Pan-cancer analysis reveals plays an important role in tumorigenesis in multiple tumor types.

The deletion of geranylgeranyl diphosphate synthase 1 () has been reported to inhibit the proliferation of multiple cells. Although emerging evidence has demonstrated a correlation between and cancer, no pan-cancer analysis has been conducted to date. This study explored the potential tumorigenesis of using data from the cancer genome atlas human clinical database.

Involucrasin B suppresses airway inflammation in obese asthma by inhibiting the TLR4-NF-κB-NLRP3 pathway.

Background: Obese asthma is an asthma phenotype that causes more severe lung inflammation and airway hyperresponsiveness than allergic asthma and it is resistant to conventional therapy. Involucrasin B (IB) is a dihydroflavonoid isolated from Shuteria involucrata (Wall.) Wight & Arn.

(±)-Involucrasin D, a pair of enantiomeric bisflavonoid from the roots of and its anti-inflammatory activity.

An undescribed bisflavonoid, named involucrasin D (), along with two known flavonoids, 2(S)7,3',5'-trihydroxydihydroflavone () and sigmone () were isolated from the roots of . A further chiral separation of to yielded a pair of enantiomers (+)- and (-)-. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations.

MYPT1 reduction is a pathogenic factor of erectile dysfunction.

Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed impaired erections as evidenced by reduced intracavernous pressure (ICP).

A Shigella species variant is causally linked to intractable functional constipation.

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA).

The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion.

The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging.

LIMK2 is required for membrane cytoskeleton reorganization of contracting airway smooth muscle.

Airway smooth muscle (ASM) has developed a mechanical adaption mechanism by which it transduces force and responds to environmental forces, which is essential for periodic breathing. Cytoskeletal reorganization has been implicated in this process, but the regulatory mechanism remains to be determined. We here observe that ASM abundantly expresses cytoskeleton regulators Limk1 and Limk2, and their expression levels are further upregulated in chronic obstructive pulmonary disease (COPD) animals.

Distinct Roles of Smooth Muscle and Non-muscle Myosin Light Chain-Mediated Smooth Muscle Contraction.

Both smooth muscle (SM) and non-muscle (NM) myosin II are expressed in hollow organs such as the bladder and uterus, but their respective roles in contraction and corresponding physiological functions remain to be determined. In this report, we assessed their roles by analyzing mice deficient of , a gene encoding the SM myosin regulatory light chain (SM RLC). We find that global -deficient bladders contracted with an apparent sustained phase, despite no initial phase.

GGPP depletion initiates metaflammation through disequilibrating CYB5R3-dependent eicosanoid metabolism.

Metaflammation is a primary inflammatory complication of metabolic disorders characterized by altered production of many inflammatory cytokines, adipokines, and lipid mediators. Whereas multiple inflammation networks have been identified, the mechanisms by which metaflammation is initiated have long been controversial. As the mevalonate pathway (MVA) produces abundant bioactive isoprenoids and abnormal MVA has a phenotypic association with inflammation/immunity, we speculate that isoprenoids from the MVA may provide a causal link between metaflammation and metabolic disorders.

The intragenic microRNA in the dynamin 2 gene contributes to the pathology of X-linked centronuclear myopathy.

Mutations in the myotubularin 1 () gene can cause the fatal disease X-linked centronuclear myopathy (XLCNM), but the underlying mechanism is incompletely understood. In this report, using an disease model, we found that expression of the intragenic microRNA miR-199a-1 is up-regulated along with that of its host gene, dynamin 2 (), in XLCNM skeletal muscle. To assess the role of miR-199a-1 in XLCNM, we crossed with mice and found that the resultant double-knockout mice display markers of improved health, as evidenced by lifespans prolonged by 30% and improved muscle strength and histology.

Golgi-resident TRIO regulates membrane trafficking during neurite outgrowth.

Neurite outgrowth requires coordinated cytoskeletal rearrangements in the growth cone and directional membrane delivery from the neuronal soma. As an essential Rho guanine nucleotide exchange factor (GEF), TRIO is necessary for cytoskeletal dynamics during neurite outgrowth, but its participation in the membrane delivery is unclear. Using co-localization studies, live-cell imaging, and fluorescence recovery after photobleaching analysis, along with neurite outgrowth assay and various biochemical approaches, we here report that in mouse cerebellar granule neurons, TRIO protein pools at the Golgi and regulates membrane trafficking by controlling the directional maintenance of both RAB8 (member RAS oncogene family 8)- and RAB10-positive membrane vesicles.

CPI-17-mediated contraction of vascular smooth muscle is essential for the development of hypertension in obese mice.

Several factors have been implicated in obesity-related hypertension, but the genesis of the hypertension is largely unknown. In this study, we found a significantly upregulated expression of CPI-17 (C-kinase-potentiated protein phosphatase 1 inhibitor of 17 kDa) and protein kinase C (PKC) isoforms in the vascular smooth muscles of high-fat diet (HFD)-fed obese mice. The obese wild-type mice showed a significant elevation of blood pressure and enhanced calcium-sensitized contraction of vascular smooth muscles.

Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons.

As a critical guanine nucleotide exchange factor (GEF) regulating neurite outgrowth, Trio coordinates multiple processes of cytoskeletal dynamics through activating Rac1, Cdc42 and RhoA small GTPases by two GEF domains, but the in vivo roles of these GEF domains and corresponding downstream effectors have not been determined yet. We established multiple lines of knockout mice and assessed the respective roles of Trio GEF domains and Rac1 in axon outgrowth. Knockout of total Trio in cerebellar granule neurons (CGNs) led to an impaired F-actin rearrangement of growth cone and hence a retarded neurite outgrowth.

Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo.

We created a novel paclitaxel (PTX) nanoparticle drug delivery system and compared this to acommercial injection preparation to evaluate the antitumor effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm with potential of -29.

Inflammatory mediators mediate airway smooth muscle contraction through a G protein-coupled receptor-transmembrane protein 16A-voltage-dependent Ca channel axis and contribute to bronchial hyperresponsiveness in asthma.

Background: Allergic inflammation has long been implicated in asthmatic hyperresponsiveness of airway smooth muscle (ASM), but its underlying mechanism remains incompletely understood. Serving as G protein-coupled receptor agonists, several inflammatory mediators can induce membrane depolarization, contract ASM, and augment cholinergic contractile response. We hypothesized that the signal cascade integrating on membrane depolarization by the mediators might involve asthmatic hyperresponsiveness.

Preparation, physical characterization and pharmacokinetic study of paclitaxel nanocrystals.

Paclitaxel (PTX) is a natural broad-spectrum anticancer drug with poor aqueous solubility. PTX nanocrystals were formulated to improve the water solubility, and PTX nanosuspensions were prepared using anti-solvent precipitation, and then organic solvent and surfactants were removed by filtering through a vacuum system. The physical characterization of PTX nanocrystals were measured by transmission electron microscope, X-ray diffraction and differential scanning calorimetry.