The influence of a modified p53 C-terminal peptide by using a tumor-targeting sequence on cellular apoptosis and tumor treatment.

The restoration of the function of p53 in tumors is a therapeutic strategy for the highly frequent mutation of the TP53 tumor suppressor gene. P460 is a wild-type peptide derived from the p53 C-terminus and has been proven to be capable of restoring the tumor suppressor function of p53. The poor accumulation of drugs in tumors is a serious hindrance to tumor treatment. For enhancing the activity of P460, the tumor-targeting sequence Arg-Gly-Asp-Arg (RGDR, C-end rule peptide) was introduced into the C-terminus of P460 to generate the new peptide P462. P462 presented better activity than P460 in inhibiting the proliferation of cancer cells and increasing the number of tumor cells undergoing apoptosis. Cell adhesion analysis and tumor imaging results revealed that P462 showed more specific and extensive binding with tumor cells and greater accumulation in tumors than the wild-type peptide. Importantly, treatment with P462 was more efficacious than that with P460 in vivo and was associated with considerably improved tumor-homing activity. This study highlights the importance of the roles of the tumor-homing sequence RGDR in the enhancement in cell attachment and tumor accumulation. The results of this work indicate that P462 could be a novel drug candidate for tumor treatment.

Predictive Performance of Serum ß-hCG MoM Levels for Preeclampsia Screening: A Meta-Analysis.

Objective: The aim of the present study was to investigate the predictive value of using the multiple of the median (MoM) of ß-human chorionic gonadotropin (ß-hCG) levels in patients with preeclampsia (PE) and healthy pregnant women. Methods: Electronic databases including PubMed, EBSCO, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), SinoMed, Wangfang and the Weipu Journal were searched up to May 31, 2020. Two reviewers independently selected the articles and extracted data on study characteristics, quality and results. A random-effects model was employed, and standardized mean difference and 95% confidence intervals were calculated. Twenty-one case-control studies were analyzed in the present meta-analysis, including a total of 2,266 cases and 25,872 healthy controls. Results: Women who were diagnosed with PE were found to have higher early second-trimester levels of serum ß-hCG MoM compared with healthy controls, although the levels in the first trimester were not significantly different. Ethnicity subgroup analysis demonstrated that the MoM of ß-hCG serum levels was significantly higher in PE patients in both Asian and Caucasian populations during the early second trimester. Conclusion: The MoM of ß-hCG serum levels was found to be a valuable clinical indicator for predicting PE in the early second trimester, but had little predictive value in the first trimester. However, further assessment of the predictive capacity of ß-hCG within larger, diverse populations is required.

Application of cook balloon during aorta replacement in a pregnant Marfan-syndrome patient: a case report.

BACKGROUND: Aortic dissection is a rare and emergent condition. Aortic dissection during pregnancy is not much known but it is quite lethal to both mother and infant. Earlier reports published show that clinicians conducted hysterectomies during cesarean section to avoid anticoagulant-induced uterine bleeding during the following aortic surgery. CASE PRESENTATION: A woman (38, gravida 1, para 0) in the 37th gestational week suffered an acute, severe, sharp pain in the chest and back. She was diagnosed with Standford type A aortic dissection and suspected with Marfan syndrome. An emergency cesarean section was performed immediately to deliver the baby. Since the patient was on anticoagulants during aortic replacement, so Cook balloon was inserted into the uterus to prevent postpartum hemorrhage. This helped to maintain the uterus intact. Family genetic testing showed that the patient was a carrier of FBN1 mutation which was inherited from the patient's mother, and the newborn also carried the mutation. Hence the patient was concluded to be positive for Marfan syndrome. CONCLUSION: It is important that clinicians should pay attention to the possibility of aortic dissection in a pregnant woman with chest, abdominal or back pain. In this case study, we employed Cook balloon during cesarean section to avoid anticoagulant-induced uterine bleeding during the following aortic surgery.

Effects of concentration variation on the physical properties of alginate-based substrates and cell behavior in culture.

Nowadays alginate capsules exhibit good biocompatibility and high permeability for nutrients and metabolic wastes making them appealing biomaterial for therapeutic cell encapsulation. Further study of the characteristics of alginate beads which are highly dependent on various environmental conditions to create an optimum microenvironment for cells is also critical. Thus, in this study, the effect of concentration variation on the physical properties of alginate-based beads and entrapped-cells behavior was analyzed. Results showed that the increase of Ca ions concentration brought about the decrease of the average diameter, prolongation of dissolution time, reduction of permeability and swelling, and a rise of crosslinking extent and shrinkage of capsules; while raising sodium alginate concentration had an opposite effect on the diameter and shrinkage. Moreover, the addition of gelatin enhanced the penetration and swelling and slowed down the shrinkage of capsules. And MC3T3-E1 cells enclosed in the particles in which the concentration of calcium chloride, sodium alginate and gelatin was 2.5%, 2.0% and 0.5% (w/v %) had preferable abilities of proliferation and higher expression of alkaline phosphatase. Overall, the ability to tailor this system to support in vitro growth of MC3T3-E1 cells might have significance for the future use of other cell types in regenerative medicine.

Design and Biophysical Characterization of Poly (l-Lactic) Acid Microcarriers with and without Modification of Chitosan and Nanohydroxyapatite.

Nowadays, microcarriers are widely utilized in drug delivery, defect filling, and cell culture. Also, many researchers focus on the combination of synthetic and natural polymers and bioactive ceramics to prepare composite biomaterials for tissue engineering and regeneration. In this study, three kinds of microcarriers were prepared based on physical doping and surface modification, named Poly (l-lactic) acid (PLLA), PLLA/nanohydroxyapatite (PLLA/nHA), and PLLA/nHA/Chitosan (PLLA/nHA/Ch). The physicochemical properties of the microcarriers and their functional performances in MC3T3-E1 cell culture were compared. Statistical results showed that the average diameter of PLLA microcarriers was 291.9 ± 30.7 µm, and that of PLLA/nHA and PLLA/nHA/Ch microcarriers decreased to 275.7 ± 30.6 µm and 269.4 ± 26.3 µm, respectively. The surface roughness and protein adsorption of microcarriers were enhanced with the doping of nHA and coating of chitosan. The cell-carrier cultivation stated that the PLLA/nHA microcarriers had the greatest proliferation-promoting effect, while the PLLA/nHA/Ch microcarriers performed the strongest attachment with MC3T3-E1 cells. Besides, the cells on the PLLA/nHA/Ch microcarriers exhibited optimal osteogenic expression. Generally, chitosan was found to improve microcarriers with superior characteristics in cell adhesion and differentiation, and nanohydroxyapatite was beneficial for microcarriers regarding sphericity and cell proliferation. Overall, the modified microcarriers may be considered as a promising tool for bone tissue engineering.

Three-dimensional dynamic fabrication of engineered cartilage based on chitosan/gelatin hybrid hydrogel scaffold in a spinner flask with a special designed steel frame.

Cartilage transplantation using in vitro tissue engineered cartilage is considered a promising treatment for articular cartilage defects. In this study, we assessed the advantages of adipose derived stem cells (ADSCs) combined with chitosan/gelatin hybrid hydrogel scaffolds, which acted as a cartilage biomimetic scaffold, to fabricate a tissue engineered cartilage dynamically in vitro and compared this with traditional static culture. Physical properties of the hydrogel scaffolds were evaluated and ADSCs were inoculated into the hydrogel at a density of 1×10(7) cells/mL and cultured in a spinner flask with a special designed steel framework and feed with chondrogenic inductive media for two weeks. The results showed that the average pore size, porosity, swelling rate and elasticity modulus of hybrid scaffolds with good biocompatibility were 118.25±19.51 µm, 82.60±2.34%, 361.28±0.47% and 61.2±0.16 kPa, respectively. ADSCs grew well in chitosan/gelatin hybrid scaffold and successfully differentiated into chondrocytes, showing that the scaffolds were suitable for tissue engineering applications in cartilage regeneration. Induced cells cultivated in a dynamic spinner flask with a special designed steel frame expressed more proteoglycans and the cell distribution was much more uniform with the scaffold being filled mostly with extracellular matrix produced by cells. A spinner flask with framework promoted proliferation and chondrogenic differentiation of ADSCs within chitosan/gelatin hybrid scaffolds and accelerated dynamic fabrication of cell-hydrogel constructs, which could be a selective and good method to construct tissue engineered cartilage in vitro.

Numberical simulation of fluid flow and three-dimensional expansion of tissue engineering seed cells in large scale inside a novel rotating wall hollow fiber membrane bioreactor.

Currently, RWVB (Rotating wall vessel bioreactor) combined with a microcarrier used for in vitro expansion revealed that the suspended cells attached on the microcarrier will collide with outer and inner cylinders of RWVB inevitably, which leads to harmful results to the cells. Considering this, hollow fiber (HF) membrane module treated as a cell carrier is adopted to combine with RWVB to form a novel rotating wall hollow fiber membrane bioreactor (RWHMB) to avoid aforementioned harmful collision, since the cells cultured inside this bioreactor will mainly adhere to large specific surface of hollow fiber membrane module. Prior to cell experiment, mathematical simulations concerned with flow field inside RWHMB are performed by CFD, which includes the distributions of the total pressure, velocity, and shear stress with the variation of rotating speeds and directions, as well as the radial location and diameter of hollow fiber membrane. To further confirm the feasible parameters getting from the simulation, this RWHMB is adopted to expand osteoblasts isolated from SD rats within its dynamic conditions. Cell expansion in T-flask is carried out as a negative control. The results showed that with the same rotating direction and speed of 10 rpm, inner and outer cylinders of RWHMB generated cyclical stress stimulus, which was acceptable to cell expansion and facilitated the secretion of extracellular matrix. Besides, hollow fiber membrane carrier with a diameter of 0.2 mm has an excellent biocompatibility and their radial locations presented a tiny influence on flow field inside the culture chamber.

Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells.

Hyperleptinemia is a common feature of obese women who have a higher risk of endometrial cancer than women with normal weights, and epidemiologic studies have suggested a correlation between obesity and endometrial carcinoma. Therefore, understanding of the molecular mechanism involved in leptin signaling transduction is important in endometrial cancer prevention and treatment. In this study, both isoforms of the leptin receptor (Ob-R), the long form (Ob-Rb) and short form (Ob-Ra), were detected as being expressed in six endometrial cancer cell lines with various differentiation status by western blotting, and Ob-Ra was found to be more abundant than Ob-Rb in these cells. Moreover, the expressions of both isoforms were inversely correlated with histoprognostic grading. We also showed that leptin stimulated cell proliferation and induced activations of signal transducers and activators of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK1/2), AKT, and cyclooxygenase (COX)-2 in endometrial cancer cells dose-dependently by [(3)H] thymidine incorporation assay and western blotting. Leptin-stimulation resulted in increased expression of COX-2 mRNA and prostaglandin E2 (PGE2) production of endometrial cancer cells by reverse transcription-polymerase chain reaction and enzyme immunoassay, respectively, which was effectively blocked by pharmacological inhibitors of Janus tyrosine kinase 2 (JAK2), AG490; of mitogen-activated protein kinase (MAPK) kinase, U0126; of phosphatidylinositol 3-kinase (PI3K), LY294002; and of COX-2, NS398. These results suggest that leptin promotes cell proliferation of endometrial cancer cells via the aforementioned multiple signal-transduction pathways. Leptin-induced functional activation of COX-2 is JAK2/STAT3-, MAPK/ERK-, and PI3K/AKT-dependent, indicating that COX-2 may be a critical factor of endometrial carcinogenesis in obesity.