Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.

The evolutionary path of the epithelial sodium channel δ-subunit in Cetartiodactyla points to a role in sodium sensing.

The epithelial sodium channel (ENaC) plays a key role in osmoregulation in tetrapod vertebrates and is a candidate receptor for salt taste sensation. There are four ENaC subunits (α, β, γ, δ) which form αβγ- or δβγ ENaCs. While αβγ-ENaC is a 'maintenance protein' controlling sodium and potassium homeostasis, δβγ-ENaC might represent a 'stress protein' monitoring high sodium concentrations.

Rare Superior and Middle Trunk Fusion Accompanied by Altered Division Rearrangement Results in a Unique Brachial Plexus Variant: A Case Report.

During routine dissections of cadavers as part of the medical curriculum, we identified a rare unilateral variation in the brachial plexus on the right side of a female body donor. This variation consisted of four unusual changes to the regular pattering of nerve bundles and the dorsal scapular artery permeating the complex neural network. The variation included contributions of root C4 to the plexus by a root C4/C5 anastomosis, a rare fusion of the superior and middle trunks to a 'superomiddle' trunk, a preliminary, proximal branching of the suprascapular nerve off the C5 root.

Sulforaphane Inhibits Adhesion and Migration of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro.

Only 20% of patients with muscle-invasive bladder carcinoma respond to cisplatin-based chemotherapy. Since the natural phytochemical sulforaphane (SFN) exhibits antitumor properties, its influence on the adhesive and migratory properties of cisplatin- and gemcitabine-sensitive and cisplatin- and gemcitabine-resistant RT4, RT112, T24, and TCCSUP bladder cancer cells was evaluated. Mechanisms behind the SFN influence were explored by assessing levels of the integrin adhesion receptors β1 (total and activated) and β4 and their functional relevance.

Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM) is a major risk factor for advanced liver disease. The aim of this prospective cohort study was to assess the prevalence and associated risk factors of liver fibrosis and cirrhosis in primary care centers participating in the diabetes disease management program (DMP) in Germany.

Methods: A total of 175 participants with the diagnosis of T2DM were enrolled in two primary care centers.

Human airway tuft cells influence the mucociliary clearance through cholinergic signalling.

Background: Airway tuft cells, formerly called brush cells have long been described only morphologically in human airways. More recent RNAseq studies described a chemosensory cell population, which includes tuft cells, by a distinct gene transcription signature. Yet, until which level in the tracheobronchial tree in native human airway epithelium tuft cells occur and if they function as regulators of innate immunity, e.

Aridanin and oleanane-3- O-β-D-glucoside-2'-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells.

Ethnopharmacological Relevance: Tetrapleura tetraptera (Schumach. and Thonn.) Taub.

Mistletoe Extracts from Different Host Trees Disparately Inhibit Bladder Cancer Cell Growth and Proliferation.

Extracts of European mistletoe () are popular as a complementary treatment for patients with many different cancer types. However, whether these extracts actually block bladder cancer progression remains unknown. The influence of different mistletoe extracts on bladder cancer cell growth and proliferation was investigated by exposing RT112, UMUC3, and TCCSup cells to mistletoe from hawthorn (), lime trees (), willow trees (), or poplar trees ().

Cucumis sativus (Cucurbitaceae) seed oil prevents benzo(a)pyrene-induced prostate cancer in vitro and in vivo.

Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C.

Pitfalls of using sequence databases for heterologous expression studies - a technical review.

Synthesis of DNA fragments based on gene sequences that are available in public resources has become an efficient and affordable method that has gradually replaced traditional cloning efforts such as PCR cloning from cDNA. However, database entries based on genome sequencing results are prone to errors which can lead to false sequence information and, ultimately, errors in functional characterisation of proteins such as ion channels and transporters in heterologous expression systems. We have identified five common problems that repeatedly appear in public resources: (1) Not every gene has yet been annotated; (2) not all gene annotations are necessarily correct; (3) transcripts may contain automated corrections; (4) there are mismatches between gene, mRNA and protein sequences; and (5) splicing patterns often lack experimental validation.

Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt-mTOR and Cyclin-CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines.

Combined cisplatin-gemcitabine treatment causes rapid resistance development in patients with advanced urothelial carcinoma. The present study investigated the potential of the natural isothiocyanates (ITCs) allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to suppress growth and proliferation of gemcitabine- and cisplatin-resistant bladder cancer cells lines. Sensitive and gemcitabine- and cisplatin-resistant RT112, T24, and TCCSUP cells were treated with the ITCs, and tumor cell growth, proliferation, and clone formation were evaluated.

Plant-Derived Sulforaphane Suppresses Growth and Proliferation of Drug-Sensitive and Drug-Resistant Bladder Cancer Cell Lines In Vitro.

Combined cisplatin-gemcitabine (GC) application is standard for treating muscle-invasive bladder cancer. However, since rapid resistance to treatment often develops, many patients turn to supplements in the form of plant-based compounds. Sulforaphane (SFN), derived from cruciferous vegetables, is one such compound, and the present study was designed to investigate its influence on growth and proliferation in a panel of drug-sensitive bladder cancer cell lines, as well as their gemcitabine- and cisplatin-resistant counterparts.

Taste Receptor Activation in Tracheal Brush Cells by Denatonium Modulates ENaC Channels via Ca, cAMP and ACh.

Mucociliary clearance is a primary defence mechanism of the airways consisting of two components, ciliary beating and transepithelial ion transport (I). Specialised chemosensory cholinergic epithelial cells, named brush cells (BC), are involved in regulating various physiological and immunological processes. However, it remains unclear if BC influence I.

Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses.

The Unc119 protein mediates transport of myristoylated proteins to the photoreceptor outer segment, a specialized primary cilium. This transport activity is regulated by the GTPase Arl3 as well as by Arl13b and Rp2 that control Arl3 activation/inactivation. Interestingly, Unc119 is also enriched in photoreceptor synapses and can bind to RIBEYE, the main component of synaptic ribbons.

Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells.

Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable.

Of Humans and Gerbils- Independent Diversification of Neuroligin-4 Into X- and Y-Specific Genes in Primates and Rodents.

The neural cell adhesion protein neuroligin-4 has puzzled neuroscientists and geneticist alike for almost two decades. Its clinical association with autism spectrum disorders (ASD) is well established, however, its diversification into sex chromosome-specific copies, and , remains uncharted territory. Just recently, the presence of substantial neuroligin-4 sequence differences between humans and laboratory mice, in which is a pseudoautosomal gene, could be explained as a consequence of dramatic changes affecting the pseudoautosomal region on both sex chromosomes in a subset of rodents, the clade eumuroida.

RIBEYE B-Domain Is Essential for RIBEYE A-Domain Stability and Assembly of Synaptic Ribbons.

Synaptic ribbons are presynaptic specializations that define eponymous ribbon synapses. Synaptic ribbons are largely composed of RIBEYE, a protein containing an N-terminal A-domain and a carboxyterminal B-domain that is identical with CtBP2, a NAD(H)-binding transcriptional co-repressor. Previously we showed that synaptic ribbons are completely absent in RIBEYE knockout mice in which the RIBEYE A-domain-encoding exon had been deleted, but CtBP2 is still made, demonstrating that the A-domain is required for synaptic ribbon assembly.

Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway.

Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro.

Insulin-like Growth Factor-1 Influences Prostate Cancer Cell Growth and Invasion through an Integrin α3, α5, αV, and β1 Dependent Mechanism.

Insulin-like growth factor-1 (IGF-1)-related signaling is associated with prostate cancer progression. Links were explored between IGF-1 and expression of integrin adhesion receptors to evaluate relevance for growth and migration. Androgen-resistant PC3 and DU145 and androgen-sensitive LNCaP and VCaP prostate cancer cells were stimulated with IGF-1 and tumor growth (all cell lines), adhesion and chemotaxis (PC3, DU145) were determined.

Antiangiogenic Properties of Axitinib versus Sorafenib Following Sunitinib Resistance in Human Endothelial Cells-A View towards Second Line Renal Cell Carcinoma Treatment.

Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors predominate as first-line therapy options for renal cell carcinoma. When first-line TKI therapy fails due to resistance development, an optimal second-line therapy has not yet been established. The present investigation is directed towards comparing the anti-angiogenic properties of the TKIs, sorafenib and axitinib on human endothelial cells (HUVECs) with acquired resistance towards the TKI sunitinib.

Deciphering the Molecular Machinery-Influence of sE-Cadherin on Tumorigenic Traits of Prostate Cancer Cells.

The serum level of soluble (s)E-cadherin is elevated in several malignancies, including prostate cancer (PCa). This study was designed to investigate the effects of sE-cadherin on the behavior of PCa cells in vitro, with the aim of identifying a potential therapeutic target. Growth as well as adhesive and motile behavior were evaluated in PC3, DU-145, and LNCaP cells.