LAPTM4B-mediated hepatocellular carcinoma stem cell proliferation and MDSC migration: implications for HCC progression and sensitivity to PD-L1 monoclonal antibody therapy.

In hepatocellular carcinoma (HCC), immunotherapy is vital for advanced-stage patients. However, diverse individual responses and tumor heterogeneity have resulted in heterogenous treatment outcomes. Our mechanistic investigations identified LAPTM4B as a crucial gene regulated by ETV1 (a transcription factor), especially in liver cancer stem cells (LCSCs).

Clinical value of chemiluminescence method for detection of antinuclear antibody profiles.

Background: Antinuclear antibodies (ANAs) are crucial in diagnosing autoimmune diseases, mainly systemic lupus erythematosus (SLE). This study aimed to compare the performance of chemiluminescence assay (CLIA) and line immunoassay (LIA) in detecting ANAs in patients with autoimmune diseases, evaluate their diagnostic accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. Specimens from patients with autoimmune diseases and physical examination specimens were collected to parallel detect specific antibodies.

Digital Image Analysis of Ki67 Heterogeneity Improves the Diagnosis and Prognosis of Gastroenteropancreatic Neuroendocrine Neoplasms.

Ki67 is a reliable grading and prognostic biomarker of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). The intratumor heterogeneity of Ki67, correlated with tumor progression, is a valuable factor that requires image analysis. The application of digital image analysis (DIA) enables new approaches for the assessment of Ki67 heterogeneity distribution.

Automatic segmentation of prostate magnetic resonance imaging using generative adversarial networks.

Background: Automatic and detailed segmentation of the prostate using magnetic resonance imaging (MRI) plays an essential role in prostate imaging diagnosis. Traditionally, prostate gland was manually delineated by the clinician in a time-consuming process that requires professional experience of the observer. Thus, we proposed an automatic prostate segmentation method, called SegDGAN, which is based on a classic generative adversarial network model.

Dioleoylphosphatidylglycerol Accelerates Corneal Epithelial Wound Healing.

Purpose: In contact with the external environment, the cornea can easily be injured. Although corneal wounds generally heal rapidly, the pain and increased risk of infection associated with a damaged cornea, as well as the impaired healing observed in some individuals, emphasize the need for novel treatments to accelerate corneal healing. We previously demonstrated in epidermal keratinocytes that the glycerol channel aquaporin-3 (AQP3) interacts with phospholipase D2 (PLD2) to produce the signaling phospholipid phosphatidylglycerol (PG), which has been shown to accelerate skin wound healing in vivo.

Soy Phosphatidylglycerol Reduces Inflammation in a Contact Irritant Ear Edema Mouse Model In Vivo.

We have previously shown that phosphatidylglycerol (PG) regulates the function of keratinocytes, the predominant cells that compose the epidermis, inhibiting the proliferation of rapidly dividing keratinocytes. In particular, soy PG, a PG mixture with a high proportion of polyunsaturated fatty acids, is efficacious at inhibiting these proliferating keratinocytes. Psoriasis is a skin disorder characterized by hyperproliferation of keratinocytes and inflammation.

Design of broadband graphene-metamaterial absorbers for permittivity sensing at mid-infrared regions.

In this paper, a tunable broadband metamaterial absorber (MA) based on graphene is investigated theoretically and numerically at mid-infrared regions. Compared with the previously reported multiband graphene-based MAs, a broad bandwidth of 11.7 THz with the absorption over 90% is obtained in the proposed MA, which is composed of a Jerusalem cross (JC) metal encrusting into the slot graphene layer in the top layer.

Microwave properties of the single-layer periodic structure composites composed of ethylene-vinyl acetate and polycrystalline iron fibers.

A single-layer microwave absorbing structure composed of the ethylene-vinyl acetate (EVA) powders and polycrystalline iron fibers (PIFs) with thickness of 2 mm, which has a periodic array of circular hole, is designed and fabricated using the mechanical method. We show that the reflection loss (RL) can be easily adjusted by changing the geometric parameters. The maximum RL is 18.

Healthy lifestyle intervention for adult clinic patients with type 2 diabetes mellitus.

Background: Diet and exercise therapy have been reported to be effective in improving blood glucose control and are an important part of treatment of type 2 diabetes mellitus.

Objective: The goal of this study is to examine the efficacy of a healthy lifestyle intervention for adult clinic patients with type 2 diabetes mellitus, as measured by Hgb-A1c, cardiovascular indicators, physical activity, weight, and BMI. Also of interest are optimal strategies for subject recruitment, the number of intervention sessions attended, and participant use of the Fitbit watch to monitor their physical activity and track food and beverage consumption.

Obesity, hypertension and aldosterone: is leptin the link?

Obesity is a serious health hazard with rapidly increasing prevalence in the United States. In 2014, the World Health Organization estimated that nearly 2 billion people worldwide were overweight with an estimated 600 million of these obese. Obesity is associated with many chronic diseases, including cardiovascular disease and hypertension.

Composite scaffolds of nano-hydroxyapatite and silk fibroin enhance mesenchymal stem cell-based bone regeneration via the interleukin 1 alpha autocrine/paracrine signaling loop.

Composite scaffolds of nano-hydroxyapatite (nHAp) and silk fibroin (SF) have been reported to promote bone regeneration mainly through signaling pathways associated with cell-biomaterial interaction. However, it is unclear whether soluble factors also play a role in osteoinduction with nHAp-SF. In this study, we confirmed the biocompatibility and superior osteoinductivity of nHAp-SF scaffolds versus SF scaffolds both in vitro and on a calvarial defect model in vivo.

Distinct effects of different phosphatidylglycerol species on mouse keratinocyte proliferation.

We have previously shown that liposomes composed of egg-derived phosphatidylglycerol (PG), with a mixed fatty acid composition (comprising mainly palmitate and oleate), inhibit the proliferation and promote the differentiation of rapidly dividing keratinocytes, and stimulate the growth of slowly proliferating epidermal cells. To determine the species of PG most effective at modulating keratinocyte proliferation, primary mouse keratinocytes were treated with different PG species, and proliferation was measured. PG species containing polyunsaturated fatty acids were effective at inhibiting rapidly proliferating keratinocytes, whereas PG species with monounsaturated fatty acids were effective at promoting proliferation in slowly dividing cells.

The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial.

Cell wounding activates phospholipase D in primary mouse keratinocytes.

Plasma membrane disruptions occur in mechanically active tissues such as the epidermis and can lead to cell death if the damage remains unrepaired. Repair occurs through fusion of vesicle patches to the damaged membrane region. The enzyme phospholipase D (PLD) is involved in membrane traffickiing; therefore, the role of PLD in membrane repair was investigated.

The potential use of protein kinase D inhibitors for prevention/treatment of epidermal tumors.

Background: The serine/threonine kinase protein kinase D (PKD) has been proposed to be a pro-proliferative, anti-differentiative signal in epidermal keratinocytes. Indeed, the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA) induces biphasic PKD activation, which mirrors the biphasic response of initial differentiation followed by proliferation and tumor promotion seen in TPA-treated keratinocytes in vitro and epidermis in vivo.

Objective: Our objective was to test the idea that PKD's pro-proliferative and/or anti-differentiative effects in keratinocytes contribute to TPA-induced tumorigenesis.

Impact of glucose-dependent insulinotropic peptide on age-induced bone loss.

Unlabelled: GIP is an important hormonal link between nutrition and bone formation. We show for the first time that BMSCs express functional GIP receptors, that expression decreases with aging, and that elevations in GIP can prevent age-associated bone loss.

Introduction: We previously showed that C57BL/6 mice lose bone mass as they age, particularly between 18 and 24 mo of age.

A potential role for the phospholipase D2-aquaporin-3 signaling module in early keratinocyte differentiation: production of a phosphatidylglycerol signaling lipid.

In keratinocytes aquaporin-3 (AQP3), an efficient glycerol transporter, is associated with phospholipase D2 (PLD2) in caveolin-rich membrane microdomains. PLD catalyzes both phospholipid hydrolysis to produce phosphatidate and a transphosphatidylation reaction using primary alcohols to generate phosphatidylalcohols. As PLD2 can utilize the physiological alcohol glycerol to form phosphatidylglycerol (PG), we hypothesized that AQP3 provides glycerol to PLD2 for PG synthesis, which then modulates keratinocyte function.

Expression of caspase-14 reduces tumorigenicity of skin cancer cells.

Background: The green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) possesses anti-carcinogenic properties and was found to induce terminal differentiation in epidermal keratinocytes. Caspase-14, a member of the caspase family associated with epithelial cell differentiation, planned cell death, and barrier formation, is induced by EGCG in normal human epidermal keratinocytes but not in cancer cells.

Materials And Methods: A human epidermoid cancer cell line, A431, was co-transfected with a caspase-14-expressing pCMV vector and a GFP/neo-etpressingpCMVvector.

Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass.

Glucose-dependent insulinotropic peptide (GIP) is an intestinally secreted hormone the release of which is stimulated by nutrient ingestion. We previously reported that GIP receptors are present in osteoblastic cells and that GIP increases collagen type I synthesis and alkaline phosphatase activity in isolated osteoblasts. We have also shown that osteoclasts express GIP receptors and that GIP inhibits osteoclastic activity and differentiation.

Effects of glucose-dependent insulinotropic peptide on osteoclast function.

Acute nutrient ingestion leads to a rapid inhibition of bone resorption while effects on makers of bone formation are less marked or absent, suggesting that there is a transient shift toward skeletal accretion in the immediate postprandial period. The cellular bases for these effects are not clear. Glucose-dependent insulinotropic peptide (GIP), a known modulator of glucose-induced insulin secretion, is secreted from intestinal endocrine cells in response to nutrient ingestion.

Effects of glucose-dependent insulinotropic peptide on behavior.

Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone that rises rapidly in response to nutrient ingestion. The GIP receptor is widely expressed in the brain including the brain stem, telencephalon, diencephalon, olfactory bulb, pituitary, and cerebellum. Until recently it was not clear what the endogenous ligand for this receptor was because no GIP expression had been demonstrated in the brain.

Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone, which is secreted from endocrine cells in the small intestine after meal ingestion. GIP has been shown to affect osteoblastic function in vitro; however, the in vivo effects of GIP on bone remodeling remain unclear. In the present study, we investigated the role of GIP in modulating bone turnover, by evaluating serum markers of bone turnover, bone density, bone morphology, and changes in biomechanical bone strength over time (one to five months) in GIP receptor knockout mice (GIPR-/- mice).

Carboxy-terminal PTH fragments stimulate [3H]thymidine incorporation in vascular endothelial cells.

We have previously reported that the intact PTH molecule (1-84) stimulates proliferation of human umbilical vein endothelial cells (HUVECs). To define the bioactive portion of the PTH molecule we utilized amino, mid and carboxy-terminal PTH fragments. Carboxy- but not amino-terminal fragments were equivalent to the intact PTH molecule in stimulating [3H]thymidine incorporation in HUVEC.

Multiple melanocortin receptors are expressed in bone cells.

Melanocortin receptors belong to the seven transmembrane domain, G-protein coupled family of receptors. There are five members of this receptor family labeled MC1R-MC5R. These receptors are activated by fragments derived from a larger molecule, proopiomelanocortin (POMC) and include ACTH, alpha beta and gamma-MSH and beta-endorphin.