Objectives: This study compared the nutritional intakes of early and late preterm infants in a neonatal intensive care unit (NICU) and at home. The dietary problems and the need for community care services for premature infants were further investigated. Methods: This is a cross-sectional and descriptive study on 125 preterm infants and their parents (Early preterm n = 70, Late preterm n = 55). The data were collected by surveying the parents of preterm infants and from hospital medical records. Results: No significant differences were obtained between the early and late preterm infant groups when considering the proportion of feeding types in the NICU and at home. Early preterm infants were fed with a greater amount of additional calories at home and had more hours of tube feeding (P = 0.022). Most preterm infants had feeding problems. However, there was no significant difference between early and late preterm infants in the mental pain of parents, sleeping, feeding, and weaning problems at home. Many parents of preterm babies had no external support, and more than half the parents required community care to take care of their preterm babies. Conclusions Regardless of the gestational age, most preterm infants have several problems with dietary intake. Our study indicates the need to establish community care services for preterm infants.

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.
Administration, Intravesical ; Bacillus ; Cell Wall Skeleton ; Drug Delivery Systems ; Immunotherapy ; Methods ; Mycobacterium bovis ; Nanoparticles ; Product Packaging ; Skeleton ; Solvents ; Urinary Bladder Neoplasms ; Urinary Bladder

Three-dimensional (3D) printing is an additive manufacturing process by which precursor materials are deposited layer by layer to form complex 3D geometries from computer-aided designs, and bioprinting offers the ability to create 3D architecture living cells. Bioprinting methods have been developed rapidly pattern living cells, biological macromolecules, and biomaterials, and an advantage of the 3D microenviroment over traditional 2-dimensional cell culture is the ability to obtain more accurate and reliable data from model about tumor formation, progression, and response to anticancer therapies. This review focuses on recent advances in the use of biopriniting technologies for cancer research, bioprinting physiologically relevant testing platforms for anticancer drug development, and computational modeling for improvement bioprinting technique.
Biocompatible Materials ; Bioprinting ; Cell Culture Techniques ; Computer-Aided Design

Tissue engineering is limited by our inability to adequately vascularize tissues post implantation because all tissue-engineered substitutes (with the exception of cornea and cartilage) require a vascular network to provide the nutrient and oxygen supply needed for their survival. This review gives a brief overview of the processes and factors involved in the vascularization and angiogenesis and summarizes the different strategies to overcome the issue of slow vascularization and angiogenesis in a range of tissue-engineered substitutes. Moreover, we will announce some potential future plans.
Cornea ; Methods* ; Oxygen ; Tissue Engineering

PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.
Administration, Intravesical* ; Animals ; Dextrans ; Drug Liberation ; Fluorescein ; Hydrogel* ; Hydrogels* ; In Vitro Techniques ; Kinetics ; Methods ; Mice* ; Mice, Nude ; Microscopy, Fluorescence ; Optical Imaging ; Phase Transition ; Poloxamer* ; Polymers ; Urinary Bladder* ; Urination

Cancer is the tissue complex consisted with heterogeneous cellular compositions, and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell–cell interactions as well as cell-extracellular matrix play major roles. Conventional cancer models both 2-dimensional and 3-dimensional (3D) present numerous limitations, which restrict their use as biomimetic models for drug screening and fundamental cancer biology studies. Recently, bioprinting biofabrication platform enables the creation of high-resolution 3D structures. Moreover this platform has been extensively used to model multiple organs and diseases, and this versatile technique has further found its creation of accurate models that figure out the complexity of the cancer microenvironment. In this review we will focus on cancer biology and limitations with current cancer models and we discuss vascular structures bioprinting that are critical to the construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinting cancer models and propose future perspectives.
Biology ; Biomimetics ; Bioprinting* ; Cues ; Drug Evaluation, Preclinical ; Neoplasm Metastasis ; Organoids ; Tumor Microenvironment*

Microarray analysis was used to investigate the lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes to overcome cross-talk at non-muscle invasive high-grade (HG)-urothelial carcinoma (UC) of the bladder, gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K, and eIF4E) small interfering RNAs (siRNAs) or rapamycin in 5637 and T24 cell lines. We selected mTOR pathway downstream genes that were suppressed by siRNAs more than 2-fold, or were up-regulated or down-regulated by rapamycin more than 2-fold. We validated mTOR downstream genes with immunohistochemistry using a tissue microarray (TMA) of 125 non-muscle invasive HG-UC patients and knockout study to evaluate the synergistic effect with rapamycin. The microarray analysis selected mTOR pathway downstream genes consisting of 4 rapamycin up-regulated genes (FABP4, H19, ANXA10, and UPK3A) and 4 rapamycin down-regulated genes (FOXD3, ATP7A, plexin D1, and ADAMTS5). In the TMA, FABP4, and ATP7A were more expressed at T1 and FOXD3 was at Ta. ANXA10 and ADAMTS5 were more expressed in tumors ≤ 3 cm in diameter. In a multivariate Cox regression model, ANXA10 was a significant predictor of recurrence and ATP7A was a significant predictor of progression in non-muscle invasive HG-UC of the bladder. In an ATP7A knock-out model, rapamycin treatment synergistically inhibited cell viability, wound healing, and invasion ability compared to rapamycin only. Activity of the ANXA10 and ATP7A mTOR pathway downstream genes might predict recurrence and progression in non-muscle invasive HG-UC of the bladder. ATP7A knockout overcomes rapamycin cross-talk.
Cell Line ; Cell Survival ; Gene Expression ; Gene Ontology ; Humans ; Immunohistochemistry ; Microarray Analysis ; Recurrence* ; RNA, Small Interfering ; Sirolimus ; Urinary Bladder Neoplasms ; Urinary Bladder* ; Wound Healing

PURPOSE: The lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes that overcome cross-talk in nonmuscle invasive low grade (LG)-urothelial carcinoma (UC) of the bladder is a clinical limitation in the use of mTOR inhibitor for the treatment of UC. MATERIALS AND METHODS: Presently, gene expression patterns, gene ontology, and gene clustering by dual (p70S6K and S6K) siRNAs or rapamycin in 253J and TR4 cell lines were investigated by microarray analysis. mTOR/S6K pathway downstream genes suppressed to siRNAs, and rapamycin up-regulated or rapamycin down-regulated genes were identified. The mTOR downstream genes examined using a tissue microarray of 90 nonmuscle invasive LG-UC patients to assess whether any of these genes predicted clinical outcomes. A knockout study evaluated the synergistic effect with rapamycin. RESULTS: In the microarray analysis, mTOR pathway downstream genes selected consisted of 4 rapamycin down-regulated (FOXM1, KIF14, MYBL2, and UHRF1), and 4 rapamycin up-regulated (GPR87, NBR1, VASH1, and PRIMA1). In the tissue microarray, FOXM1, KIF14, and NBR1 were more expressed at T1, and MYBL2, and PRIMA1 were more expressed in tumors exceeding 3 cm. In a multivariate Cox regression model, KIF14 and NBR1 were significant predictors of recurrence in nonmuscle invasive LG-UC of the bladder. In a NBR1 knock out model, rapamycin treatment synergistically inhibited cell viability and colony forming ability compared to rapamycin only. CONCLUSIONS: The results implicate KIF14 and NBR1 as mTOR/S6K pathway downstream genes that predict recurrence in nonmuscle invasive LG-UC of the bladder and demonstrate that NBR1 knockout overcomes rapamycin cross-talk.
Biomarkers ; Cell Line ; Cell Survival ; Gene Expression ; Gene Ontology ; Humans ; Microarray Analysis ; Recurrence* ; RNA, Small Interfering ; Sirolimus* ; Urinary Bladder Neoplasms ; Urinary Bladder*

There exists a need to develop strategies that promote neovascularization in virtually all tissue engineering and regenerative medicine efforts. While research typically focuses on understanding and exploiting the role of angiogenic factors and vascular cells on new blood vessel formation, the activity of the immune system is being recognized to impact vascular formation and adaptation. This review will provide both an overview of the relationship of angiogenesis and the immune system, and how biomaterials may be designed to promote favorable angiogenesis by interaction between these 2 systems to promote effective vascularization.
Angiogenesis Inducing Agents ; Biocompatible Materials ; Blood Vessels ; Immune System ; Inflammation* ; Regenerative Medicine ; Tissue Engineering

Intravesical instillation of Mycobacterium bovis bacille Calmette–Guérin (BCG) has been used for treating nonmuscle invasive bladder cancer as the forefront of immunotherapy, but BCG is ineffective in approximately 30–40% of cases and disease recurs in up to 50% of patients. Recently BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, and the genetic control of these mycobacteria is advanced in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. We will discuss current advances in recombinant BCG construction, research, and future directions.
Administration, Intravesical ; BCG Vaccine ; Humans ; Immunotherapy* ; Mycobacterium bovis ; Urinary Bladder Neoplasms* ; Urinary Bladder*