α-SMA, N-cadherin Ras, MAPK, PI3K, STAT1, and GTPase were significantly decreased (P < .05). Avß3 ssDNA reduced the proliferation, migration, epithelial-mesenchymal transition, and vascular remodeling of vascular smooth muscle cells, and the mechanism may be related to the Ras-PI3K/MAPK pathway.

The Verticillium dahliae Sho1-MAPK pathway regulates melanin biosynthesis and is required for cotton infection.

Verticillium dahliae is a soil-borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses is well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild-type strain. Furthermore, VdSho1 regulates melanin biosynthesis by a signalling mechanism requiring a kinase-kinase signalling module of Vst50-Vst11-Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50-Vst11-Vst7 module regulates VdSho1-mediated plant penetration and melanin production in V. dahliae, contributing to virulence.

Histone deacetylase SIRT6 regulates chemosensitivity in liver cancer cells via modulation of FOXO3 activity.

Liver cancer is the leading cause of cancer­related mortality worldwide and its incidence is increasing. Considerable effort has been made in recent decades to improve the diagnosis and treatment of liver cancer. Advanced liver cancer often exhibits a poor response to chemotherapy and poor prognosis due to acquired chemoresistance and tumor recurrence. Understanding the precise molecular mechanisms that are responsible for chemotherapeutic drug­induced cell death could potentially identify novel therapeutic targets and improve liver cancer treatment. In the present study, it was demonstrated that in response to doxorubicin, the most frequently used chemical compound for liver cancer treatment, histone deacetylase sirtuin 6 (SIRT6) is specifically downregulated. This enables forkhead box O3 (FOXO3) upregulation, translocation into the nucleus and increased expression of its target genes p27 and Bim, which further induce apoptosis. Overexpression of SIRT6, but not enzyme­inactivated mutants, prevents FOXO3 translocation into the nucleus and doxorubicin­induced cell death. SIRT6 interacts with FOXO3 and this interaction increases FOXO3 ubiquitination and decreases its stability. Finally, it was identified that the effect of SIRT6 in preventing doxorubicin­induced cell death requires FOXO3. Overexpression of SIRT6 could not prevent doxorubicin­induced cell death in FOXO3­knockdown cells. Therefore, it was concluded that SIRT6 plays a central role in determining doxorubicin­induced cell death via modulation of FOXO3 activity. Therapeutic targeting of SIRT6 and/or FOXO3 may offer novel strategies for treatment of liver cancer.