No abstract

Angiogenesis induced by tumor cells after implantation in the host begins at a very early stage, i.e., when the tumor mass contains roughly 100-300 cells. Identification of chemotactic signals that initiate tumor cell migration toward the existing vasculature may provide valuable targets for preventing tumor progression and/or metastases.

Summary Toll-Like Receptor (TLR) signaling is a key component of innate immunity. Aberrant TLR activation leads to immune disorders via dysregulation of cytokine production, such as IL-12/23. Herein we identify and characterize PIKfyve, a lipid kinase, as a critical player in TLR signaling using apilimod as an affinity tool. Apilimod is a potent small molecular inhibitor of IL-12/23 with an unknown target and has been evaluated in clinical trials for patients with Crohn’s disease or rheumatoid arthritis. Using a chemical genetics approach, we show that it binds to PIKfyve and blocks its phosphotransferase activity, leading to selective inhibition of IL-12/23p40. Pharmacological or genetic inactivation of PIKfyve is necessary and sufficient for suppression of IL-12/23p40 expression. Thus, we have uncovered a novel phosphoinositide-mediated regulatory mechanism that controls TLR signaling.

Summary Candida albicans is a major fungal pathogen of humans, causing both superficial and life‐threatening systemic infections in immunocompromised people. The conserved Ras/cAMP/PKA pathway plays a key role in regulating multiple traits important for the virulence of C. albicans such as cell growth, yeast‐hyphal transition, white‐opaque switching, sexual reproduction and biofilm development. Diverse external signals influence cell physiology by activating this signaling pathway. The key components of the Ras/cAMP/PKA pathway include two Ras GTPases (Ras1 and Ras2), an adenylyl cyclase (Cyr1, also known as Cdc35), two cyclic nucleotide phosphodiesterases (Pde1 and Pde2) and the catalytic (Tpk1 and Tpk2) and regulatory (Bcy1) subunits of PKA kinase. Activation of this pathway dramatically alters the gene expression profile via several transcription factors, leading to the activation of specific biological processes. Here, we review the progress made in the past two decades to elucidate the molecular mechanisms by which the Ras/cAMP/PKA pathway senses diverse environmental cues and controls specific cellular responses and its connection with other signaling pathways in C. albicans.

Background The intranasal endoscopic prelacrimal recess approach (PLRA) access to all aspects of the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct and its use have been reported in the treatment of many maxillary sinus and lateral skull base diseases. Objective To retrospectively assess the effectiveness of a 10-year multicenter follow-up for the resection of inverted papilloma of the maxillary sinus (IPMS) via a PLRA. Methods A total of 71 patients were admitted and underwent IPMS excision via an intranasal endoscopic PLRA from 2003 to 2013. All patients underwent high-resolution computed tomography scanning of the nasal sinus, and some also underwent magnetic resonance imaging examination. Results Based on the Krouse staging system, all 71 patients belong to T3 staging. The PLRA was employed to remove IPMS in 71 patients. The postoperative pathological examination of the excised tissue revealed inverted papilloma, and cancerization was identified in 3 patients. The median follow-up time was 37.3 months (range: 13–134 months). Of the 71 patients, reoccurrence was seen in 5 patients (7.04%); 5 patients (7.04%) experienced numbness of the upper lid and the ala of the nose and 4 (5.63%) experienced mild collapse of the ala of the nose. Conclusions These multicenter follow-up results demonstrated that the PLRA is a safe and effective method for the excision of primary or recurrent IPMS with lower postoperative complications and recurrent rate.

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In this study, the content, structure, antityrosinase activity, and mechanism of longan bark condensed tannins were evaluated. The findings obtained from mass spectrometry demonstrated that longan bark condensed tannins were mixtures of procyanidins, propelargonidins, prodelphinidins, and their acyl derivatives (galloyl and p-hydroxybenzoate). The enzyme analysis indicated that these mixtures were efficient, reversible, and mixed (competitive is dominant) inhibitor of tyrosinase. What's more, the mixtures showed good inhibitions on proliferation, intracellular enzyme activity and melanogenesis of mouse melanoma cells (B). From molecular docking, the results showed the interactions between inhibitors and tyrosinase were driven by hydrogen bond, electrostatic, and hydrophobic interactions. In addition, high levels of total phenolic and extractable condensed tannins suggested that longan bark might be a good source of tyrosinase inhibitor. This study would offer theoretical basis for the development of longan bark condensed tannins as novel food preservatives and medicines of skin diseases.

T umors originating or involving the pterygopalatine fossa (PPF) or infratemporal fossa (ITF) of the maxilla are uncommon, comprising only 0.5% of all head and neck tumors.2 Before the era of endoscopic surgery, lateral rhinotomy, midfacial degloving, the CaldwellLuc operation, and even a transmaxillary approach had been proposed for the resection of tumors of the PPF, but these approaches always resulted in some form of morbidity, such as facial scarring. After the introduction of endoscopic techniques, many papers were published describing an endonasal endoscopic approach and its application. 1,6,[8][9][10][11] The transpterygoid approach is commonly used when accessing the lateral recess of the sphenoid, the PPF, or the ITF, but this approach is often accompanied by cauterization of the sphenopalatine and vidian arteries and vidian nerve section. If the lesion involves the lateral aspect of the pterygoid process, the inferior turbinate has to be sacrificed; in addition, the frontal process of the maxilla limits surgical freedom. We developed a novel surgical method called the prelacrimal recess approach (PLRA), which can lead us directly to the PPF and ITF after creation and medialization of a "lacrimal sac and inferior turbinate flap." aBBreViatiONS IMA = internal maxillary artery; ITF = infratemporal fossa; PLRA = prelacrimal recess approach; PPF = pterygopalatine fossa; TEM = transnasal endoscopic maxillectomy. OBJectiVe This study was undertaken to analyze the results of a novel surgical method-the endoscopic prelacrimal recess approach (PLRA)-in patients with tumors involving the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). The surgical technique and indications for this approach are also discussed. methOdS The authors analyzed data from 7 cases involving patients who underwent resection of PPF and ITF tumors by means of the endoscopic PLRA from 2004 to 2013. Preoperative and postoperative imaging studies were available in all cases and were reviewed. The surgical specimens were all confirmed to be schwannomas. reSultS All tumors were completely resected via endoscopic PLRA. There were no recurrences noted over a 28-month follow-up period. In 4 cases, the patients experienced postoperative facial numbness during the first two weeks after surgery, which gradually lessened thereafter. One patient continued to have mild facial numbness at most recent follow-up. The numbness had fully resolved in the other 3 cases. cONcluSiONS The intranasal endoscopic removal of schwannoma from PPF and ITF via PLRA can spare the whole lateral nasal wall, resulting in a reduction in morbidity. This is a novel minimally invasive surgical method for PPF and ITF tumors.