A comparative Proteomics Analysis Identified Differentially Expressed Proteins in Pancreatic Cancer–Associated Stellate Cell Small Extracellular Vesicles

Human pancreatic stellate cells (HPSCs) are an essential stromal component and mediators of pancreatic ductal adenocarcinoma (PDAC) progression. Small extracellular vesicles (sEVs) are membrane-enclosed nanoparticles involved in cell-to-cell communications and are released from stromal cells within PDAC. A detailed comparison of sEVs from normal pancreatic stellate cells (HPaStec) and from PDAC-associated stellate cells (HPSCs) remains a gap in our current knowledge regarding stellate cells and PDAC. We hypothesized there would be differences in sEVs secretion and protein expression that might contribute to PDAC biology. To test this hypothesis, we isolated sEVs using ultracentrifugation followed by characterization by electron microscopy and Nanoparticle Tracking Analysis. We report here our initial observations. First, HPSC cells derived from PDAC tumors secrete a higher volume of sEVs when compared to normal pancreatic stellate cells (HPaStec). Although our data revealed that both normal and tumor-derived sEVs demonstrated no significant biological effect on cancer cells, we observed efficient uptake of sEVs by both normal and cancer epithelial cells. Additionally, intact membrane-associated proteins on sEVs were essential for efficient uptake. We then compared sEV proteins isolated from HPSCs and HPaStecs cells using liquid chromatography–tandem mass spectrometry. Most of the 1481 protein groups identified were shared with the exosome database, ExoCarta. Eighty-seven protein groups were differentially expressed (selected by 2-fold difference and adjusted p value ≤0.05) between HPSC and HPaStec sEVs. Of note, HPSC sEVs contained dramatically more CSE1L (chromosome segregation 1–like protein), a described marker of poor prognosis in patients with pancreatic cancer. Based on our results, we have demonstrated unique populations of sEVs originating from stromal cells with PDAC and suggest that these are significant to cancer biology. Further studies should be undertaken to gain a deeper understanding that could drive novel therapy.     

Natural incorporation of mercury in bone

Mercury (Hg) is a highly toxic element that causes bone defects and malformations. Structure and surface analyses using quantitative x-ray diffraction using the Rietveld method, High-Resolution Transmission Electron Microscopy and nanodiffraction analyses, and Fourier-Transformed Infrared spectroscopy showed that bone enriched naturally with Hg (≤ 2.3 %) contained Hg₃PO₄ [(Hg₂)₃(PO₄)₂] and HgO. Bone [mostly as apatite, verified as carboxyapatite Ca₁₀(PO₄)₄(CO₃)₃(OH)₂(s)] and cinnabar (HgS) dissolved releasing Hg⁺ (existing as dimer Hg₂²⁺) and PO₄³⁻, both of which became immobilized as (Hg₂)₃(PO₄)₂. Besides, released Hg²⁺ became oxidized to form HgO. The outcome of this work is novel, provided that only a handful of stable compounds of Hg₂²⁺ are found in nature.     

Multi-lineage Lung Regeneration by Stem Cell Transplantation across Major Genetic Barriers

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A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

Dietary boron does not affect tooth strength,micro-hardness,and density,but affects tooth mineral composition and alveolar bone mineral density in rabbits fed a high-energy diet

The objective of this study was to determine whether dietary boron (B) affects the strength, density and mineral composition of teeth and mineral density of alveolar bone in rabbits with apparent obesity induced by a high-energy diet. Sixty female, 8-month-old, New Zealand rabbits were randomly assigned for 7 months into five groups as follows: (1) control 1, fed alfalfa hay only (5.91 MJ/kg and 57.5 mg B/kg); (2) control 2, high energy diet (11.76 MJ and 3.88 mg B/kg); (3) B10, high energy diet + 10 mg B gavage/kg body weight/96 h; (4) B30, high energy diet + 30 mg B gavage/kg body weight/96 h; (5) B50, high energy diet + 50 mg B gavage/kg body weight/96 h. Maxillary incisor teeth of the rabbits were evaluated for compression strength, mineral composition, and micro-hardness. Enamel, dentin, cementum and pulp tissue were examined histologically. Mineral densities of the incisor teeth and surrounding alveolar bone were determined by using micro-CT. When compared to controls, the different boron treatments did not significantly affect compression strength, and micro-hardness of the teeth, although the B content of teeth increased in a dose-dependent manner. Compared to control 1, B50 teeth had decreased phosphorus (P) concentrations. Histological examination revealed that teeth structure (shape and thickness of the enamel, dentin, cementum and pulp) was similar in the B-treated and control rabbits. Micro CT evaluation revealed greater alveolar bone mineral density in B10 and B30 groups than in controls. Alveolar bone density of the B50 group was not different than the controls. Although the B treatments did not affect teeth structure, strength, mineral density and micro-hardness, increasing B intake altered the mineral composition of teeth, and, in moderate amounts, had beneficial effects on surrounding alveolar bone.     

Genetics and Mechanism of Resistance to Meloidogyne arenaria in Peanut Germplasm

Segregation of resistance to Meloidogyne arenaria in six BC₅F₂ peanut breeding populations was examined in greenhouse tests. Chi-square analysis indicated that segregation of resistance was consistent with resistance being conditioned by a single gene in three breeding populations (TP259-3, TP262-3, and TP271-2), whereas two resistance genes may be present in the breeding populations TP259-2, TP263-2, and TP268-3. Nematode development in clonally propagated lines of resistant individuals of TP262-3 and TP263-2 was compared to that of the susceptible cultivar Florunner. Juvenile nematodes readily penetrated roots of all peanut genotypes, but rate of development was slower (P = 0.05) in the resistant genotypes than in Florunner. Host cell necrosis indicative of a hypersensitive response was not consistently observed in resistant genotypes of either population. Three RFLP loci linked to resistance at distances of 4.2 to 11.0 centiMorgans were identified. Resistant and susceptible alleles for RFLP loci R2430E and R2545E were quite distinct and are useful for identifying individuals homozygous for resistance in segregating populations.