A high throughput blood-brain barrier model incorporating shear stress with improved predictive power for drug discovery.

The blood-brain barrier is a key structure regulating the health of the brain and access of drugs and pathogens to neural tissue. Shear stress is a key regulator of the blood-brain barrier; however, the commonly used multi-well vitro models of the blood-brain barrier do not incorporate shear stress. In this work, we designed and validated a high-throughput system for simulating the blood-brain barrier that incorporates physiological flow and incorporates an optimized cellular model of the blood-brain barrier. This system can perform assays of blood-brain barrier function with shear stress, with 48 independent assays simultaneously. Using the high throughput assay, we conducted drug screening assays to explore the effects of compounds for opening or closing blood-brain barrier. Our studies revealed that assays with shear stress were more predictive and were able to identify compounds known to modify the blood-brain barrier function while static assays were not. Overall, we demonstrate an optimized, high throughput assay for simulating the blood-brain barrier that incorporates shear stress and is practical for use in drug screening and other high throughput studies of toxicology.

How does calcium and sodium in saline water affect the potential of different rates and size of sugarcane biochar to soil water repellency remediation?

Soil water repellency (SWR) is a growing problem in arid and semiarid regions with non-saline water limitations. The objective of this study was to investigate the potential of different rates and sizes of sugarcane biochar on reducing soil water hydrophobicity when using saline and non-saline water. Eleven sugarcane biochar application rates from 0 to 10% with two different sizes including <0.25 and 0.25-1 mm were studied. The experiment was conducted in two strongly and extremely water-repellent soil. In addition, to investigate the effect of electrolyte concentration on biochar potential for SWR reduction, calcium chloride and sodium chloride electrolyte solutions with 5 concentrations including 0, 0.15, 0.3, 0.45 and 0.6 mol L-1 were considered. The results showed that both sizes of biochar reduced the soil water repellency. While in strongly repellent soil the 4% biochar was enough to change the soil from strongly repellent to hydrophilic, in extremely water-repellent soil, the use of 8% of fine biochar and 6% of coarse biochar changed the extremely water-repellent soil to slightly hydrophobic and strongly hydrophobic respectively. Increasing the electrolyte concentration caused the expansion of soil hydrophobicity and reduced the positive effect of biochar to water repellency management. Increasing the electrolyte concentration in sodium chloride solution has a greater effect on increasing hydrophobicity than in calcium chloride solution. In conclusion, biochar could suggest as a soil-wetting agent in these two hydrophobic soils. However, the salinity of water and the its dominant ion could increase the amount of biochar for soil repellency reduction.

Bioengineering Approaches to Improve Gynecological Cancer Outcomes.

Gynecological cancers are diagnosed in over a million females worldwide, with ovarian, endometrial (uterine), and cervical the most common. Here, we highlight recent progress by bioengineers to improve screening and diagnosis for these diseases, including potential point-of-care approaches. We provide particular attention to the use of tissue engineering, biomaterials, microfluidics, and organoids to identify mechanisms regulating disease progression and predict therapeutic responses. We also highlight opportunities for engineers to address the racial/ethnic/geographic disparities that continue to impact gynecological cancer outcomes. A challenge to improve outcomes for all gynecological cancers will be to expand the diversity of patients included in basic/clinical research to better capture the confounding effects of social/economic variables on disease progression.

Optimized design of a hyperflexible sieve electrode to enhance neurovascular regeneration for a peripheral neural interface.

One in 190 Americans is currently living with the loss of a limb resulted from injury, amputation, or neurodegenerative disease. Advanced neuroprosthetic devices combine peripheral neural interfaces with sophisticated prosthetics and hold great potential for the rehabilitation of impaired motor and sensory functions. While robotic prosthetics have advanced very rapidly, peripheral neural interfaces have long been limited by the capability of interfacing with the peripheral nervous system. In this work, we developed a hyperflexible regenerative sieve electrode to serve as a peripheral neural interface. We examined tissue neurovascular integration through this novel device. We demonstrated that we could enhance the neurovascular invasion through the device with directional growth factor delivery. Furthermore, we demonstrated that we could reduce the tissue reaction to the device often seen in peripheral neural interfaces. Finally, we show that we can create a stable tissue device interface in a long-term implantation that does not impede the normal regenerative processes of the nerve. Our study developed an optimal platform for the continued development of hyperflexible sieve electrode peripheral neural interfaces.

Biomechanical regulation of breast cancer metastasis and progression.

Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.

On the Three-Dimensional Correlation Between Myofibroblast Shape and Contraction.

Myofibroblasts are responsible for wound healing and tissue repair across all organ systems. In periods of growth and disease, myofibroblasts can undergo a phenotypic transition characterized by an increase in extracellular matrix (ECM) deposition rate, changes in various protein expression (e.g., alpha-smooth muscle actin (αSMA)), and elevated contractility. Cell shape is known to correlate closely with stress-fiber geometry and function and is thus a critical feature of cell biophysical state. However, the relationship between myofibroblast shape and contraction is complex, even as well in regards to steady-state contractile level (basal tonus). At present, the relationship between myofibroblast shape and basal tonus in three-dimensional (3D) environments is poorly understood. Herein, we utilize the aortic valve interstitial cell (AVIC) as a representative myofibroblast to investigate the relationship between basal tonus and overall cell shape. AVICs were embedded within 3D poly(ethylene glycol) (PEG) hydrogels containing degradable peptide crosslinkers, adhesive peptide sequences, and submicron fluorescent microspheres to track the local displacement field. We then developed a methodology to evaluate the correlation between overall AVIC shape and basal tonus induced contraction. We computed a volume averaged stretch tensor ⟨U⟩ for the volume occupied by the AVIC, which had three distinct eigenvalues (λ1,2,3=1.08,0.99, and 0.89), suggesting that AVIC shape is a result of anisotropic contraction. Furthermore, the direction of maximum contraction correlated closely with the longest axis of a bounding ellipsoid enclosing the AVIC. As gel-imbedded AVICs are known to be in a stable state by 3 days of incubation used herein, this finding suggests that the overall quiescent AVIC shape is driven by the underlying stress-fiber directional structure and potentially contraction level.

Remediation of an oil-contaminated soil by two native plants treated with biochar and mycorrhizae.

Soil contamination by petroleum compounds threatens the health of soil and water resources. This research was conducted with the objective of reaching an efficient technique for the removal or reduction of harmful effects caused by total petroleum hydrocarbons (TPH) in soils. In a greenhouse experiment, the effect of biochar (B), mycorrhizae (M) and combination of mycorrhizae and biochar (M + B) on the growth of two native species; clover (Trifolium arvense) and mallow (Malva sylvestris L.), and removal efficiency of TPH (16.79 mg kg-1) from an oil-contaminated soil were studied. The plant analyses after 50 days of growth period showed a significant (p ≤ 0.05) increase in shoot dry weight of mallow in B and M + B treatments but no significant effect was observed for clover compared to the control (C). The initial TPH concentration, determined by gas chromatography technique was reduced from 9.4% in unplanted soil until 56.4% (clover) and 55.9% (mallow) in M + B treatment. The relative concentration of long chain alkanes (LCAs) were also reduced when treatments were applied, in which the highest and lowest reductions was found in C21-C25 and C11-C15, respectively, though octacosane (C28) was increased or unchanged in soil. This result suggests that likely the occurrence of C28 in the mycorrhizal hyphae or the higher removal of the other alkanes increase octacosane relative concentration in soil, which more research is necessary.

Phytoremediation of a petroleum-polluted soil by native plant species in Lorestan Province, Iran.

Petroleum hydrocarbons are potentially toxic for organisms due to the inherent properties, such as solubility, volatility, and biodegradability. The petroleum materials released from corroded old pipelines would pollute soils, shallow groundwater and air as a consequence, and threat the health of human and environment. Therefore, the removal of these compounds from environment is vital. The stability of these pollutants at the soil and their gradual accumulation over time would disrupt the normal function of the soil, such as reduced agricultural capability. In this research, the influence of two plant species (Bromus tectorum L. and Festuca arundinacea) with different amendments including arbuscular mycorrhizal fungi, alfalfa residues, and nutrient solution on the degradation rate of petroleum hydrocarbons in soil was studied. The results showed that the most effective treatment for petroleum remediation was related to B. tectorum L. plant when treated with mycorrhizal fungi and nutrient solution. The degradation rate during 40 days was about 83.27% when compared to the control. Arbuscular mycorrhizal associations are important in the restoration of degraded ecosystems because of the benefits to their symbiotic partners. This fungal phytotechnological mechanism is still in its infancy and there has been little research on aged-contaminated soils.

Environmental impact assessment of industrial activities on heavy metals distribution in street dust and soil.

Street dust and soil are important materials for evaluating the contaminants level in industrial areas. Detailed size-resolved distribution of metal(loid)s in street dusts and soils influenced by industrial activities has rarely been investigated. This study was carried out to understand how industrialization might affect the size distribution of metal(loid)s concentration and contamination level in the street dust and soil from Murcia, southern Spain. An industrial and a natural areas were selected and surface soil and street dust samples were taken. They were fractionated into eleven size classes and total concentrations of Pb, Zn, Cu, Cd, Cr, Ni, As and Fe were determined in both the bulk samples and their fractions. Enrichment factor, geoaccumulation index, and mass loading of different heavy metal(loids) were calculated. The results indicated that the street dust from natural and industrial areas had almost the same particle size distribution, both containing higher percentage of coarse-sized particles than the soil. Industrialization seems to have only slightly affected the concentration of most elements studied in the soil. In contrast, the concentrations of the heavy elements in bulk industrial dust samples and all their size fractions were extremely higher than those from the natural area. This means that the industrial activities only affected the size dependency of the concentration (contamination level) of certain elements (Pb, Zn, Cu, Cd, and Cr) in the street dust, but not in the soil.

Provenance and environmental risk of windblown materials from mine tailing ponds, Murcia, Spain.

Atmospheric particulates play a vital role in the transport of potentially toxic metals, being an important exposure pathways of people to toxic elements, which is faster and can occur in a much larger scale than water, soil and biota transport. Windblown materials in abandoned tailing ponds have not been well examined. The objectives of this investigation were: to study the major physical and geochemical properties of the materials eroded by wind inside the tailing ponds, and to understand the relative contribution of different sources to its heavy metals concentration. Study area is located in Cartagena-La Union mining district (SE Spain), where metallic mining of Fe, Pb and Zn has been developed for more than 2500 years. Wind-eroded particulates were monthly collected at 3 different heights (20, 50, and 80 cm) from the ground for a period of a full year using 4 dust collectors. Four tailing samples and 4 surface soil samples from the surrounding hills were also taken. Dust, soil, and tailing samples were examined for pH, particle size distribution, electrical conductivity, calcium carbonate content, Pb, Cu, Zn, Cd, Mn, Co, Ni, Ti and Zr concentrations. The results indicated that very coarse textured, slightly saline, and almost neutral wind-eroded deposits were generated with a very high temporal variability throughout the year. They also showed that the concentration of Cd, Mn, Pb and Zn, in the dust samples is extraordinarily high (18, 1254, 1831, and 5747 mg kg-1 respectively), whereas Co, Ni, and Cu had concentrations into the range of background concentrations found in the Earth's crust (3.8, 12, and 60 mg kg-1 respectively). Besides, the concentration of both categories of heavy metals in the dust samples was higher than that in tailing and less than that of the soils. The barren surfaces of tailing ponds and also the surface soils of the surrounding area seem to be the major contributors to the dust collected. Therefore, abandoned mines as well as their tailing ponds should be rehabilitated by proper technologies and then well stabilized and/or covered by appropriate plant vegetation to control the transfer, particularly by air, of environmentally hazardous materials to other areas.

Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy.

OBJECTIVE: In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. METHODS: Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and 17ß-estradiol, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. RESULTS: We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and 17ß-estradiol levels, and a reduced frequency of macrophages and uNK cells. CONCLUSION: Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes.

Evaluation of chloropyromorphite stability in the rhizosphere of and in a sand culture.

Chloropyromorphite (Pb(PO)Cl), CP, is the most stable lead (Pb) mineral under normal environmental conditions and precipitates in Pb-contaminated soils by addition of phosphorous (P). A sand culture experiment was conducted to evaluate the efficiency of and roots to dissolve CP in the presence and in the absence of P source. The results showed that the rhizosphere of the plants had lower soluble P and Pb compared with the bulk, which can be attributed to a higher pH in the rhizosphere. Mineralogical transformations of CP in the root surface of the plants including lanarkite (PbSO.PbO) has been confirmed by X-ray diffraction and scanning electron microscopy techniques. Decrease in soluble P in the rhizosphere as a consequence of P uptake by the plant roots may be a reason for CP dissolution. This study indicates that the dissolution of CP can be promoted by rhizosphere processes.

The immunomodulatory effects of abortion-prone mice decidual and serum soluble factors on macrophages and splenocytes.

OBJECTIVES: To determine the immune status of the abortion mouse model at the feto-maternal interface and at the systemic level simultaneously. STUDY DESIGN: Mid-pregnancy serum and decidual cell supernatants (DS) were obtained from abortion and non-abortion mouse models. The effect of serum and DS on PHA or LPS-induced lymphocyte proliferation was investigated by MTT reduction assay. Treated macrophages and LPS-stimulated macrophages were evaluated for viability and also for nitric oxide (NO) production by Griess reagent. RESULTS: Our results showed that DS from the abortion mouse model significantly decreased LPS-stimulated splenocyte proliferation, and increased proliferation in PHA-stimulated splenocytes, compared with that in the non-abortion mouse model. Proliferation assays for mid-pregnancy serum were the same on LPS- and PHA-stimulated splenocytes. NO production was decreased by non-abortion DS, similar to that observed for serum treatment in LPS-stimulated macrophages in abortion mice. CONCLUSIONS: These findings suggest that in the abortion mouse model, soluble factors within the decidua are more effective than serum soluble factors in altering immune responses that may be involved in the complex process of fetal rejection.

Estimation of gamma- and X-ray photons buildup factor in soft tissue with Monte Carlo method.

Buildup factor of gamma- and X-ray photons in the energy range 0.2-2MeV in water and soft tissue is computed using Monte Carlo method. The results are compared with the existing buildup factor data of pure water. The difference between soft tissue and water buildup factor is studied. Soft tissue is assumed to have a composition as H(63)C(6)O(28)N. The importance of such work arises from the fact that in medical applications of X- and gamma-ray, soft tissue is usually approximated by water. It is shown that the difference between water and soft tissue buildup factor is usually more than 10%. On the other hand, buildup factor in water resulted from Monte Carlo method is compared with the experimental data appearing in references. It seems there is around 10% error in the reference data as well.