Carvacrol enhances antioxidant activity and slows down cell wall metabolism by maintaining the energy level of 'Guifei' mango.

BACKGROUND: Postharvest mango fruit are highly susceptible to rapid ripening, softening and senescence, greatly limiting their distribution. In this study, we evaluated the potential effects of carvacrol (0.06 g L-1) on mango (25 ± 1 °C) and the mechanisms by which it regulates antioxidant activity, energy and cell wall metabolism. RESULTS: The results showed that carvacrol treatment delayed the 'Guifei' mango color transformation (from green to yellow) and the decrease in firmness, titratable acidity, weight loss and soluble solids content, and suppressed the increase in relative conductivity, malondialdehyde content and reactive oxygen species (H2O2 and O2 ·-) as well as enhancing antioxidant activity. In addition, carvacrol treatment increased ascorbic acid and reduced glutathione levels, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase activities in mango. Meanwhile, energy level (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate and energy charge) content and energy metabolizing enzyme activities (H+-ATPase, Ca2+-ATPase, succinate dehydrogenasepears and cytochrome C oxidase) were increased on carvacrol treatment, which resulted in the maintenance of higher energy levels. Finally, the application of carvacrol was effective in maintaining firmness and cell wall components by inhibiting the activities of polygalacturonase, cellulase, pectin methyl esterase and ß-galactosidase. CONCLUSION: The current study demonstrates that carvacrol effectively delays the ripening and softening of mangoes by modulating energy metabolism and cell wall dynamics through the attenuation of oxidative stress. © 2024 Society of Chemical Industry.

Maintaining quality of postharvest green pepper fruit using melatonin by regulating membrane lipid metabolism and enhancing antioxidant capacity.

Green pepper quality often deteriorates during storage because of membrane lipid damage and oxidative stress. This study investigated the effects of exogenous melatonin (MT) on green pepper storage quality, membrane lipids, and antioxidant metabolism. The results showed that MT increased the activities of superoxide dismutase, catalase, ascorbate peroxidase, peroxidase, monodehydroascorbate reductase, and dehydroascorbate reductase in green peppers compared to the control group. It upregulated expression of multiple enzymes; reduced accumulation of reactive oxygen species such as dehydroascorbic acid, H2O2, and O2.-; and maintained high ascorbic acid, glutathione, coenzyme II, and nicotinamide adenine dinucleotide while reducing oxidized glutathione levels. In addition, MT decreased lipoxygenase and phospholipase D activities, downregulated ReLOX and RePLD expression, and delayed the degradation of phosphatidylcholine, phosphatidylethanolamine, and oleic, linoleic, and linolenic acids in green peppers. These results suggest that MT helps to improve the chilling injury and quality of green peppers and extends shelf life.

Thymol application delays the decline of fruit quality in blueberries via regulation of cell wall, energy and membrane lipid metabolism.

In this study, we evaluated the potential for exogenous thymol to slow this decline by measuring the effects of thymol application on cell wall, energy, and membrane lipid metabolism. The results showed that thymol application improved the preservation of the total soluble solids, titratable acidity, decay rate, and anthocyanin content, and effectively inhibited the accumulation of O2·-, H2O2, and malondialdehyde in blueberries during storage. Thymol application also effectively maintained fruit firmness, cell wall structure, and energy levels, while delaying the degradation of membrane phospholipids and unsaturated fatty acids during the storage of post-harvest blueberries. Therefore, exogenous thymol can maintain the quality of blueberry fruits by regulating energy and membrane lipid metabolism and reducing cell wall degradation. Thus, thymol-treatment could be a suitable biocontrol agent for maintaining blueberry quality and extending blueberry fruit storage life.

Advances in the Understanding of Postharvest Physiological Changes and the Storage and Preservation of Pitaya.

Highly prized for its unique taste and appearance, pitaya is a tasty, low-calorie fruit. It has a high-water content, a high metabolism, and a high susceptibility to pathogens, resulting in an irreversible process of tissue degeneration or quality degradation and eventual loss of commercial value, leading to economic loss. High quality fruits are a key guarantee for the healthy development of economic advantages. However, the understanding of postharvest conservation technology and the regulation of maturation, and senescence of pitaya are lacking. To better understand the means of postharvest storage of pitaya, extend the shelf life of pitaya fruit and prospect the postharvest storage technology, this paper analyzes and compares the postharvest quality changes of pitaya fruit, preservation technology, and senescence regulation mechanisms. This study provides research directions for the development of postharvest storage and preservation technology.

Fbw7 Inhibits the Progression of Activated B-Cell Like Diffuse Large B-Cell Lymphoma by Targeting the Positive Feedback Loop of the LDHA/lactate/miR-223 Axis.

Background: F-box and WD repeat domain-containing 7 (Fbw7) is well known as a tumor suppressor and ubiquitin ligase which targets a variety of oncogenic proteins for proteolysis. We previously reported that Fbw7 promotes apoptosis in diffuse large B-cell lymphoma (DLBCL) through Fbw7-mediated ubiquitination of Stat3. This study aimed to identify the mechanism of Fbw7-mediated aerobic glycolysis reprogramming in DLBCL. Methods: Expression levels of Fbw7 and Lactate Dehydrogenase A (LDHA) in human DLBCL samples were evaluated by immunohistochemistry. Crosstalk between Fbw7 and LDHA signaling was analyzed by co-immunoprecipitation, ubiquitination assay, western blotting and mRNA quanlitative analyses. In vitro and in vivo experiments were used to assess the effect of the Fbw7-mediated LDHA/lactate/miR-223 axis on DLBCL cells growth. Results: Fbw7 could interact with LDHA to trigger its ubiquitination and degradation. Inversely, lactate negatively regulated Fbw7 via trigging the expression of miR-223, which targeted Fbw7 3'-UTR to inhibit its expression. In vivo and in vitro experiments revealed that miR-223 promoted tumor growth and that the effects of miR-223 on tumor growth were primarily related to the inhibition of Fbw7-mediated LDHA's ubiquitination. Conclusions: We demonstrated that the ubiquitin-ligase Fbw7 played a key role in LDHA-related aerobic glycolysis reprogramming in DLBCL. Our study uncovers a negative functional loop consisting of a Fbw7-mediated LDHA/lactate/miR-223 axis, which may support the future ABC-DLBCL therapy by targeting LDHA-related inhibition.

Maintenance of Postharvest Quality and Reactive Oxygen Species Homeostasis of Pitaya Fruit by Essential Oil p-Anisaldehyde Treatment.

The performance of p-Anisaldehyde (PAA) for preserving pitaya fruit quality and the underpinning regulatory mechanism were investigated in this study. Results showed that PAA treatment significantly reduced fruit decay, weight loss and loss of firmness, and maintained higher content of total soluble solids, betacyanins, betaxanthins, total phenolics and flavonoids in postharvest pitaya fruits. Compared with control, the increase in hydrogen peroxide (H2O2) content and superoxide anion (O2•-) production was inhibited in fruit treated with PAA. Meanwhile, PAA significantly improved the activity of antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT). Moreover, PAA-treated pitaya fruit maintained higher ascorbic acid (AsA) and reduced-glutathione (GSH) content but lower dehydroascorbate (DHA) and oxidized glutathione (GSSG) content, thus sustaining higher ratio of AsA/DHA and GSH/GSSG. In addition, activities of ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and dehydrogenation ascorbic acid reductase (DHAR), as well as the expression of HpSOD, HpPOD, HpCAT, HpAPX, HpGR, HpDHAR and HpMDHAR, were enhanced after PAA treatment. The findings suggest that postharvest application of PAA may be a reliable method to control postharvest decay and preserve quality of harvested pitaya fruit by enhancing the antioxidant potential of the AsA-GSH cycle and activating an antioxidant defense system to alleviate reactive oxygen species (ROS) accumulation.

Decreased TMEM40 expression is associated with malignant behavior of cutaneous squamous cell carcinoma and inhibits tumor progression.

Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer in humans worldwide. The identification and characterization of cancer-associated transmembrane proteins are important for understanding the molecular biology of CSCC. The aim of the present study was to evaluate the expression pattern of transmembrane protein 40 (TMEM40) in CSCC and its clinical significance. The underlying mechanisms were also examined. Reverse transcription-quantitative PCR, western blot and immunohistochemistry analysis were used to determine the relative expression of TMEM40 in CSCC cell lines and clinical tissue samples. The effect of TMEM40 gene silencing on cell proliferation was also evaluated using Cell Counting Kit-8 assays. Wound healing assays, flow cytometry and Transwell assays were used to explore the migration, cell cycle distribution/apoptosis and invasion of CSCC cells following TMEM40 silencing, respectively. In the present study, increased TMEM40 expression was observed in CSCC tissue samples, compared with normal skin, and TMEM40 expression was associated with large tumor size in patients with CSCC. In vitro functional assays indicated that TMEM40 was involved in the regulation of A431 and SCL1 cell growth through its effects on the cell cycle and apoptosis. Silencing TMEM40 in A431 and SCL1 cells resulted in cell cycle arrest at the G0/G1 phase and promoted apoptosis. In addition, migration and invasion were significantly inhibited following silencing of TMEM40 expression in CSCC cells. Taken together, the results of the present study indicated that reduced TMEM40 expression could inhibit CSCC development and that TMEM40 may represent a therapeutic target in CSCC.

Handgrip Strength-Related Factors Affecting Health Outcomes in Young Adults: Association with Cardiorespiratory Fitness.

OBJECTIVES: Handgrip strength (HS) is a risk factor of all-cause mortality and cardiovascular diseases. However, the influencing factors and mechanisms contributing to this correlation remain unclear. Therefore, we aimed to explore factors related to HS and investigated the mechanism underlying its risk predictive value. METHODS: This was a prospective, cross-sectional study. One hundred forty-five participants were recruited from December 2019 to November 2020. HS was measured using a hydraulic hand dynamometer and adjusted for body mass index (HSBMI) and body surface area (HSBSA). Body composition was assessed via bioimpedance spectroscopy. Physical fitness was measured using a cardiopulmonary exercise test system. Univariate, multiple linear regression analyses and receiver operator characteristic curve (ROC) were conducted to evaluate the associations between various participant characteristics and HS. RESULTS: The average participant age was 21.68 ± 2.61 years (42.8% were male). We found positive correlations between HSBMI/HSBSA and VO2max, VEmax, Loadmax, and METmax in both sexes (p < 0.05). Lean-tissue, protein, total water, and inorganic salt percentages were positively correlated, and fat percentage was negatively correlated with HSBMI in men and with HSBMI and HSBSA in women (p < 0.05). Multiple regression revealed that VO2max was independently associated with HSBSA in both sexes (ß = 0.215, 0.173; 95%confidence interval [CI] = 0.032 - 0.398, 0.026-0.321; p = 0.022, 0.022, respectively) and independently associated with HSBMI in women (ß = 0.016, 95%CI = 0.004 - 0.029, p = 0.011). ROC analysis showed that HSBMI and HSBSA can moderately identify normal VO2max in men (area under curve [AUC] = 0.754, 0.769; p = 0.002, 0.001, respectively) and marginally identify normal VO2max in women (AUC = 0.643, 0.635; p = 0.029, 0.042, respectively). CONCLUSIONS: BMI- and BSA-adjusted HS could serve as indicators of physical health, and HSBSA may moderately reflect cardiorespiratory fitness levels in healthy young adults, particularly in males. Clinical trials registry site and number: China Clinical Trial Center (ChiCTR1900028228).

Prognostic value of delta-like protein 3 combined with thyroid transcription factor-1 in small-cell lung cancer.

Rovalpituzumab tesirine is a promising delta-like protein 3 (DLL3)-targeted antibody-drug conjugate for the treatment of small-cell lung cancer (SCLC). Thyroid transcription factor-1 (TTF-1) and DLL3 protein are associated with SCLC, and may be used to identify patients, who respond to the DLL3-targeted therapy. However, little is known about the expression pattern of the DLL3 protein, and the prognostic value of DLL3 and TTF-1 for SCLC. A total of 335 patients with SCLC were identified, including 11 patients with paired biopsy of primary site and lobectomy specimens, and 37 patients with paired specimens of primary and metastatic site. The DLL3 expression levels of individuals were evaluated using the anti-DLL3 antibody. No differences in DLL3 expression levels were observed in paired biopsy and lobectomy specimens (P=0.774), and paired primary and metastatic sites (P=0.472). SCLC cases with high DLL3 expression levels were more frequent in male patients (P=0.041), smokers (P=0.023) and patients with positive TTF-1 expression (P=0.006) compared with DLL3-low SCLC. DLL3-high SCLC exhibited worse overall survival compared with DLL3-low SCLC (log-rank test, P=0.007). Patients with TTF-1+ SCLC experienced a significantly worse overall survival compared with patients with TTF-1- SCLC (P<0.001). DLL3-low/TTF-1- was defined as a distinct molecular subgroup of SCLC with optimal prognosis (P<0.001). DLL3-low/TTF-1- was an independent prognostic marker for SCLC (P=0.001). In conclusion, the present study, to the best of our knowledge, provided novel evidence for SCLC intratumoral and intertumoral homogeneity with the identification of DLL3 protein levels. Therefore, it is reliable to use biopsy specimens to evaluate DLL3 expression levels for identification of patients who may benefit from DLL3-targeted therapy. In addition, DLL3 and TTF-1 are two protein markers with potential clinical value in risk stratification for patients with SCLC.

Diagnostic and prognostic factors for patients with primary pulmonary non-Hodgkin's lymphoma: A 16-year single-center retrospective study.

Primary pulmonary non-Hodgkin's lymphoma (PP-NHL) is a rare entity with non-specific symptoms and radiographic findings, as well as a difficult preoperative diagnosis. A limited number of studies have described PP-NHL in Chinese patients. The goal of the present study was to improve early diagnosis by examining prognostic factors in patients with PP-NHL. Therefore, a total of 29 patients with PP-NHL were included in the study between January 2001 and June 2017, including 14 with aggressive-type and 15 with indolent-type lymphomas (10 male, 19 female; median age, 50.3 years; range, 19-87 years). Pulmonary nodules and masses (55.2%) were the most common radiographic features. The diagnostic yield was 80% (12/15) by endobronchial biopsy or transbronchial lung biopsy and 100% by computed tomography (CT)-guided percutaneous needle lung biopsy (11/11) or surgery (8/8). Elevated lactate dehydrogenase levels and systemic symptoms were observed considerably more often in patients with aggressive disease than in those with indolent disease. The 1-, 3- and 5-year overall survival (OS) rates were 42, 32, and 21%, respectively, for all patients, 72, 57 and 43%, respectively, for patients with indolent lymphomas, and 13, 6 and 0%, respectively, for patients with aggressive lymphomas. The median OS rate for all patients was 12.0 months; however, the OS rate for patients with aggressive lymphomas was significantly shorter compared with those with indolent lymphomas (7.1 months vs. 16.6 months; P=0.002). Aggressive vs. indolent lymphoma status was indicated to be an independent prognostic factor for poor 5-year OS rate (hazard ratio, 5.98; P=0.014). In conclusion, bronchoscopic and CT-guided percutaneous needle lung biopsies were the most useful and least invasive procedures for diagnosing PP-NHL. Furthermore, aggressive PP-NHL was highly associated with poor 5-year OS rate and a poor prognosis.

Pitaya HpWRKY3 Is Associated with Fruit Sugar Accumulation by Transcriptionally Modulating Sucrose Metabolic Genes HpINV2 and HpSuSy1.

Sugar level is an important determinant of fruit taste and consumer preferences. However, upstream regulators that control sugar accumulation during fruit maturation are poorly understood. In the present work, we found that glucose is the main sugar in mature pitaya (Hylocereus) fruit, followed by fructose and sucrose. Expression levels of two sucrose-hydrolyzing enzyme genes HpINV2 and HpSuSy1 obviously increased during fruit maturation, which were correlated well with the elevated accumulation of glucose and fructose. A WRKY transcription factor HpWRKY3 was further identified as the putative binding protein of the HpINV2 and HpSuSy1 promoters by yeast one-hybrid and gel mobility shift assays. HpWRKY3 was localized exclusively in the nucleus and possessed trans-activation ability. HpWRKY3 exhibited the similar expression pattern with HpINV2 and HpSuSy1. Finally, transient expression assays in tobacco leaves showed that HpWRKY3 activated the expressions of HpINV2 and HpSuSy1. Taken together, we propose that HpWRKY3 is associated with pitaya fruit sugar accumulation by activating the transcriptions of sucrose metabolic genes. Our findings thus shed light on the transcriptional mechanism that regulates the sugar accumulation during pitaya fruit quality formation.

Correction: MYC Expression in Concert With BCL2 and BCL6 Expression Predicts Outcome in Chinese Patients With Diffuse Large B-Cell Lymphoma, Not Otherwise Specified.

[This corrects the article DOI: 10.1371/journal.pone.0104068.].

Acquired hypophosphatemic osteomalacia is easily misdiagnosed or neglected by rheumatologists: A report of 9 cases.

The aim of the present study was to assist rheumatologists in differentiating hypophosphatemic osteomalacia (HO) from mimic rheumatology diseases. Clinical data was obtained from 9 patients with acquired HO, initially misdiagnosed as mimic rheumatologic diseases. The data were retrospectively analyzed and a literature review was performed. The etiology of the cases was as follows: Adefovir dipivoxil-induced Fanconi syndrome was present in 6 of the cases, 2 were tumors and 1 case was chronic nephropathy. The chief complaint was thoracic or back pain and arthralgia, followed by progressive muscle weakness and dramatic movement limitation. All patients were transferred to 3-6 hospitals for extended periods due to misdiagnosis with conditions such as ankylosing spondylitis, chronic arthritis, lumbar disc disease, osteoporosis and somatoform disorder. Hypophosphatemia was observed in the patients and bone scans revealed diffusely decreased tracer uptake, with multiple hot spots of fractured sites and involved joints. Furthermore, patients' bone density was markedly low compared with the normal range for their age and sex. In the present study, 6 of the patients recovered when adefovir dipivoxil was stopped. In 1 case, hypophosphatemia was ameliorated following tumor resection. The remaining patients, 1 with sub-skull tumor and 1 with chronic kidney disease, had poor prognoses due to incurable diseases. In conclusion, diagnosing HO is challenging for rheumatologists and physicians. Basic examinations of electrolyte balance and bone mineral density should be performed, as should tumor screening and a careful collection of patient medical history and drugs in young patients with unexplained thoracic or back pain and muscle weakness. Removing any secondary etiology, such as drugs may dramatically improve the patients clinical manifestations and result in an improved prognosis.

A comprehensive review of uncommon EGFR mutations in patients with non-small cell lung cancer.

INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous group exhibiting differential responses to EGFR inhibitors. This retrospective study reviews the prevalence of uncommon EGFR mutations in a Chinese NSCLC cohort and the clinical characteristics and efficacy of EGFR tyrosine kinase inhibitors (TKIs) associated with these patients. MATERIALS ANDMETHODS: A total of 5363 lung cancer patients were screened and underwent EGFR genotyping at the Guangdong Lung Cancer Institute. Of those with uncommon EGFR mutations, the clinical characteristics and responses to EGFR-TKIs were reviewed retrospectively. RESULTS: Uncommon EGFR mutations were observed in 218 patients, comprising 11.9% of all patients with documented EGFR mutations. More smokers (30.7% vs. 24.3%, P=0.039) and males (54.1% vs. 44.4%, P=0.007) were among the patients with uncommon mutations compared with common mutations. The most frequent uncommon mutations were exon 20 insertions (30.7%, n=67), followed by G719X mutations (21.1%, n=46) and compound L858R mutations (17.0%, n=37). Favorable efficacy was observed in patients harboring compound L858R or G719X mutations, with a median progression-free survival (PFS) of 15.2 (95% CI: 8.7-21.7) or 11.6 (95% CI: 3.6-19.6) months, respectively. The median PFS of those with the T790M mutation or an exon 20 insertion was 1.0 (95% CI: 0.0-2.2) and 3.0 (95% CI: 1.3-4.7) months, respectively. CONCLUSION: This study reviewed the prevalence of uncommon EGFR mutations and their sensitivity to EGFR-TKIs. Favorable responses were observed in patients with G719X and compound L858R mutations, indicating that they may benefit from EGFR-TKIs as a first-line therapy.

Diffuse large B cell lymphoma associated with chronic inflammation arising within atrial myxoma: aggressive histological features but indolent clinical behaviour.

AIMS: Primary cardiac lymphoma (PCL) is a rare neoplasm. PCL is fatal, unless it is diagnosed and treated early. Recently, a small number of cases of diffuse large B cell lymphoma (DLBCL) arising within atrial myxoma have been reported in immunocompetent patients and showed aggressive histological features but an indolent clinical behaviour. METHODS AND RESULTS: We present four unusual cases of Epstein-Barr virus (EBV)-positive DLBCL arising within atrial myxoma with detailed clinical, histological, immunophenotypical and genotypical features in immunocompetent patients, and review the literature for 11 similar cases. All the patients appeared to have morphological features of DLBCL, B lineage immunophenotype, high proliferative index and latency type III of EBV infection. They achieved complete tumour resection without chemotherapy or radiotherapy after surgery and were healthy at 3- and 7-month and 7- and 10-year follow-ups, respectively. CONCLUSIONS: We suggest that this lymphoma should be regarded as a unique DLBCL associated with chronic inflammation (DLBCL-CI) because of an indolent clinical behaviour to avoid excessive or unnecessary treatments. In addition, early accurate diagnosis and complete resection of this tumour are crucial for optimal patient outcome.

Involvement of WRKY Transcription Factors in Abscisic-Acid-Induced Cold Tolerance of Banana Fruit.

Phytohormone abscisic acid (ABA) and plant-specific WRKY transcription factors (TFs) have been implicated to play important roles in various stress responses. The involvement of WRKY TFs in ABA-mediated cold tolerance of economical fruits, such as banana fruit, however remains largely unknown. Here, we reported that ABA application could induce expressions of ABA biosynthesis-related genes MaNCED1 and MaNCED2, increase endogenous ABA contents, and thereby enhance cold tolerance in banana fruit. Four banana fruit WRKY TFs, designated as MaWRKY31, MaWRKY33, MaWRKY60, and MaWRKY71, were identified and characterized. All four of these MaWRKYs were nuclear-localized and displayed transactivation activities. Their expressions were induced by ABA treatment during cold storage. More importantly, the gel mobility shift assay and transient expression analysis revealed that MaWRKY31, MaWRKY33, MaWRKY60, and MaWRKY71 directly bound to the W-box elements in MaNCED1 and MaNCED2 promoters and activated their expressions. Taken together, our findings demonstrate that banana fruit WRKY TFs are involved in ABA-induced cold tolerance by, at least in part, increasing ABA levels via directly activating NECD expressions.

18F-FDG PET/CT and contrast-enhanced CT findings of pulmonary cryptococcosis.

PURPOSE: Pulmonary cryptococcosis is an uncommon cause of pulmonary nodules in non-AIDS patients. This study reports the 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) and contrast-enhanced CT (CE-CT) findings of 42 patients with pulmonary cryptococcosis. MATERIALS AND METHODS: A retrospective review of the 18F-FDG PET/CT and CE-CT findings of 42 patients with histologically proven pulmonary cryptococcosis was conducted. All patients underwent PET/CT and CE-CT in the same session. The CT diagnosis was based on the location, morphological features, and enhancement of lesions. The PET/CT findings were recorded, and clinical data and surgical and histopathological findings were collected. RESULTS: The results of the PET scans revealed that 37 (88%) of 42 patients showed higher FDG uptake, and 5 (12%) patients demonstrated lower FDG uptake than the mediastinal blood pool. The maximum standardized uptake value (SUV) of pulmonary cryptococcosis ranged from 1.4 to 13.0 (average: 5.7±3.3, median 4.9). A single nodular pattern was the most prevalent pattern observed and was found in 29 (69%) patients. This pattern was followed by scattered nodular (n=4, 10%), clustered nodular (n=3, 7%), mass-like (n=3, 7%), and bronchopneumonic (n=3, 7%) patterns. The most frequent pattern of immunocompetent patients was the single nodular pattern (29 of 33, 88%). Immunocompromised patients most frequently pattern exhibited mass-like (3 of 9, 33%) and bronchopneumonic (3 of 9, 33%) patterns. CONCLUSION: Pulmonary cryptococcosis most commonly appears as single nodules in immunocompetent patients. Mass-like and bronchopneumonic patterns were common in immunocompromised patients. In 88% of patients, lung lesions showed high FDG uptake, thus mimicking a possible malignant condition.

Fbw7 regulates apoptosis in activated B-cell like diffuse large B-cell lymphoma by targeting Stat3 for ubiquitylation and degradation.

BACKGROUND: The ubiquitin-ligase Fbw7 acts as a tumor suppressor, targeting lots of proto-oncogenes for proteolysis. However, the exact role of Fbw7 in diffuse large B-cell lymphoma (DLBCL) development remains unclear. METHODS: We evaluated Fbw7 expression in patient samples of DLBCL using immunohistochemical staining. The effect of Fbw7 overexpression on cell viability and apoptosis was investigated using activated B-cell (ABC) like DLBCL cell lines. The mechanism of Fbw7 activity in DLBCL was investigated using immunoprecipitation, ubiquitination, western blot and qualitative analyses. RESULTS: The non-germinal center B-cell-like subtype of DLBCL showed reduced Fbw7 expression compared with the germinal center B-cell (GBC) subtype, and low Fbw7 expression was associated with a worse prognosis. Fbw7 overexpression caused decreased cell viability and increased apoptosis rates in the ABC-DLBCL cell lines SU-DHL-2 and OCI-LY-3. Importantly, Stat3 and phospho-Stat3Tyr705 stability were reduced following Fbw7 overexpression in ABC-DLBCL cell lines. In HEK293T and SU-DHL-2 cells, we demonstrated that Fbw7 interacts with Stat3 and pStat3Tyr705 to regulate their ubiquitylation and degradation. Downstream anti-apoptotic target genes of activated Stat3, including Myc, Survivin, Mcl-1, Pim-1, Bcl-2 and Bcl-xl showed decreased mRNA expression following exogenous Fbw7 overexpression. The negative relationship between Fbw7 and pStat3Tyr705 levels was also confirmed in DLBCL patient samples. CONCLUSION: The ubiquitin-ligase Fbw7 mediates apoptosis through targeting Stat3 for ubiquitylation and degradation in ABC-DLBCL. Thus, our study may offer a promising approach for ABC-DLBCL therapy through Stat3 inhibition.

Intravascular NK/T-cell lymphoma: a series of four cases.

Intravascular natural killer/T-cell lymphoma (IVNKTL) is a rare disorder and is reported gradually increased recently. We presented four cases including two extremely rare cases of primary lung IVNKTL with detailed clinicopathological features, therapy and prognosis, and reviewed the literature for 25 similar cases. H&E, Immunohistochemical staining and in situ hybridization (ISH) were used in the study. The medium-sized lymphoid cells were characterized by the selective growth within the kumina of vessels, particularly capillaries. The endothelial cells in the vessels exhibited positive CD34 staining. The lymphoid cells were positive for NK/T-cell markers, and cytotoxic proteins, and negative for B-cell markers. ISH demonstrated that the lymphoid cells expressed EBER. All the patients died of the disease a few months later. To conclude, the overall survival of patients with IVNKTL is very poor and the 1-year survival rate is only 31%. Patients with B symptoms and multiple organs involvement may be associated with the poor clinical prognosis. We deduce that the traditional chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is inadequate for the treatment of IVNKTL. Early accurate diagnosis by biopsy for this lymphoma may be crucial for the patients' medical prognosis due to the fatal disease course.

Overexpression of SRC-3 promotes esophageal squamous cell carcinoma aggressiveness by enhancing cell growth and invasiveness.

Steroid receptor coactivator-3 (SRC-3), a transcriptional coactivator for nuclear receptors and other transcription factors, plays an important role in the genesis and progression of several cancers. However, studies investigated the role of SRC-3 in esophageal squamous cell carcinomas (ESCCs) are limited, and the role of SRC-3 in tumor progression remains unclear. We examined the expression of SRC-3 in 8 ESCC cell lines and 302 human ESCC tissues by qPCR, Western blot, and immunohistochemistry. In addition, ESCC cell lines were subjected to proliferation and invasion assays, tumorigenicity assay, flow cytometry assay, qPCR, Western blot, and Chromatin Immunoprecipitation assay to investigate the role of SRC-3 in cancer progression. SRC-3 was overexpressed in 48% of cases and correlated with poor overall (P = 0.0076) and progression-free (P = 0.0069) survival of surgically resected ESCC patient. Cox regression analysis revealed that SRC-3 is an independent prognostic marker. Furthermore, we found that activation of insulin-like growth factor (IGF)/AKT) was involved in the SRC-3 on the cell growth and invasiveness in two ESCC cell lines, Eca109 and EC18 cells. SRC-3 overexpression is clinically and functionally relevant to the progression of human ESCC, and might be a useful molecular target for ESCC prognosis and treatment.