Nodular scalp mass as the first presentation of pulmonary large cell neuroendocrine carcinoma: a case report.

Metastasis of lung cancer to the skin is uncommon, presenting in 0.22% to 12% of lung cancer patients, and it is extremely rare for skin metastasis to be the first clinical manifestation of lung cancer. In the few cases where skin metastasis has been reported as the first sign of lung cancer, the patients were typically heavy smokers or had preexisting respiratory diseases and symptoms. This prompted clinicians to consider skin metastasis of a pulmonary malignancy. Large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer that accounts for approximately 3% of lung cancers. LCNEC mainly metastasizes to visceral organs, such as the liver, bone, and brain, and it only shows metastasis to the skin in very rare cases. Herein, we report an unusual case of a metastatic skin lesion as the first sign of primary pulmonary LCNEC, in a 63-year-old woman with no pulmonary symptoms or personal history of smoking or pulmonary disease.

Delayed-onset micrococcus luteus-induced postoperative endophthalmitis several months after cataract surgery: A case report.

BACKGROUND: Micrococcus luteus (M. luteus)-induced endophthalmitis is very rare and and may present as either acute or chronic postoperative endophthalmitis. The aim of this study was to report a case of delayed-onset M. luteus-induced endophthalmitis that occurred several months after cataract surgery. CASE SUMMARY: A 78-year-old man presented with decreased vision, pain and redness in the right eye that had begun 3 days prior. He had undergone cataract surgery 4 mo prior. Visual acuity was counting fingers; slit-lamp examination revealed conjunctival injection, posterior corneal precipitates, anterior chamber inflammation (cell 4+), and hypopyon. Fundus examination revealed moderate vitreous haze. Urgent vitrectomy was performed for suspected infectious endophthalmitis, followed by vitreous irrigation with injections of antibiotics. On the postoperative day 1, anterior chamber cell decreased to 2+ and hypopyon was not observed on slit lamp examination. Six days postoperatively, the patient had recurrent eye pain, and the anterior chamber cell grade increased to 4+; hypopyon recurred in the anterior chamber, and whitish plaque was observed in the lens capsule. Therefore, the patient underwent intraocular lens (IOL) and lens capsule removal, followed by vitreous irrigation, antibiotics injection, and vitrectomy. M. luteus was identified from a lens capsule culture. CONCLUSION: In cases of delayed-onset M. luteus-induced endophthalmitis, early vitrectomy and removal of the IOL and lens capsule may be necessary.

Superficial angiomyxoma of the posterior neck.

Superficial angiomyxoma (SA) is a rare, benign, cutaneous soft tissue tumor. It is composed of myxoid matrix and blood vessels. Herein, we report a case of a solitary SA on the posterior neck of a 6-year-old boy. An analysis of the biopsied specimen showed a prominent myxoid stroma with thin-walled, branching blood vessels, revealing the presence of an SA. SA especially that originating in the posterior neck, is rarely seen and should be considered as a differential diagnosis for a solitary mass in the posterior neck.

Schisandra Extract and Ascorbic Acid Synergistically Enhance Cognition in Mice Through Modulation of Mitochondrial Respiration.

Cognitive decline is observed in aging and neurodegenerative diseases, including Alzheimer's disease (AD) and dementia. Intracellular energy produced via mitochondrial respiration is used in the regulation of synaptic plasticity and structure, including dendritic spine length and density, as well as for the release of neurotrophic factors involved in learning and memory. To date, a few synthetic agents for improving mitochondrial function have been developed for overcoming cognitive impairment. However, no natural compounds that modulate synaptic plasticity by directly targeting mitochondria have been developed. Here, we demonstrate that a mixture of Schisandra chinensis extract (SCE) and ascorbic acid (AA) improved cognitive function and induced synaptic plasticity-regulating proteins by enhancing mitochondrial respiration. Treatment of embryonic mouse hippocampal mHippoE-14 cells with a 4:1 mixture of SCE and AA increased basal oxygen consumption rate. We found that mice injected with the SCE-AA mixture showed enhanced learning and memory and recognition ability. We further observed that injection of the SCE-AA mixture in mice significantly increased expression of postsynaptic density protein 95 (PSD95), an increase that was correlated with enhanced brain-derived neurotrophic factor (BDNF) expression. These results demonstrate that a mixture of SCE and AA improves mitochondrial function and memory, suggesting that this natural compound mixture could be used to alleviate AD and aging-associated memory decline.

Shedding light on complexity of protein-protein interactions in cancer.

Most cell signaling and surveillance circuits are physically maintained through a dense network of protein-protein interactions (PPIs). Genetic mutations, epigenetic changes as well as alterations in cellular microenvironment can markedly rewire the patterns of PPIs, which leads to neoplastic growth of cancer cells. There are accumulating evidences that drugs that target-specific PPI pairs may provide an opportunity to treat cancers with a higher specificity and efficacy than those inhibiting enzymatic activity of oncogenic proteins. Therefore, identification of driving PPIs in a given cancer not only improves our understanding for individual cancers, but it also provides therapeutic opportunities to cure the specific cancer. In this review, we introduce some examples of aberrant PPI complexes identified in several major types of cancers, and recent technical developments that permit assessment of PPI strength in clinical specimens. Finally, we discuss the potential use of such PPI profiling for the purpose of precision medicine.

Profiling of protein-protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors.

The accumulation of genetic and epigenetic alterations in cancer cells rewires cellular signalling pathways through changes in the patterns of protein-protein interactions (PPIs). Understanding these patterns may facilitate the design of tailored cancer therapies. Here, we show that single-molecule pull-down and co-immunoprecipitation techniques can be used to characterize signalling complexes of the human epidermal growth-factor receptor (HER) family in specific cancers. By analysing cancer-specific signalling phenotypes, including post-translational modifications and PPIs with downstream interactions, we found that activating mutations of the epidermal growth-factor receptor (EGFR) gene led to the formation of large protein complexes surrounding mutant EGFR proteins and to a reduction in the dependency of mutant EGFR signalling on phosphotyrosine residues, and that the strength of HER-family PPIs is correlated with the strength of the dependence of breast and lung adenocarcinoma cells on HER-family signalling pathways. Furthermore, using co-immunoprecipitation profiling to screen for EGFR-dependent cancers, we identified non-small-cell lung cancers that respond to an EGFR-targeted inhibitor. Our approach might help predict responses to targeted cancer therapies, particularly for cancers that lack actionable genomic mutations.

Real-time single-molecule coimmunoprecipitation of weak protein-protein interactions.

Coimmunoprecipitation (co-IP) analysis is a useful method for studying protein-protein interactions. It currently involves electrophoresis and western blotting, which are not optimized for detecting weak and transient interactions. In this protocol we describe an advanced version of co-IP analysis that uses real-time, single-molecule fluorescence imaging as its detection scheme. Bait proteins are pulled down onto the imaging plane of a total internal reflection (TIR) microscope. With unpurified cells or tissue extracts kept in reaction chambers, we observe single protein-protein interactions between the surface-immobilized bait and the fluorescent protein-labeled prey proteins in real time. Such direct recording provides an improvement of five orders of magnitude in the time resolution of co-IP analysis. With the single-molecule sensitivity and millisecond time resolution, which distinguish our method from other methods for measuring weak protein-protein interactions, it is possible to quantify the interaction kinetics and active fraction of native, unlabeled bait proteins. Real-time single-molecule co-IP analysis, which takes ∼4 h to complete from lysate preparation to kinetic analysis, provides a general avenue for revealing the rich kinetic picture of target protein-protein interactions, and it can be used, for example, to investigate the molecular lesions that drive individual cancers at the level of protein-protein interactions.

Real-time single-molecule co-immunoprecipitation analyses reveal cancer-specific Ras signalling dynamics.

Co-immunoprecipitation (co-IP) has become a standard technique, but its protein-band output provides only static, qualitative information about protein-protein interactions. Here we demonstrate a real-time single-molecule co-IP technique that generates real-time videos of individual protein-protein interactions as they occur in unpurified cell extracts. By analysing single Ras-Raf interactions with a 50-ms time resolution, we have observed transient intermediates of the protein-protein interaction and determined all the essential kinetic rates. Using this technique, we have quantified the active fraction of native Ras proteins in xenograft tumours, normal tissue and cancer cell lines. We demonstrate that the oncogenic Ras mutations selectively increase the active-Ras fraction by one order of magnitude, without affecting total Ras levels or single-molecule signalling kinetics. Our approach allows us to probe the previously hidden, dynamic aspects of weak protein-protein interactions. It also suggests a path forward towards precision molecular diagnostics at the protein-protein interaction level.

Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1.

In neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca2+ levels rise. However, in vitro reconstitution experiments have failed to recapitulate key characteristics of Ca2+-triggered membrane fusion. Using an in vitro single-vesicle fusion assay, we found that membrane-anchored Syt1 enhanced Ca2+ sensitivity and fusion speed. This stimulatory activity of membrane-anchored Syt1 dropped as the Ca2+ level rose beyond physiological levels. Thus, Syt1 requires the membrane anchor to stimulate vesicle fusion at physiological Ca2+ levels and may function as a dynamic presynaptic Ca2+ sensor to control the probability of neurotransmitter release.