Nicotinamide N-Methyltransferase (NNMT) is Involved in Gastric Adenocarcinoma Immune Infiltration by Driving Amino Acid Metabolism.

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

Prediction of the Number of Cumulative Pulses Based on the Photon Statistical Entropy Evaluation in Photon-Counting LiDAR.

Photon-counting LiDAR encounters interference from background noise in remote target detection, and the statistical detection of the accumulation of multiple pulses is necessary to eliminate the uncertainty of responses from the Geiger-mode avalanche photodiode (Gm-APD). The cumulative number of statistical detections is difficult to select due to the lack of effective evaluation of the influence of the background noise. In this work, a statistical detection signal evaluation method based on photon statistical entropy (PSE) is proposed by developing the detection process of the Gm-APD as an information transmission model. A prediction model for estimating the number of cumulative pulses required for high-accuracy ranging with the background noise is then established. The simulation analysis shows that the proposed PSE is more sensitive to the noise compared with the signal-to-noise ratio evaluation, and a minimum PSE exists to ensure all the range detections with background noise are close to the true range with a low and stable range error. The experiments demonstrate that the prediction model provides a reliable estimation of the number of required cumulative pulses in various noise conditions. With the estimated number of cumulative pulses, when the signal photons are less than 0.1 per pulse, the range accuracy of 4.1 cm and 5.3 cm are obtained under the background noise of 7.6 MHz and 5.1 MHz, respectively.

Nodal downstaging to ypN0 after neoadjuvant chemotherapy positively impacts on survival of cT4N+ GC/GEJ patients.

BACKGROUND: The prognostic value of histomorphologic regression in primary gastric and gastroesophageal cancers (GC/GEJ) has been previously established, however, the impact of lymph node (LN) regression on survival still remains unclear. METHODS: A prospectively maintained database was reviewed to identify cT4N+ gastric and gastroesophageal cancers (GC/GEJ) after NAC (neoadjuvant chemotherapy). Patients were categorized into two groups based on LN status: cN+/ypN0 (downstaged N0) and cN+/ypN+ (persistent N+), long-term survival were analyzed using Kaplan-Meier survival estimates. RESULTS: In total, 125 patients with cT4N+ GC/GEJ underwent NAC followed by surgery were enrolled. A total of 39 patients (31.2%) had cN+/ypN0 (ypN0) disease, 86 patients (68.8%) had cN+/ypN+ (ypN+) disease. Prognosis in ypN+ patients was significantly worse than those in ypN0 group for 3- and 5-year overall survival (OS) (p < 0.05). The 3-year OS was 83%, 44% in ypN0 and ypN+ group, respectively. The 5-year OS was 75%, 35% in ypN0 and ypN+ group, respectively. Multivariable analysis suggested that multivisceral resection (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.14-0.76, p = 0.009), and ypN+ (HR = 3.42, 95% CI: 1.15-10.13, p =0.027) were independent prognostic factors for OS. CONCLUSION: Nodal downstaging is an important hallmark representing the effectiveness of NAC for GC/GEJ, and it positively impacts on survival of these patients.

Tumor radiomics signature for artificial neural network-assisted detection of neck metastasis in patient with tongue cancer.

BACKGROUND AND PURPOSE: To determine the neck management of tongue cancer, this study attempted to construct an artificial neural network (ANN)-assisted model based on computed tomography (CT) radiomics of primary tumors to predict neck lymph node (LN) status in patients with tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: Three hundred thirteen patients with tongue SCC were retrospectively included and randomly divided into training (60%), validation (20%) and internally independent test (20%) sets. In total, 1673 feature values were extracted after the semiautomatic segmentation of primary tumors and set as input layers of a classical 3-layer ANN incorporated with or without clinical LN (cN) status after dimension reduction. The receiver operating characteristic (ROC) curve, accuracy (ACC), sensitivity (SEN), specificity (SPE), area under curve (AUC) and Net Reclassification Index (NRI), were used to evaluate and compare the models. RESULTS: Four models with different settings were constructed. The ACC, SEN, SPE and AUC reached 84.1%, 93.1%, 76.5% and 0.943 (95% confidence interval: 0.891-0.996, p<.001), respectively, in the test set. The NRI of models compared with radiologists reached 40% (p<.001). The occult nodal metastasis rate was reduced from 30.9% to a minimum of 12.7% in the T1-2 group. CONCLUSION: ANN-based models that incorporated CT radiomics of primary tumors with traditional LN evaluation were constructed and validated to more precisely predict neck LN metastasis in patients with tongue SCC than with naked eyes, especially in early-stage cancer.

A Modified Design of the Pectoralis Major Myocutaneous Flap for Reconstruction of Head and Neck Defect.

ABSTRACT: Even though the pectoralis major myocutaneous flap (PMMF) still has an important role in the free flaps ear, it is reported to have drawbacks such as the limited cephalad extension and high incidence of total or partial flap necrosis. Various modifications have been attempted to augment the limited cephalad extension and a stable blood supply.The aim of this study is to describe a modified design of the skin paddle and preparation of the PMMF, to achieve stable blood circulation and sufficient pedicle length. The priority skin paddle is the medial part for its stable blood supply, and the lateral margin should be adjusted as needed. During the harvesting, the lateral thoracic artery (LTA) is preserved to protect the perforating branches, and the anterior sheath of the rectus abdominis muscle is used as a suture margin to prevent damage of the thin muscle of the PMMF. The skin paddles in this study are larger than those previously reported. All of the 21 patients in our study, the skin paddles show complete survival with no partial necrosis of skin paddle, fistula, or wound dehiscence.It is worthwhile to consider and preserve the LTA as a major contributor to a lateral and distal PMMF. This study would be useful in future and preparation of the PMMF in head and neck reconstruction.

An Entropy-Based Anti-Noise Method for Reducing Ranging Error in Photon Counting Lidar.

Photon counting lidar for long-range detection faces the problem of declining ranging performance caused by background noise. Current anti-noise methods are not robust enough in the case of weak signal and strong background noise, resulting in poor ranging error. In this work, based on the characteristics of the uncertainty of echo signal and noise in photon counting lidar, an entropy-based anti-noise method is proposed to reduce the ranging error under high background noise. Firstly, the photon counting entropy, which is considered as the feature to distinguish signal from noise, is defined to quantify the uncertainty of fluctuation among photon events responding to the Geiger mode avalanche photodiode. Then, the photon counting entropy is combined with a windowing operation to enhance the difference between signal and noise, so as to mitigate the effect of background noise and estimate the time of flight of the laser pulses. Simulation and experimental analysis show that the proposed method improves the anti-noise performance well, and experimental results demonstrate that the proposed method effectively mitigates the effect of background noise to reduce ranging error despite high background noise.

Noncoding RNA miR-205-5p mediates osteoporosis pathogenesis and osteoblast differentiation by regulating RUNX2.

As a kind of noncoding RNAs, microRNAs (miRNAs) play important roles in disease pathogenesis by regulating gene expression. However, the molecular mechanism of miRNAs in osteoporosis remains largely unknown. In the present study, we aim to explore the genome-wide miRNAs expression profile and the regulatory mechanism of miR-205-5p in osteoporosis. A total of 72 differentially expressed miRNAs were identified in osteoporosis via microarray technology and bioinformatics analysis. We focused on one of the abnormally expressed miRNAs, miR-205-5p, which was previously unknown in osteoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that miR-205-5p was upregulated in osteoporosis samples and its expression was gradually decreased during osteogenic differentiation. Besides, miR-205-5p overexpression could inhibit the activity of osteoblast markers, including collagen, type I, α 1 (COL1A1) and alkaline phosphatase (ALP) while miR-205-5p inhibition showed the opposite results. Moreover, bioinformatics analysis identified the potential targets of miR-205-5p, including runt-related transcription factor 2 (RUNX2), SMAD1 and BCL6, etc. The dual-luciferase reporter assay confirmed RUNX2 was directly targeted by miR-205-5p. Furthermore, the rescue experiments showed that RUNX2 overexpression could significantly weaken the effect of miR-205-5p on osteoblast markers, indicating that miR-205-5p may inhibit osteogenic differentiation by targeting RUNX2.

Efficacy of surgery combined with postoperative 125 I interstitial brachytherapy for treatment of acinic cell carcinoma of the parotid gland in children and adolescents.

BACKGROUND: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution. PROCEDURE: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated. RESULTS: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred. CONCLUSIONS: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT.

Subcutaneous Injection of Hyaluronic Acid to Decrease Acute Skin Toxicity After Adjuvant Interstitial Brachytherapy in Parotid Gland Cancer Patients: A Nonrandomized Controlled Trial.

PURPOSE: The aim was to evaluate the safety and efficacy of subcutaneous injection of hyaluronic acid in decreasing acute skin toxicity after adjuvant interstitial brachytherapy in parotid gland cancer patients. MATERIALS AND METHODS: Patients with histologically proven parotid gland cancer who would be treated with adjuvant interstitial brachytherapy were included in this nonrandomized controlled trial. Participants were nonrandomly divided into the experimental group and control group. Participants in the experimental group received an injection of hyaluronic acid subcutaneously immediately after interstitial brachytherapy during the operation. Acute toxicity was evaluated in the first 2 months. RESULTS: Thirty consecutive participants were included from April to September 2018. Twenty participants were in the experimental group, and 10 were in the control group. The median volume of hyaluronic acid was 8 mL (range, 4 to 11 mL). In total, the incidence of acute skin toxicity was 40% (8 of 20 patients) and 100% (10 of 10 patients) in the experimental group and control group, respectively. The difference in the dose delivered to 90% of the target volume of the affected skin was significant between the pre-plan (mean, 36.93 Gy) and the actuarial quality verification (mean, 27.70 Gy) in the experimental group (P = .004). The difference in scoring of acute skin toxicity was significant between the experimental and control groups (P = .001). No clear correlation was found between the dose delivered to 90% of the target volume of the affected skin and the scoring of acute skin toxicity (P = .266). CONCLUSIONS: Subcutaneous injection of hyaluronic acid was safe and efficient in decreasing acute skin toxicity after adjuvant interstitial brachytherapy in parotid gland cancer patients according to the preliminary results.

Spore Germination as a Target for Antifungal Therapeutics.

Spores are required for long-term survival of many organisms, including most fungi. For the majority of fatal human fungal pathogens, spore germination is the key process required to initiate vegetative growth and ultimately cause disease. Because germination is required for pathogenesis, the process could hold fungal-specific targets for new antifungal drug development. Compounds that inhibit germination could be developed into high efficacy, low-toxicity drugs for use in the prevention and/or treatment of fungal spore-mediated diseases. To identify drugs with the ability to inhibit pathogenic fungal spore germination, we developed a novel luciferase-based germination assay, using spores of the meningitis-causing yeast Cryptococcus. We screened the L1300 Selleck Library of FDA-approved drugs and identified 27 that inhibit germination. Of these, 22 inhibited both germination and yeast growth, and 21 have not been previously indicated for use in the treatment of fungal diseases. We quantitated the inhibition phenotypes of 10 specific germination/growth inhibitors in detail and tested one drug, the antiparasitic compound pentamidine, in our mouse intranasal model of cryptococcal infection. We discovered that pentamidine was effective at reducing lung fungal burdens when used in either prophylaxis (before infection) or treatment (after establishing an infection). Due to its efficacy in vivo and low intranasal toxicity, pentamidine is a lead candidate for repurposing for broader use as an antigerminant to prevent spore-mediated disease in immunocompromised patients. Not only does pentamidine provide an opportunity for prophylaxis against fungal spores, but it also provides proof of concept for targeting pathogenic spore germination for antifungal drug development.

Definitive 125I Brachytherapy of Locally Advanced Adenoid Cystic Carcinoma Involving the Skull Base With Satisfying Efficacy and Safety.

PURPOSE: Adenoid cystic carcinoma (ACC) involving the skull base is difficult to treat and sometimes unresectable. The purpose of this study was to evaluate the efficacy and safety of 125I radioactive seed interstitial brachytherapy for treatment of these patients. MATERIALS AND METHODS: Patients with ACC involving the skull base treated by definitive 125I brachytherapy from March 2008 through December 2018 at the Peking University Hospital of Stomatology (Beijing, China) were retrospectively identified. Overall survival (OS), as the primary efficacy indicator, and progression-free survival (PFS) and distant metastasis-free survival (DFS), as the secondary efficacy indicators, were analyzed by Kaplan-Meier survival analysis and Cox regression analysis. Adverse radiotherapy (RT) reactions, as safety indicators, were recorded. RESULTS: Thirty-two patients with (r)T4b locally advanced disease were enrolled. The prescription dose (PD) was 60 to 120 Gy. The dose delivered to 90% of the target volume was 99.1 to 145.2 Gy, the percentage of the target volume receiving at least 100% of the PD was at least 88.2%, and the percentage of the target volume receiving at least 150% of the PD was smaller than 74.0%. Mean follow-up was 32 months (median, 21 months; range, 3 to 95 months). The 1- and 3-year OS rates were 93.3 and 62.6%, the 1- and 3-year PFS rates were 90.0 and 46.4%, and the 1- and 3-year DFS rates were 91.7 and 61.1%, respectively. Survival was significantly associated with local recurrence (P = .04) and distant metastasis except in the lung (P = .05). The rate of severe chronic adverse RT reactions was 3.1%; no severe acute adverse RT reactions were observed. CONCLUSION: 125I brachytherapy appears to be an effective and safe treatment in the short-term for ACC involving the skull base and could be the preferred treatment for patients with prior RT. Local control with brachytherapy could provide survival benefit even in patients with lung metastasis.

Inhaled Cryptococcus neoformans elicits allergic airway inflammation independent of Nuclear Factor Kappa B signalling in lung epithelial cells.

Pulmonary challenge with the ubiquitous fungus Cryptococcus neoformans results in allergic airway inflammation (AAI) characterized by robust recruitment of eosinophils and T cells producing type 2 cytokines to the lungs. Previous studies have demonstrated a critical role for Nuclear Factor Kappa B (NF-κB) activation within lung epithelial cells (LECs) in driving AAI in response to protein allergens, yet the role of LEC-intrinsic NF-κB in promoting AAI following exposure to C. neoformans is poorly understood. To investigate the role of LEC-intrinsic NF-κB in promoting AAI following C. neoformans challenge, we used IKK∆LEC mice, which lack canonical NF-κB activation specifically within LECs. IKK∆LEC and littermate control mice were intranasally challenged with 106 CFU of C. neoformans strain 52D, and lung tissues were collected at 7, 14 and 21 days post infection to assess the development of AAI. Notably, the absence of epithelial NF-κB signalling did not affect the magnitude or kinetics of lung eosinophilia when compared with the response in wild-type control mice. The total numbers of lung T cells producing the type 2 cytokines interleukin-5 and interleukin-13 were also unchanged in IKK∆LEC mice. Furthermore, IKK∆LEC mice showed no defect in the recruitment of protective interferon-γ-producing CD4 T cells to the lungs, fungal clearance, or host survival compared with control mice. Immunofluorescence imaging surprisingly revealed no evidence of nuclear localization of NF-κB in LECs in response to C. neoformans challenge, indicating that NF-κB is not activated within these cells. Taken together, these data strongly suggest that NF-κB signalling within LECs does not promote AAI observed in response to C. neoformans.

Mandibular growth in survivors of pediatric parotid gland carcinoma treated with interstitial brachytherapy.

BACKGROUND: The aim of the study was to present long-term results of mandibular growth in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. PROCEDURE: Twenty-five survivors of pediatric parotid gland carcinoma treated with iodine-125 seed interstitial brachytherapy were included for quantitative analysis, including three dimensional (3D) cephalometry and measurement of mandibular volume. RESULTS: 3D cephalometry showed that the median fore-and-aft increments of the lengths of the condyle, the ramus, and the body of the mandible were 1.23, 0.19, and 1.66 mm for the affected side, respectively, and were 1.37, 1.95, and 3.42 mm for the unaffected side, respectively. The difference in increments of the ramus was statistically significant between the affected side and the unaffected side (P = 0.003; P < 0.05). Moreover, mandibular volume measurements showed that the median fore-and-aft increments of the volumes of the condyle, the ramus, and the body of the mandible were 290.62, 220.14, and 1706.40 mm3 for the affected side, respectively, and were 269.15, 370.40, and 1469.86 mm3 for the unaffected side, respectively. The difference in increments was statistically significant between the affected side and the unaffected side for the ramus (P = 0.005; P < 0.05) and the body (P = 0.043; P < .05). CONCLUSION: Mandibular growth was affected by interstitial brachytherapy, especially for the ramus, in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. Nevertheless, the impact was mild in these survivors.

Cystadenoma of Minor Salivary Gland With Cervical Metastasis: Benign or Malignant?

A cystadenoma originating in the salivary gland is a rare neoplasm that can originate from the major or minor salivary glands. Although this tumor has the potential to recur if it is incompletely excised, it has been regarded as a benign tumor because it has not been determined to be associated with local tissue destruction or metastasis. This report serves as an update to the current understanding of cystadenoma. The patient in this case study presented with a recurrent painless mass in her left retromolar and submandibular regions that had persisted for more than 2 years. Histologic analysis showed that this lesion was a recurrent cystadenoma of the minor salivary gland, with cervical lymph nodes testing positive for tumor cells. After more than 3 years of clinical follow-up, no signs of recurrence were observed. A case of cystadenoma with cervical metastasis is presented; further attention should be paid to patients with recurrent cystadenoma that also might contain lymph node metastasis.

Protein Composition of Infectious Spores Reveals Novel Sexual Development and Germination Factors in Cryptococcus.

Spores are an essential cell type required for long-term survival across diverse organisms in the tree of life and are a hallmark of fungal reproduction, persistence, and dispersal. Among human fungal pathogens, spores are presumed infectious particles, but relatively little is known about this robust cell type. Here we used the meningitis-causing fungus Cryptococcus neoformans to determine the roles of spore-resident proteins in spore biology. Using highly sensitive nanoscale liquid chromatography/mass spectrometry, we compared the proteomes of spores and vegetative cells (yeast) and identified eighteen proteins specifically enriched in spores. The genes encoding these proteins were deleted, and the resulting strains were evaluated for discernable phenotypes. We hypothesized that spore-enriched proteins would be preferentially involved in spore-specific processes such as dormancy, stress resistance, and germination. Surprisingly, however, the majority of the mutants harbored defects in sexual development, the process by which spores are formed. One mutant in the cohort was defective in the spore-specific process of germination, showing a delay specifically in the initiation of vegetative growth. Thus, by using this in-depth proteomics approach as a screening tool for cell type-specific proteins and combining it with molecular genetics, we successfully identified the first germination factor in C. neoformans. We also identified numerous proteins with previously unknown functions in both sexual development and spore composition. Our findings provide the first insights into the basic protein components of infectious spores and reveal unexpected molecular connections between infectious particle production and spore composition in a pathogenic eukaryote.

A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens.

Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of Candida and Cryptococcus, reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of Aspergillus, including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies.

Sporulation: how to survive on planet Earth (and beyond).

Sporulation is a strategy widely utilized by a wide variety of organisms to adapt to changes in their individual environmental niches and survive in time and/or space until they encounter conditions acceptable for vegetative growth. The spores produced by bacteria have been the subjects of extensive studies, and several systems such as Bacillus subtilis have provided ample opportunities to understand the molecular basis of spore biogenesis and germination. In contrast, the spores of other microbes, such as fungi, are relatively poorly understood. Studies of sporulation in model systems such as Saccharomyces cerevisiae and Aspergillus nidulans have established a basis for investigating eukaryotic spores, but very little is known at the molecular level about how spores function. This is especially true among the spores of human fungal pathogens such as the most common cause of fatal fungal disease, Cryptococcus neoformans. Recent proteomic studies are helping to determine the molecular mechanisms by which pathogenic fungal spores are formed, persist and germinate into actively growing agents of human disease.

MicroRNA-1284 inhibits proliferation and induces apoptosis in SGC-7901 human gastric cancer cells.

OBJECTIVES: To explore the functional effects of miR-1284 on gastric cancer cells. RESULTS: Overexpression of miR-1284 significantly reduced SGC-7901 cell proliferation, but improved apoptosis. However, miR-1284 suppression displayed the inversed impacts. Furthermore, the protein levels of p27, Bax, procaspase-3 and active caspase-3 were up-regulated by miR-1284 overexpression, but were down-regulated by miR-1284 suppression. The level of Bcl-2 was down-regulated by miR-1284 overexpression, while it was up-regulated by miR-1284 suppression. The level of p21 was unaffected. CONCLUSION: These results suggest that miR-1284 overexpression might be a suppressor for gastric cancer via controlling of cell proliferation and apoptosis.

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia.

Cryptococcal meningoencephalitis is a fungal infection that predominantly affects immunocompromised patients and is uniformly fatal if left untreated. Timely diagnosis is difficult, and screening or prophylactic measures have generally not been successful. Thus, we need a better understanding of early, asymptomatic pathogenesis. Inhaled cryptococci must survive the host immune response, escape the lung, and persist within the bloodstream in order to reach and invade the brain. Here we took advantage of the zebrafish larval infection model to assess the process of cryptococcal infection and disease development sequentially in a single host. Using yeast or spores as infecting particles, we discovered that both cell types survived and replicated intracellularly and that both ultimately established a sustained, low-level fungemia. We propose that the establishment and maintenance of this sustained fungemia is an important stage of disease progression that has been difficult to study in other model systems. Our data suggest that sustained fungemia resulted from a pattern of repeated escape from, and reuptake by, macrophages, but endothelial cells were also seen to play a role as a niche for cryptococcal survival. Circulating yeast collected preferentially in the brain vasculature and eventually invaded the central nervous system (CNS). As suggested previously in a mouse model, we show here that neutrophils can play a valuable role in limiting the sustained fungemia, which can lead to meningoencephalitis. This early stage of pathogenesis-a balanced interaction between cryptococcal cells, macrophages, endothelial cells, and neutrophils-could represent a window for timely detection and intervention strategies for cryptococcal meningoencephalitis.