Decreased lung carcinoma cell density on select polymer nanometer surface features for lung replacement therapies

Poly(lactic-co-glycolic) acid (PLGA) has been widely used as a biomaterial in regenerative medicine because of its biocompatibility and biodegradability properties. Previous studies have shown that cells (such as bladder smooth muscle cells, chondrocytes, and osteoblasts) respond differently to nanostructured PLGA surfaces compared with nanosmooth surfaces. The purpose of the present in vitro research was to prepare PLGA films with various nanometer surface features and determine whether lung cancer epithelial cells respond differently to such topographies. To create nanosurface features on PLGA, different sized (190 nm, 300 nm, 400 nm, and 530 nm diameter) polystyrene beads were used to cast polydimethylsiloxane (PDMS) molds which were used as templates to create nanofeatured PLGA films. Atomic force microscopy (AFM) images and root mean square roughness (RMS) values indicated that the intended spherical surface nanotopographies on PLGA with RMS values of 2.23, 5.03, 5.42, and 36.90 nm were formed by employing 190, 300, 400, and 530 nm beads. A solution evaporation method was also utilized to modify PLGA surface features by using 8 wt% (to obtain an AFM RMS value of 0.62 nm) and 4 wt% (to obtain an AFM RMS value of 2.23 nm) PLGA in chloroform solutions. Most importantly, lung cancer epithelial cells adhered less on the PLGA surfaces with RMS values of 0.62, 2.23, and 5.42 nm after four hours of culture compared with any other PLGA surface created here. After three days, PLGA surfaces with an RMS value of 0.62 nm had much lower cell density than any other sample. In this manner, PLGA with specific nanometer surface features may inhibit lung cancer cell density which may provide an important biomaterial for the treatment of lung cancer (from drug delivery to regenerative medicine)

Genome Editing and Induced Pluripotent Stem Cell Technologies for Personalized Study of Cardiovascular Diseases

PURPOSE OF REVIEW: The goal of this review is to highlight the potential of induced pluripotent stem cell (iPSC)-based modeling as a tool for studying human cardiovascular diseases. We present some of the current cardiovascular disease models utilizing genome editing and patient-derived iPSCs. RECENT FINDINGS: The incorporation of genome-editing and iPSC technologies provides an innovative research platform, providing novel insight into human cardiovascular disease at molecular, cellular, and functional level. In addition, genome editing in diseased iPSC lines holds potential for personalized regenerative therapies. The study of human cardiovascular disease has been revolutionized by cellular reprogramming and genome editing discoveries. These exceptional technologies provide an opportunity to generate human cell cardiovascular disease models and enable therapeutic strategy development in a dish. We anticipate these technologies to improve our understanding of cardiovascular disease pathophysiology leading to optimal treatment for heart diseases in the future

Pure nongestational choriocarcinoma of the ovary: a case report

Abstract Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational choriocarcinoma of the ovary is extremely rare, and its diagnosis is very difficult during the reproductive years. We present a case of a 33-year-old woman diagnosed with pure nongestational ovarian choriocarcinoma. Following surgery, multiple courses of a chemotherapy regimen of etoposide, methotrexate, and actinomycin-D (EMA) were effective.</p

Chemical homogeneity of wide binary system: An approach from Near-Infrared spectroscopy

Wide binaries, with separations between two stars from a few AU to more than several thousand AU, are valuable objects for various research topics in Galactic astronomy. As the number of newly reported wide binaries continues to increase, studying the chemical abundances of their component stars becomes more important. We conducted high-resolution near-infrared (NIR) spectroscopy for six pairs of wide binary candidates using the Immersion Grating Infrared Spectrometer (IGRINS) at the Gemini-South telescope. One pair was excluded from the wide binary samples due to a significant difference in radial velocity between its component stars, while the remaining five pairs exhibited homogeneous properties in 3D motion and chemical composition among the pair stars. The differences in [Fe/H] ranged from 0.00 to 0.07 dex for these wide binary pairs. The abundance differences between components are comparable to the previous results from optical spectroscopy for other samples. In addition, when combining our data with literature data, it appears that the variation of abundance differences increases in wide binaries with larger separations. However, the SVO2324 and SVO3206 showed minimal differences in most elements despite their large separation, supporting the concept of multiple formation mechanisms depending on each wide binary. This study is the first approach to the chemical properties of wide binaries based on NIR spectroscopy. Our results further highlight that NIR spectroscopy is an effective tool for stellar chemical studies based on equivalent measurements of chemical abundances from the two stars in each wide binary system.Comment: 16 pages, 9 figures, accepted for publication in A

Tempcore Process Simulator to Analyze Microstructural Evolution of Quenched and Tempered Rebar

Featured Application Proposed process simulator can be widely applied to parameter design of industrial Tempcore process with reduced cost and time. Abstract Tempcore process simulator (TPS) has been developed in this study to analyze the microstructural evolution of quenched and tempered rebar. There has been an increasing need to relate the complex microstructures to the resulting properties of quenched and tempered rebar. However, information on such relationships typically requires precise thermal histories imposed on the workpiece. Therefore, TPS, capable of simulating the Tempcore process, has been developed to produce high-fidelity data. TPS mainly consists of a vacuum induction furnace, pilot rolling mill, box furnace, and cooling unit to simulate shop floor operations. A series of experimental tests were successfully carried out with various parameters, such as reheating temperature, water flow, water pressure, and cooling time. The effects of chemical compositions and cooling time on the microstructural evolution and mechanical properties of quenched and tempered rebar have been analyzed to validate the performance of TPS. The results show that TPS can simulate the Tempcore process with a high degree of fidelity and reliability.11Ysciescopu

Directing lineage specification of human mesenchymal stem cells by decoupling electrical stimulation and physical patterning on unmodified graphene

The organization and composition of the extracellular matrix (ECM) have been shown to impact the propagation of electrical signals in multiple tissue types. To date, many studies with electroactive biomaterial substrates have relied upon passive electrical stimulation of the ionic media to affect cell behavior. However, development of cell culture systems in which stimulation can be directly applied to the material – thereby isolating the signal to the cell-material interface and cell–cell contracts – would provide a more physiologically-relevant paradigm for investigating how electrical cues modulate lineage-specific stem cell differentiation. In the present study, we have employed unmodified, directly-stimulated, (un)patterned graphene as a cell culture substrate to investigate how extrinsic electrical cycling influences the differentiation of naïve human mesenchymal stem cells (hMSCs) without the bias of exogenous biochemicals. We first demonstrated that cyclic stimulation does not deteriorate the cell culture media or result in cytotoxic pH, which are critical experiments for correct interpretation of changes in cell behavior. We then measured how the expression of osteogenic and neurogenic lineage-specific markers were altered simply by exposure to electrical stimulation and/or physical patterns. Expression of the early osteogenic transcription factor RUNX2 was increased by electrical stimulation on all graphene substrates, but the mature marker osteopontin was only modulated when stimulation was combined with physical patterns. In contrast, the expression of the neurogenic markers MAP2 and β3-tubulin were enhanced in all electrical stimulation conditions, and were less responsive to the presence of patterns. These data indicate that specific combinations of non- biological inputs – material type, electrical stimulation, physical patterns – can regulate hMSC lineage specification. This study represents a substantial step in understanding how the interplay of electrophysical stimuli regulate stem cell behavior and helps to clarify the potential for graphene substrates in tissue engineering applications

Scutellaria baicalensis

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of Scutellaria baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of S. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of S. baicalensis compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the S. baicalensis extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function

Frontal lobe epilepsy: Clinical characteristics, surgical outcomes and diagnostic modalities

SummaryObjectiveTo identify surgical prognostic factors and to characterize clinical features according to the location of the intracranial ictal onset zone of frontal lobe epilepsy (FLE) in order to assess the role of various diagnostic modalities, including concordances with presurgical evaluations.MethodsWe studied 71 FLE patients who underwent epilepsy surgery and whose outcomes were followed for more than 2 years. Diagnoses were established by standard presurgical evaluation.ResultsClinical manifestations could be categorized into six types: initial focal motor (9 patients), initial versive seizure (15), frontal lobe complex partial seizure (14), complex partial seizure mimicking temporal lobe epilepsy (18), initial tonic elevation of arms (11), and sudden secondary generalized tonic–clonic seizure (4). Thirty-seven patients became seizure-free after surgery. Five patients were deleted in the analysis because of incomplete resection of ictal onset zones. The positive predictive value of interictal EEG, ictal EEG, MRI, PET, and ictal SPECT, respectively were 62.5%, 56.4%, 73.9%, 63.2%, and 63.6%, and the negative predictive value were 46.0%, 44.4%, 53.5%, 44.7%, and 51.7%. No significant relationship was found between the diagnostic accuracy of these modalities and surgical outcome, with the exception of MRI (p=0.029). Significant concordance of two or more modalities was observed in patients who became seizure-free (p=0.011). We could not find any clinical characteristic related to surgical outcome besides seizure frequency. No definite relationship was found between the location of intracranial ictal onset zone and clinical semiology.ConclusionAlthough various diagnostic methods can be useful in the diagnosis of FLE, only MRI can predict surgical outcome. Concordance between presurgical evaluations indicates a better surgical outcome

Multilocus sequence typing (MLST) analysis of Vibrio cholerae O1 El Tor isolates from Mozambique that harbour the classical CTX prophage.

Vibrio cholerae O1 isolates belonging to the Ogawa serotype, El Tor biotype, harbouring the classical CTX prophage were first isolated in Mozambique in 2004. Multilocus sequence typing (MLST) analysis using nine genetic loci showed that the Mozambique isolates have the same sequence type (ST) as O1 El Tor N16961, a representative of the current seventh cholera pandemic. Analysis of the CTX prophage in the Mozambique isolates indicated that there is one type of rstR in these isolates: the classical CTX prophage. It was also found that the ctxB-rstR-rstA-rstB-phs-cep fragment was PCR-amplified from these isolates, which indicates the presence of a tandem repeat of the classical CTX prophage in the genome of the Mozambique isolates. The possible origin of these isolates and the presence of the tandem repeat of the classical prophage in them implicate the presence of the classical CTX phage

Altered renal sodium transporter expression in an animal model of type 2 diabetes mellitus

Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance