Comparison of neurally adjusted ventilatory assist and synchronized intermittent mandatory ventilation in preterm infants after patent ductus arteriosus ligation: a retrospective study.

OBJECTIVE: This study aimed to compare the efficacy of neurally adjusted ventilatory assist (NAVA) to synchronized intermittent mandatory ventilation (SIMV) in preterm infants requiring mechanical ventilation after patent ductus arteriosus (PDA) ligation. METHODS: A retrospective analysis was conducted on intubated preterm infants who underwent PDA ligation at our hospital from July 2021 to January 2023. Infants were divided into NAVA or SIMV groups based on the ventilation mode after surgery. RESULTS: Fifty preterm infants were included. During treatment, peak inspiratory pressure (PIP) and mean airway pressure (MAP) were lower with NAVA compared to SIMV (PIP: 19.1 ± 2.9 vs. 22.4 ± 3.6 cmH2O, P < 0.001; MAP: 9.1 ± 1.8 vs. 10.9 ± 2.7 cmH2O, P = 0.002). PaO2 and PaO2/FiO2 were higher with NAVA (PaO2: 94.0 ± 11.7 vs. 84.8 ± 15.8 mmHg, P = 0.031; PaO2/FiO2: 267 [220-322] vs. 232 [186-290] mmHg, P = 0.025). Less sedation was required with NAVA (midazolam: 1.5 ± 0.5 vs. 1.1 ± 0.3 µg/kg/min, P < 0.001). CONCLUSION: Compared to SIMV, early use of NAVA post PDA ligation in preterm infants was associated with decreased PIP and MAP. Early NAVA was also associated with reduced sedation needs and improved oxygenation. However, further studies are warranted to quantify the benefits of NAVA ventilation.

Using Human Milk Fortifiers to Improve the Preoperative Nutritional Status of Infants With Non-restricted Ventricular Septal Defect.

Objective: To explore the effects of human milk fortifier (HMF) on improving the preoperative nutritional status of infants with non-restricted ventricular septal defect (VSD). Methods: A prospective randomized controlled study was conducted in a provincial hospital in China. Participants were randomly divided into an intervention group (n = 29) and a control group (n = 29). HMFs were added proportionally to the infants' feeds in the intervention group based on breastfeeding status, and the infants in the control group received exclusive breastfeeding as needed. The nutritional status of the two groups was compared 1 month after the intervention. Results: Compared with the control group, the weight, head circumference, height, albumin level, and prealbumin level of the human milk fortifier group were significantly higher 1 month after the intervention (p < 0.05). The STRONGkids score of the HMF group was significantly lower than that of the non-HMF group (p < 0.05). There was no significant difference in pneumonia, liver insufficiency, feeding intolerance, or jaundice between the two groups. Conclusion: The addition of HMFs based on the breastfeeding status of infants with non-restricted VSD can improve the preoperative nutritional status and does not increase the incidence of gastrointestinal complications. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2000041135.

Research progress on the application of framework nucleic acid in bone regeneration.

Framework nucleic acid (FNA) is a set of DNA nanostructures characterized by the framework morphology. It can design rational DNA sequences and follow the principle of complementary base pairing to construct FNA. The recent discovery of FNA constructed by DNA nanotechnology has great application potential in the field of bone regene-ration. It plays a positive role in the osteogenic differentiation of stem cells, bone regeneration, vascular regeneration, neuromodulation, immune regulation, and drug delivery. Here, we reviewed the current study findings on FNA in the field of bone regeneration.

[Tetrahedral Framework Nucleic Acids and Human Health].

In recent years, tetrahedral framework nucleic acids (tFNAs) have become a hot topic in the field of DNA nanomaterials due to their excellent mechanical, chemical and biological properties. By taking advantage of these merits, tFNAs of varied sizes and modification methods have been designed and applied in diverse fields such as regenerative medicine, biosensors, and tumor treatment to promote human health. This paper reviews the current research progress of tFNAs in human health-related fields, and the future challenges in the clinical applications of tFNAs.

Non-invasive High-Frequency Oscillatory Ventilation as Initial Respiratory Support for Preterm Infants With Respiratory Distress Syndrome.

Objectives: The aim of this study was to investigate the safety and feasibility of nHFOV as initial respiratory support in preterm infants with RDS. Methods: This study retrospectively analyzed the clinical data of 244 premature infants with RDS who were treated in our hospital from January 2016 to January 2019 and divided into the nHFOV group (n = 115) and the BiPAP group (n = 129) based on the initial respiratory support method. Results: Respiratory outcomes showed that the rate of NIV failure during the first 72 hours of life in the nHFOV group was significantly lower than that in the BiPAP group. The time of NIV in the nHFOV group was significantly shorter than that in the BiPAP group. The time of supplemental oxygen in the nHFOV group was significantly shorter than that in the BiPAP group. The incidence of air leakage syndrome in the nHFOV group was significantly lower than that in the BiPAP group, and the length of hospital stay of the nHFOV group was also significantly shorter than that in the BiPAP group. Although the rate of infants diagnosed with BPD was similar between the two groups, the rate of severe BPD in the nHFOV group was significantly lower than that in the BiPAP group. Conclusion: This study showed that nHFOV as initial respiratory support for preterm infants with RDS was feasible and safe compared to BiPAP. Furthermore, nHFOV can reduce the need for IMV and reduce the incidence of severe BPD and air leak syndrome.

Kayaking paddle blade compression load distribution sensing system based on optical fiber with a polydimethylsiloxane membrane.

This paper proposed a novel real-time compression load measurement system for a kayaking paddle based on optical fiber technology. The optical fiber sensor, fiber Bragg grating, is embedded in a 2 mm polydimethylsiloxane membrane, which serves as a pressure mat that can be easily attached/detached to/from the kayaking paddle. The proposed system is proposed for measuring and evaluating both handgrip loading and paddle blade load distribution during on-water kayaking, e.g., peak compression load distribution pattern and duration of the paddle blade in real time. Both indoor prototype experiment results and on-water experimental data on an expert paddler were presented to demonstrate the application potential of the proposed system.

Effect of tetrahedral DNA nanostructures on proliferation and osteo/odontogenic differentiation of dental pulp stem cells via activation of the notch signaling pathway.

Dental pulp stem cells (DPSCs) derived from the human dental pulp tissue have multiple differentiation capabilities, such as osteo/odontogenic differentiation. Therefore, DPSCs are deemed as ideal stem cell sources for tissue regeneration. As new nanomaterials based on DNA, tetrahedral DNA nanostructures (TDNs) have tremendous potential for biomedical applications. Here, the authors aimed to explore the part played by TDNs in proliferation and osteo/odontogenic differentiation of DPSCs, and attempted to investigate if these cellular responses could be driven by activating the canonical Notch signaling pathway. Upon exposure to TDNs, proliferation and osteo/odontogenic differentiation of DPSCs were dramatically enhanced, accompanied by up regulation of Notch signaling. In general, our study suggested that TDNs can significantly promote proliferation and osteo/odontogenic differentiation of DPSCs, and this remarkable discovery can be applied in tissue engineering and regenerative medicine to develop a significant and novel method for bone and dental tissue regeneration.

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug.

Liposome is a promising carrier system for delivering bioactive molecules. However, the successful delivery of pH-sensitive molecules is still limited by the intrinsic instability of payloads in physiological environment. Herein, we developed a special liposome system that possesses an acidic micro-environment in the internal aqueous chamber to improve the chemical stability of pH-sensitive payloads. Curcumin-loaded liposomes (Cur-LPs) with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared. These Cur-LPs have similar particle size of 300 nm, comparable physical stabilities and analogous in vitro release profiles. Interestingly, the chemical stability of liposomal curcumin in 50% fetal bovine serum and its anticancer efficacy in vitro are both micro-environmental pH-dependent (Cur-LP-2.5 > Cur-LP-5.0 > Cur-LP-7.4). This serum stability still has space to be further enhanced to improve the applicability of Cur-LP. In conclusion, creating an acidic micro-environment in the internal chamber of liposome is feasible and efficient to improve the chemical stability of pH-sensitive payloads.

Effect of tetrahedral DNA nanostructures on osteogenic differentiation of mesenchymal stem cells via activation of the Wnt/ß-catenin signaling pathway.

Adipose-derived stem cells (ADSCs) are considered to be ideal stem cell sources for bone regeneration owing to their ability to differentiate into osteo-like cells. Therefore, they have attracted increasing attention in recent years. Tetrahedral DNA nanostructures (TDNs), a new type of DNA-based biomaterials, have shown great potential for biomedical applications. In the present work, we aimed to investigate the role played by TDNs in osteogenic differentiation and proliferation of ADSCs and tried to explore if the canonical Wnt signal pathway could be the vital biological mechanism driving these cellular responses. Upon exposure to TDNs, ADSCs proliferation and osteogenic differentiation were significantly enhanced, accompanied by the up-regulation of genes correlated with the Wnt/ß-catenin pathway. In conclusion, our results indicate that TDNs are crucial regulators of the increase in osteogenic potential and ADSCs proliferation, and this noteworthy discovery could provide a promising novel approach toward ADSCs-based bone defect regeneration.

Understanding the Biomedical Effects of the Self-Assembled Tetrahedral DNA Nanostructure on Living Cells.

Recently, much attention has been paid to DNA again due to the successful synthesis of DNA-based nanostructures that can enter cells via endocytosis and thus have great potential in biomedical fields. However, the impacts of DNA nanostructures on life activities of a living cell are unknown. Herein, the promotion effect of tetrahedral DNA nanostructure (TDN) on cell growth and the underlying molecular mechanisms are reported. Upon exposure to TDN, cell proliferation is significantly enhanced, accompanied by up-regulation of cyclin-dependent kinase like-1 gene, changes in cell cycle distribution, and up-regulation of the Wnt/ß-catenin signaling-related proteins (ß-catenin, Lef 1 and cyclin D). In contrast, single-stranded DNA (ssDNA) shows no such functions. Furthermore, TDN is able to reverse the inhibition effect of DKK1, a specific inhibitor for Wnt/ß-catenin pathway. Hence, the Wnt/ß-catenin pathway is the target for TDN to promote cell proliferation. The findings allow TDN to be a novel functional nanomaterial that has great potential in tissue repair and regeneration medicine.

Insight into the Interaction of Graphene Oxide with Serum Proteins and the Impact of the Degree of Reduction and Concentration.

As novel applied nanomaterials, both graphene oxide (GO) and its reduced form (rGO) have attracted global attention, because of their excellent properties. However, the lack of comprehensive understanding of their interactions with biomacromolecules highly limits their biomedical applications. This work aims to initiate a systematic study on the property changes of GO/rGO upon interaction with serum proteins and on how their degree of reduction and exposure concentration affect this interaction, as well as to analyze the possible biomedical impacts of the interaction. We found that the adsorption of proteins on GO/rGO occurred spontaneously and rapidly, leading to significant changes in size, zeta potential, and morphology. Compared to rGO, GO showed a higher ability in quenching intrinsic fluorescence of serum proteins in a concentration-dependent manner. The protein adsorption efficiency and the types of associated proteins varied, depending on the degree of reduction and concentration of graphene. Our findings indicate the importance of evaluating the potential protein adsorption before making use of GO/rGO in drug delivery, because the changed physicochemical properties after protein adsorption will have significant impacts on safety and effectiveness of these delivery systems. On the other hand, this interaction can also be used for the separation, purification, or delivery of certain proteins.

Independent effect of polymeric nanoparticle zeta potential/surface charge, on their cytotoxicity and affinity to cells.

OBJECTIVES: Up to now, little research has been focussed on discovering how zeta potential independently affects polymeric nanoparticle (NP) cytotoxicity. METHODS: Polymeric nanoparticles of gradient zeta potential ranging from -30 mv to +40 mv were fabricated using the same poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx) biopolymer. Interaction forces between nanoparticles and cells were measured by atomic force microscopy (AFM). Cytotoxicity of the nanoparticles to cells was investigated by using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. RESULTS: Four kinds of nanoparticle with similar sizes and gradient zeta potentials, were fabricated. Those with positive surface charges were found to be more toxic than those with negative surface charges. Positively charged nanoparticles or nanoparticles with higher 'like' charges, offered higher interaction force with cells. CONCLUSION: This work proposes a novel approach for investigating interaction between NPs and cells, and discloses the importance of controlling zeta potential in developing NPs-based formulations in the future.

Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma.

microRNAs(miRNAs) can regulate epithelial-mesenchymal transition (EMT) through transcription factors, however, little is known whether EMT transcription factors can modulate miRNAs and further induce EMT and cancer metastasis. Here we show that overexpression of Snail and Slug leads to a mesenchymal phenotype and morphology and enhances cell invasion along with stem cell properties in squamous cell carcinoma of oral tongue (OTSCC) cells. Repression of miR-101 expression by Snail and Slug is essential for Snail/Slug-induced malignant phenotypes. The suppression of miR-101 subsequently activates EZH2, the sole histone methyltransferase, inducing EMT, migration and invasion of OTSCC cells. Importantly, co-overexpression of Slug and Snail correlates with poor survival and elevated EZH2 expression in two independent patient cohorts of OTSCC specimens. These findings defined a Snail and Slug/miR-101/EZH2 pathway as a novel regulatory axis of EMT-mediated-microRNA signaling.

Enhanced biostability of nanoparticle-based drug delivery systems by albumin corona.

AIMS: The long-term efficacy of nanoparticles is limited by their rapid metabolism in tissues. In this work, we aim to enhance nanoparticle biostability by preforming a bovine serum albumin (BSA) corona. MATERIALS & METHODS: A BSA corona was formed by incubating poly-3-hydroxybutyrate-co-3-hydroxyhexanoate nanoparticles with BSA solution and confirmed by SDS-PAGE and x-ray photoelectron spectroscopy. The impacts of the BSA corona on the drug release, biostability and biodistribution of nanoparticles were investigated. RESULTS: In the presence of the BSA corona, the drug release (coumarin-6 was used as the model drug) of nanoparticles was significantly slower and their stability in liver homogenate and in organs was enhanced. CONCLUSION: Preformation of a BSA corona may be a promising approach for enhancing drug biostability and for developing long-acting nanoparticle formulations.

Nanocomplex based on biocompatible phospholipids and albumin for long-circulation applications.

Achieving long circulating delivery of nanoparticles (NPs) is important for efficient drug therapy, but it is difficult due largely to proteins adsorption (opsonization) or/and nonsufficient stability of NPs. In this present work, we aimed to address the above issues by constructing a phospholipid and BSA-based nanocomplex system, namely BSA-phospholipid NPs (BSA-PL-NPs). Combining sodium dodecyl sulfate-polyacrylamide gel electrophoresis, X-ray photoelectron spectroscopy and proteins adsorption property, we confirmed that some BSA molecules were fixed on the inner surface of BSA-PL-NPs via hydrophobic interactions and the others were located in the core area. This special configuration allowed BSA-PL-NPs to not only maintain the antiadsorption and low phagocytosis properties but also have the slow zero-order drug release and the enhanced nanostructure stability. Interestingly, we found that BSA-PL-NPs had no cytotoxicity to mouse L929 fibroblasts but could stimulate the cells' growth instead. In conclusion, BSA-PL-NPs have a great potential to be developed as a long-circulation drug delivery system, and the ready availability, biocompatibility and nontoxicity of phospholipids and albumin give this system great promise for practical use.

New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits.

Promoting new bone formation during distraction osteogenesis (DO) in elderly patients with osteoporosis is still a challenge. In this study, we investigated the effect of gene therapy using local Runt-related gene 2 on new bone formation during osteoporotic mandibular DO in rabbits. First, we successfully established a mandibular osteoporotic animal model by ovariectomizing rabbits. Second, the right mandibles of the osteoporotic rabbits were distracted after corticotomy. The distraction gap of the rabbits in Group A2 and B2 were injected with Adv-hRunx2-GFP-transfected adipose-derived stromal cells (ADSCs) and Adv-GFP-transfected ADSCs, respectively. Rabbits in Groups C2 (ovariectomized control) and D2 (sham surgery control) were injected with physiologic saline. New-generation bone tissue in the distraction gap was analyzed via plain radiographic examinations, micro-computed tomography, histological examinations, and biomechanical testing at weeks 3, 6, and 9 of the consolidation period. Results of above examinations showed that no ideal new bone formation was observed in Groups B2 and C2, but obvious ideal new bone formation was observed in Group A2 and D2. The results suggested that gene therapy using rhRunx2-modified ADSCs promoted new bone formation during osteoporotic mandibular DO and effectively compensated for the detrimental effects of systemic osteoporosis on new bone formation.

Preformed albumin corona, a protective coating for nanoparticles based drug delivery system.

The non-specific interaction between nanoparticles (NPs) and plasma proteins occurs immediately after NPs enter the blood, resulting in the formation of the protein corona that thereafter replaces the original NPs and becomes what the organs and cells really see. Consequently, the in vivo fate of NPs and the biological responses to the NPs are changed. This is one substantial reason for the two main problems of the NPs based drug delivery system, i.e. nanotoxicity and rapid clearance of NPs from the blood after intravenous injection. Here, we demonstrate the successful application of the preformed albumin corona in inhibiting the plasma proteins adsorption and decreasing the complement activation, and ultimately in prolonging the blood circulation time and reducing the toxicity of the polymeric PHBHHx NPs. Since the interaction of proteins with various nano-materials and/or -particles is ubiquitous, pre-forming albumin corona has a great potential to be a versatile strategy for optimizing the NPs based drug delivery system.

The osteogenic response of undifferentiated human adipose-derived stem cells under mechanical stimulation.

The purpose of this study was to investigate the osteogenic response of human adipose-derived stem cells (hASCs) under mechanical and/or chemical stimulation. hASCs were divided into three groups. In group A, the cells were cultured without any stimulation, in group B, the cells were induced with chemical stimulation, and in group C, the cells were induced with a combination of chemical stimulation and stretch loading. Stretch loading and chemical stimulation were applied using a four-point bending apparatus (0.5 Hz, 2,000 µÎµ, 2 h/day) and osteogenic differentiation medium, respectively. At the 1st, 2nd, 3rd, 5th and 7th day following initiation of stretch loading, we detected alkaline phosphatase activity, mRNA expression (RUNX2, ALPL, osteonectin, osteopontin and type I collagen) and protein expression (RUNX2 and osteopontin) by colorimetric assay, real-time PCR and Western blot methods, respectively. Alkaline phosphatase activity, mRNA expression and protein expression all increased in groups B and C along with the culture time, but were observed to be downregulated by the 7th day in group C (p < 0.05). Compared to group A, most of the above markers were significantly higher in groups B and C (p < 0.05). All of the above markers in group C were higher than those in group B before the 5th day (p < 0.05), except at the 1st day. These results indicated that stretch loading promoted osteogenic differentiation of hASCs and that the combination of mechanical and chemical stimulation could enhance the osteogenic capability up to the 5th day relative to chemical stimulation alone.

Pharmacokinetics and disposition of nanomedicine using biodegradable PEG/PCL polymers as drug carriers.

Micelles assembled from amphiphilic poly(ethylene glycol)/poly(-caprolactone) (PEG/PCL) copolymers are promised as safe and effective drug delivery systems. They offer the potential to achieve high solubility of hydrophobic drugs, long blood circulation time and effective delivery to target organs. These advantages contribute to their application as vehicles of a broad variation of therapeutic compounds. In this review, we discussed the safety of the copolymers, release behavior of PEG/PCL micelles in vitro, and pharmacokinetic profiles referring to the optimized fate in vascular system and targeting biodistribution.

Effects of bone morphogenetic protein 2 gene therapy on new bone formation during mandibular distraction osteogenesis at rapid rate in rabbits.

OBJECTIVE: We investigated the effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) on new bone formation during rapid-rate mandibular distraction osteogenesis. We also explored the feasibility of using local BMP-2 gene therapy to compensate for bad callus formation caused by a rapid distraction rate. STUDY DESIGN: Bone marrow mesenchymal stem cells (MSCs) from Japanese rabbits were transfected with adenovirus (adv)-BMP-2. The right mandibles of the rabbits were distracted after corticotomy. The distraction rate in group A was 0.8 mm/d. The distraction rate in group B was 2.4 mm/d, and the distraction gap was injected with adv-lacZ-transfected bone marrow MSCs. The distraction rate in group C was 2.4 mm/d, and the distraction gap was injected with adv-BMP-2-transfected bone marrow MSCs. New generation bone tissue in the distraction gap was analyzed by plain radiograph examinations, microfocus computerized tomography (micro-CT) examinations, and biomechanical tests at weeks 2, 4, and 8 of the consolidation period. RESULTS: Radiographic and micro-CT examinations showed a better bone quality in group C compared with group A at weeks 2 and 4 of the consolidation period. There was no obvious new bone formation in group B. The trabecular parameters (trabecular thickness, trabecular number, volumetric bone mineral density at tissue, and bone volume fraction) were significantly higher in group C than in group A at weeks 2 and 4. At week 8, no significant difference were detected for all parameters except trabecular number between groups A and C. All biomechanical stress parameters were significantly higher in group C than in group A at week 4, and only peak stress was significantly different at week 8. CONCLUSIONS: Gene therapy using rhBMP-2-modified MSCs promoted new bone formation during mandibular distraction osteogenesis, and effectively compensated for the detrimental effect of rapid distraction rate on new bone formation.