Spray drying is an effective and stable process, which has been widely used to produce pharmaceutical powders. In the traditional spray drying process, it was not quite easy to control the aggregation and the size of particles. Particularly, the preparation of polymeric particles was relatively hard compared to the preparation of food and pharmaceutical ingredients, typically organic materials of small molecular weights. In this study, modification of a conventional spray dryer was tried to use electrical charge and co-axial nozzles to prepare polymeric particles. Poly(ethylene glycol) and poly (D,L-lactide-co-glycolide) were used as the inner polymeric materials, and lactose as the outer shell materials. The results showed that electrohydrodynamic spray-dried particles had a relatively uniform size and particle morphology, and the aggregation of particles could be suppressed compared to the conventional spray-dried particles. The electrohydrodynamic spray-dried powders consisted of spherical particles of $2{\sim}5{\mu}m$ diameters.
microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.
Biodegradable and elastic poly(L-lactide-co-$\varepsilon$-caprolactone) (PLCL) was electrospun to prepare nanofibers, and N-isopropylacrylamide (NIPAAm) was then grafted onto their surfaces under aqueous conditions using $^{60}Co-{\gamma}$ irradiation. The graft yield increased with increasing irradiation dose from 5 to 10 kGy and the nanofibers showed a greater graft yield compared with the firms. SEM confirmed that the PLCL nanofibers maintained an interconnected pore structure after grafting with NIPAAm. However, overdoses of irradiation led to the excessive formation of homopolymer gels on the surface of thc PLCL nanofibers. The equilibrium swelling and deswelling ratio of the PNIPAAm-g-PLCL nanofibers (prepared with 10 kGy) was the highest among the samples, which was consistent with the graft yield results. The phase-separation characteristics of PNIPAAm in aqueous conditions conferred a unique temperature-responsive swelling behavior of PNIPAAm-g-PLCL nanofibers, showing the ability to absorb a large amount of water at < $32^{\circ}C$, and abrupt collapse when the temperature was increased to $40^{\circ}C$. In accordance with the temperature-dependent changes in swelling behavior, the release rate of indomethacin and FITC-BSA loaded in PNIPAAm-g-PLCL nanofibers by a diffusion-mediated process was regulated by the change in temperature. Both model drugs demonstrated greater release rate at $40^{\circ}C$ relative to that at $25^{\circ}C$. This approach of the temperature-controlled release of drugs from PNIPAAm-g-PLCL nanofibers using gamma-ray irradiation may be used to design drugs and protein delivery carriers in various biomedical applications.
Lee, Jae Hoon;Kam, Eun Hee;Kim, Jeong Min;Kim, So Yeon;Kim, Eun Jeong;Cheon, So Yeong;Koo, Bon-Nyeo
Biomolecules & Therapeutics
/
v.25
no.2
/
pp.149-157
/
2017
The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.
Lee, Yae Heun;Lee, Yoo Jung;Jung, Sun Young;Kim, Suk Young;Son, Dong Woo;Seo, Il Hye
Perinatology
/
v.29
no.4
/
pp.147-152
/
2018
Objective: This study examines whether maternal group B Streptococcus (Streptococcus agalactiae, GBS) infection was associated with preterm births and premature neonatal outcomes. Methods: Maternal and neonatal outcomes were examined among singleton pregnant women with preterm birth (from $24^{+0}weeks$ to $36^{+6}weeks$) who were tested for GBS (n=203) during the pregnancy. Data were collected retrospectively from the medical records of women who delivered at our hospital from January 2015 to February 2017. We compared obstetrical factors (causes of preterm birth) and neonatal (gestational age at delivery, birth weight, Apgar score 1 min/5 min, hospitalization period, duration of mechanical ventilation, neonatal C-reactive protein within three days, and other complication [respiratory distress syndrome, neonatal deaths]) outcomes between GBS-infected and non-infected pregnant women. Results: There were 203 singleton pregnant women included in the study, 25 of whom were confirmed to have a GBS infection during the pregnancy. There was no difference in neonatal outcomes by GBS status. Preterm premature rupture of membranes (pPROM), as an obstetric factor, was associated with GBS infection (P=0.022). GBS infection raised the risk of pPROM by 3.6 times (odds ratio 3.648, 95% confidence interval 1.476-9.016, P=0.005). Conclusion: GBS infection in preterm birth was associated with pPROM but did not result in adverse neonatal outcomes. Continuous attention and evaluation of GBS infection, a major cause of neonatal sepsis and pneumonia, are needed.
El Koofy, Nehal Mohamed;Rady, Hanaa Ibrahim;Abdallah, Shrouk Moataz;Bazaraa, Hafez Mahmoud;Rabie, Walaa Ahmed;El-Ayadi, Ahmed Ali
Clinical and Experimental Pediatrics
/
v.62
no.9
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pp.344-352
/
2019
Background: Ventilator dependency constitutes a major problem in the intensive care setting. Malnutrition is considered a major determinant of extubation failure, however, attention has been attracted to modulating carbon dioxide production through decreasing carbohydrate loading and increasing the percent of fat in enteral feeds. The detected interrelation between substrate oxidation and ventilation outcome became the base of several research to determine the appropriate composition of the nonprotein calories of diet in ventilated patients. Purpose: We aimed to assess the effect of high-fat dietary modification and nutritional status on ventilatory and final outcomes of pediatric intensive care. Methods: Fifty-one ventilated children (1 month to 12 years of age) with pulmonary disease who could be enterally fed, in the Cairo University Pediatric intensive care unit, were divided into 2 groups: group A included 25 patients who received isocaloric high-fat, low-carbohydrate diet; group B included 26 patients who received standard isocaloric diet. Comprehensive nutritional assessment was done for all patients. Results: Group A had a significant reduction in carbon dioxide tension, but no similar reduction in the duration or level of ventilatory support. Assisted minute ventilation was predicted by weight-for-age and caloric intake rather than the type of diet. Poor nutritional status was associated with higher mortality and lower extubation rates. Mild hypertriglyceridemia and some gastrointestinal intolerance were significant in group A, with no impact on the adequacy of energy or protein delivery. Conclusion: The high-fat enteral feeding protocol may contribute to reducing carbon dioxide tension, with mild hypertriglyceridemia and negligible gastrointestinal intolerance as potential adverse effects. Optimization of nutritional status rather than dietary modification may improve ventilatory and survival outcomes in critically ill-ventilated children.
An, Sung-Min;Kim, Min Jae;Seong, Keum-Yong;Jeong, Jea Sic;Kang, Hyeon-Gu;Kim, So Young;Kim, Da Som;Kang, Da Hee;Yang, Seung Yun;An, Beum-Soo
Toxicological Research
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v.35
no.4
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pp.395-402
/
2019
Subcutaneous adipose tissue (SAT) accumulation is a constitutional disorder resulting from metabolic syndrome. Although surgical and non-surgical methods for reducing SAT exist, patients remain non-compliant because of potential adverse effects and cost. In this study, we developed a new minimally-invasive approach to achieve SAT reduction, using a microneedle (MN) patch prepared from gelatin, which is capable of regulating fat metabolism. Four gelatin types were used: three derived from fish (SA-FG, GT-FG 220, and GT-FG 250), and one from swine (SM-PG 280). We applied gelatin-based MN patches five times over 4 weeks to rats with high-fat diet (HD)-induced obesity, and determined the resulting amount of SAT. We also investigated the histological features and determined the expression levels of fat metabolism-associated genes in SAT using hematoxylin and eosin staining and western blotting, respectively. SAT decreased following treatment with all four gelatin MN patches. Smaller adipocytes were observed in the regions treated with SA-FG, GT-FG 250, and SM-PG 280 MNs, demonstrating a decline in fat accumulation. The expression levels of fat metabolism-associated genes in the MN-treated SAT revealed that GT-FG 220 regulates fatty acid synthase (FASN) protein levels. These findings suggest that gelatin MN patches aid in decreasing the quantity of unwanted SAT by altering lipid metabolism and fat deposition.
Adejoro, Festus A.;Hassen, Abubeker;Thantsha, Mapitsi S.
Asian-Australasian Journal of Animal Sciences
/
v.32
no.7
/
pp.977-987
/
2019
Objective: The use of tannin extract and other phytochemicals as dietary additives in ruminants is becoming more popular due to their wide biological actions such as in methane mitigation, bypass of dietary protein, intestinal nematode control, among other uses. Unfortunately, some have strong astringency, low stability and bioavailability, and negatively affecting dry matter intake and digestibility. To circumvent these drawbacks, an effective delivery system may offer a promising approach to administer these extracts to the site where they are required. The objectives of this study were to encapsulate acacia tannin extract (ATE) with native starch and maltodextrin-gum arabic and to test the effect of encapsulation parameters on encapsulation efficiency, yield and morphology of the microparticles obtained as well as the effect on rumen in vitro gas production. Methods: The ATE was encapsulated with the wall materials, and the morphological features of freeze-dried microparticles were evaluated by scanning electron microscopy. The in vitro release pattern of microparticles in acetate buffer, simulating the rumen, and its effect on in vitro gas production was evaluated. Results: The morphological features revealed that maltodextrin/gum-arabic microparticles were irregular shaped, glossy and smaller, compared with those encapsulated with native starch, which were bigger, and more homogenous. Maltodextrin-gum arabic could be used up to 30% loading concentration compared with starch, which could not hold the core material beyond 15% loading capacity. Encapsulation efficiency ranged from $27.7%{\pm}6.4%$ to $48.8%{\pm}5.5%$ in starch and $56.1%{\pm}4.9%$ to $64.8%{\pm}2.8%$ in maltodextrin-gum arabic microparticles. Only a slight reduction in methane emission was recorded in encapsulated microparticles when compared with the samples containing only wall materials. Conclusion: Both encapsulated products exhibited the burst release pattern under the pH conditions and methane reduction associated with tannin was marginal. This is attributable to small loading percentages and therefore, other wall materials or encapsulation methods should be investigated.
Moss, Amy F.;Chrystal, Peter V.;Cadogan, David J.;Wilkinson, Stuart J.;Crowley, Tamsyn M.;Choct, Mingan
Animal Bioscience
/
v.34
no.3_spc
/
pp.354-362
/
2021
Broiler chickens grow rapidly, and their nutrient requirements change daily. However, broilers are fed three to five diet phases, meaning nutrients are under or oversupplied throughout production. Increasing diet phases improves production efficiency as there is less time in the production cycle that nutrients are in under or over-supply. Nevertheless, the process of administering four or more diets is costly and often impractical. New technologies are now available to blend feed to match the daily nutrient requirements of broilers. Thus, the aim of this review is to evaluate previous studies measuring the impact of increasing feed phases on nutrient utilisation and growth performance, and review recent studies taking this concept to the extreme; precision nutrition - feeding a new diet for each day of the production cycle. This review will also discuss how modern precision feeding technologies have been utilised and the potential that new technologies may bring to the poultry industry. The development of a precision nutrition regime which targets daily requirements by blending dietary components on farm is anticipated to improve the efficiency of production, reduce production cost and therefore improve sustainability of the industry. There is also potential for precision feeding technology along with precision nutrition strategies to deliver a plethora of other management and economic benefits. These include increased fluidity to cope with sudden environmental or market changes, and the ability to alter diets on a farm by farm level in a large, integrated operation. Thus, the future possibilities and practical implications for such technologies to generate a paradigm shift in feed formulation within the poultry industry to meet the rising demand for animal protein is also discussed.
Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.
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