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1.
Singapore Med J ; 65(3): 167-175, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38527301

ABSTRACT: The fields of precision and personalised medicine have led to promising advances in tailoring treatment to individual patients. Examples include genome/molecular alteration-guided drug selection, single-patient gene therapy design and synergy-based drug combination development, and these approaches can yield substantially diverse recommendations. Therefore, it is important to define each domain and delineate their commonalities and differences in an effort to develop novel clinical trial designs, streamline workflow development, rethink regulatory considerations, create value in healthcare and economics assessments, and other factors. These and other segments are essential to recognise the diversity within these domains to accelerate their respective workflows towards practice-changing healthcare. To emphasise these points, this article elaborates on the concept of digital health and digital medicine-enabled N-of-1 medicine, which individualises combination regimen and dosing using a patient's own data. We will conclude with recommendations for consideration when developing novel workflows based on emerging digital-based platforms.


Delivery of Health Care , Precision Medicine , Humans , Clinical Trials as Topic
2.
Gels ; 10(2)2024 Feb 01.
Article En | MEDLINE | ID: mdl-38391444

Conductive hydrogels are highly attractive for biomedical applications due to their ability to mimic the electrophysiological environment of biological tissues. Although conducting polymer polythiophene-poly-(3,4-ethylenedioxythiophene) (PEDOT) and polystyrene sulfonate (PSS) alone exhibit high conductivity, the addition of other chemical compositions could further improve the electrical and mechanical properties of PEDOT:PSS, providing a more promising interface with biological tissues. Here we study the effects of incorporating crosslinking additives, such as glycerol and sodium trimetaphosphate (STMP), in developing interpenetrating PEDOT:PSS-based conductive hydrogels. The addition of glycerol at a low concentration maintained the PEDOT:PSS conductivity with enhanced wettability but decreased the mechanical stiffness. Increasing the concentration of STMP allowed sufficient physical crosslinking with PEDOT:PSS, resulting in improved hydrogel conductivity, wettability, and rheological properties without glycerol. The STMP-based PEDOT:PSS conductive hydrogels also exhibited shear-thinning behaviors, which are potentially favorable for extrusion-based 3D bioprinting applications. We demonstrate an interpenetrating conducting polymer hydrogel with tunable electrical and mechanical properties for cellular interactions and future tissue engineering applications.

3.
J Mater Chem B ; 12(7): 1854-1863, 2024 Feb 14.
Article En | MEDLINE | ID: mdl-38291979

Electrical gradients are fundamental to physiological processes including cell migration, tissue formation, organ development, and response to injury and regeneration. Current electrical modulation of cells is primarily studied under a uniform electrical field. Here we demonstrate the fabrication of conductive gradient hydrogels (CGGs) that display mechanical properties and varying local electrical gradients mimicking physiological conditions. The electrically-stimulated CGGs enhanced human mesenchymal stem cell (hMSC) viability and attachment. Cells on CGGs under electrical stimulation showed a high expression of neural progenitor markers such as Nestin, GFAP, and Sox2. More importantly, CGGs showed cell differentiation toward oligodendrocyte lineage (Oligo2) in the center of the scaffold where the electric field was uniform with a greater intensity, while cells preferred neuronal lineage (NeuN) on the edge of the scaffold on a varying electric field at lower magnitude. Our data suggest that CGGs can serve as a useful platform to study the effects of electrical gradients on stem cells and potentially provide insights on developing new neural engineering applications.


Adult Stem Cells , Hydrogels , Humans , Hydrogels/pharmacology , Cell Differentiation , Cells, Cultured , Cell Line
4.
Bioeng Transl Med ; 8(6): e10490, 2023 Nov.
Article En | MEDLINE | ID: mdl-38023718

Despite being a convenient clinical substrate for biomonitoring, saliva's widespread utilization has not yet been realized. The non-Newtonian, heterogenous, and highly viscous nature of saliva complicate the development of automated fluid handling processes that are vital for accurate diagnoses. Furthermore, conventional saliva processing methods are resource and/or time intensive precluding certain testing capabilities, with these challenges aggravated during a pandemic. The conventional approaches may also alter analyte structure, reducing application opportunities in point-of-care diagnostics. To overcome these challenges, we introduce the SHEAR saliva collection device that mechanically processes saliva, in a rapid and resource-efficient way. We demonstrate the device's impact on reducing saliva's viscosity, improving sample's uniformity, and increasing diagnostic performance of a COVID-19 rapid antigen test. Additionally, a formal user experience study revealed generally positive comments. SHEAR saliva collection device may support realization of the saliva's potential, particularly in large-scale and/or resource-limited settings for global and community diagnostics.

5.
Cell Regen ; 12(1): 21, 2023 Jul 01.
Article En | MEDLINE | ID: mdl-37391680

Electrical phenomena play an important role in numerous biological processes including cellular signaling, early embryogenesis, tissue repair and remodeling, and growth of organisms. Electrical and magnetic effects have been studied on a variety of stimulation strategies and cell types regarding cellular functions and disease treatments. In this review, we discuss recent advances in using three different stimulation strategies, namely electrical stimulation via conductive and piezoelectric materials as well as magnetic stimulation via magnetic materials, to modulate cell and tissue properties. These three strategies offer distinct stimulation routes given specific material characteristics. This review will evaluate material properties and biological response for these stimulation strategies with respect to their potential applications in neural and musculoskeletal research.

6.
Am Heart J ; 260: 34-43, 2023 06.
Article En | MEDLINE | ID: mdl-36813122

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.


Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Atrial Fibrillation/surgery , Pulmonary Veins/surgery , Prospective Studies , Heart Atria/surgery , Ethanol , Catheter Ablation/methods , Treatment Outcome , Recurrence
7.
Front Public Health ; 10: 1004910, 2022.
Article En | MEDLINE | ID: mdl-36523578

Objective: Military training-induced fatigue (MIF) often results into non-combat attrition. However, standard evaluation of MIF is unavailable. This study aimed to provide credible suggestions about MIF-evaluation. Methods: A 3-round Delphi study was performed. The authority of the experts was assessed by the authority coefficient (Aa). In round 1, categories of indicators were collected via anonymous survey of experts, then potential indicators were selected via literature search. In round 2, experts should evaluate the clinical implication, practical value, and importance of each potential indicators, or recommend new indicators based on feedback of round 1. Indicators with recommendation proportions ≥ 70% and new recommended indicators would be included in round 3 to be rated on a 5-point Likert scale. "Consensus in" was achieved when coefficient of concordance (Kendall's W) of a round was between 0.2 and 0.5 and the coefficient of variation (CV) of each aspect for an indicator was < 0.5. If round 3 could not achieve "consensus in," more rounds would be conducted iteratively based on round 3. Indicators included in the recommendation set were ultimately classified into grade I (highly recommended) or grade II (recommended) according to the mean score and CV of the aspects. Results: Twenty-three experts participated with credible authority coefficient (mean Aa = 0.733). "Consensus in" was achieved in round 3 (Kendall's W = 0.435, p < 0.001; all CV < 0.5). Round 1 recommended 10 categories with 73 indicators identified from 2,971 articles. After 3-round consultation, consensus was reached on 28 indicators focusing on the cardiovascular system (n = 4), oxygen transport system (n = 5), energy metabolism/metabolite level (n = 6), muscle/tissue damage level (n = 3), neurological function (n = 2), neuropsychological/psychological function (n = 3), endocrine function (n = 3), and exercise capacity (n = 2). Among these, 11 indicators were recommended as grade I: basic heart rate, heart-rate recovery time, heart rate variability, hemoglobin, blood lactic acid, urine protein, creatine kinase, reaction time, Borg Rating of Perceived Exertion Scale, testosterone/cortisol, and vertical jump height. Conclusion: This study developed a reliable foundation for the comprehensive evaluation of MIF among soldiers.


Military Personnel , Humans , Delphi Technique , Surveys and Questionnaires , Clinical Competence , Fatigue/etiology
8.
Bioeng Transl Med ; : e10411, 2022 Sep 29.
Article En | MEDLINE | ID: mdl-36248233

In COVID-19, fomite transmission has been shown to be a major route for the spreading of the SARS-CoV-2 virus due to its ability to remain on surfaces for extended durations. Although glove wearing can mitigate the risk of viral transmission especially on high touch points, it is not prevalent due to concerns on diversion of frontline medical resources, cross-contamination, social stigma, as well as discomfort and skin reactions derived from prolonged wearing. In this study, we developed FlexiPalm, a hand-targeted auxiliary personal protective equipment (PPE) against fomite transmission of viruses. FlexiPalm is a unique palmar-side hand protector designed to be skin-conforming and transparent, fabricated from medical-grade polyurethane transparent film material as a base substrate. It serves primarily as a barrier to microbial contamination like conventional gloves, but with augmented comfort and inconspicuousness to encourage a higher public adoption rate. Compared to conventional glove materials, FlexiPalm demonstrated enhanced mechanical durability and breathability, comparable hydrophobicity, and displayed a minimal adsorption of SARS-CoV-2 spike protein and virus-like particles (VLP). Importantly, FlexiPalm was found to bind significantly less viral protein and VLP than artificial human skin, confirming its ability to reduce viral contamination. A pilot study involving participants completing activities of daily living showed a high level of comfort and task completion, illustrating the usability and functionality of FlexiPalm. Moreover, we have demonstrated that surface modification of FlexiPalm with microtextures enables further reduction in viral adsorption, thereby enhancing its functionality. An effective implementation of FlexiPalm will bolster PPE sustainability and lead to a paradigm shift in the global management of COVID-19 and other infectious diseases in general.

9.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4333-4340, 2022 Aug.
Article Zh | MEDLINE | ID: mdl-36046859

The quality of Paeoniae Radix Alba and Paeoniae Radix Rubra is evaluated by root thickness, and paeoniflorin serves as a common quality indicator of them. However, the correlation between the content of bioactive compounds and the root size is still unclear. Therefore, this study characterized the distribution patterns and content of seven bioactive compounds including paeoniflorin in different tissues of Paeonia lactiflora roots, analyzed the correlation between the root size and the content of bioactive compounds based on the xylem-to-bark ratio, and further determined the index components for quality assessment. Nine samples of fresh P. lactiflora roots were collected from the genuine cultivation area. The distribution of bioactive compounds in different tissues on the cross-section of the root was firstly analyzed by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI). Subsequently, the content of bioactive compounds was determined in the xylems and barks of the roots by UPLC. The compounds with the largest difference between the xylem and the bark were selected by orthogonal partial least squares discriminant analysis(OPLS-DA). The results indicated that paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, gallic acid, and 1,2,3,4,6-pentagalloylglucose were significantly accumulated in the xylems, while albiflorin and catechin were mainly distributed in the barks. Paeoniflorin and albiflorin, with the largest differences in the xylem and the bark, had the highest content in the two tissues. The root diameter was positively correlated with paeoniflorin content and negatively correlated with albiflorin content. As isomers with different efficacies, paeoniflorin or albiflorin can be chosen as the quality marker corresponding to specific clinical application to launch quality classification evaluation of multi-functional Chinese medicines.


Catechin , Paeonia , Bridged-Ring Compounds , Catechin/analysis , Chromatography, High Pressure Liquid/methods , Gallic Acid/analysis , Monoterpenes/analysis , Paeonia/chemistry , Plant Roots/chemistry , Spectrometry, Mass, Electrospray Ionization
10.
Front Psychol ; 13: 961351, 2022.
Article En | MEDLINE | ID: mdl-36160583

Objective: Basic combat training (BCT) is a kind of necessary high-intensity training to help each military recruit convert into a qualified soldier. In China, both the physical fatigue and passive psychological state have been observed in new recruits during BCT. However, after same-intensity training, the degree of fatigue and passive mood vary among recruits. Therefore, this study aimed to explore the effect of BCT on mood state of recruits with different physical fitness levels from a perspective of fatigue. Materials and methods: Before and after BCT, the degree of fatigue and mood state of participants were evaluated via the Borg Rating of Perceived Exertion Scale and Profile of Mood States Questionnaire immediately after 20 push-ups as RPE and POMS scores [total mood disturbance (TMD), passive mood (Ttension, Tanger, Tfatigue, Tdepression, and Tconfusion) and positive mood (Tvigour and Testeem)]. The participants were divided into two groups according to the RPE score measured after BCT: (1) group 1: RPE score after BCT < 13 and (2) group 2: RPE score after BCT ≥ 13. Result: A total of 564 recruits were included (group 1: 456/564, 80.85%; group 2: 108/564, 19.15%). After BCT, in group 1, TMD (from 95.65 ± 17.89 to 87.52 ± 17.63) and passive mood Ttension (from 4.46 ± 3.18 to 3.79 ± 3.14), Tfatigue (from 4.94 ± 3.58 to 3.12 ± 3.04), Tdepression (from 2.86 ± 3.41 to 2.01 ± 2.75), Tconfusion (3.12 ± 2.72 to 2.42 ± 2.57) declined significantly (all within-group p < 0.001), but positive mood both increased significantly (Tvigour: from 13.21 ± 4.59 to 15.44 ± 5.42, Testeem: from 9.18 ± 3.36 to 11.04 ± 3.67; both within-group p < 0.001); while in group 2, only Tanger (from 4.27 ± 4.16 to 6.22 ± 5.94, within-group p = 0.001) and Testeem (from 8.36 ± 3.15 to 9.07 ± 3.67, within-group p = 0.031) increased significantly. Conclusion: BCT could alleviate passive mood and add to positive mood for recruits with better physical fitness, while had no ameliorative effects on or even deteriorate most of the passive mood for recruits with worse physical fitness.

11.
Nat Commun ; 13(1): 1366, 2022 03 15.
Article En | MEDLINE | ID: mdl-35292643

Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. Stem cells are a promising stroke therapeutic, but creating ideal conditions for treatment is essential. Here we developed a conductive polymer system for stem cell delivery and electrical modulation in animals. Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Increased endogenous stem cell production corresponds with improved function. Transcriptome analysis identified stanniocalcin 2 (STC2) as one of the genes most significantly upregulated by electrical stimulation. Lentiviral upregulation and downregulation of STC2 in the transplanted stem cells demonstrate that this glycoprotein is an essential mediator in the functional improvements seen with electrical modulation. Moreover, intraventricular administration of recombinant STC2 post-stroke confers functional benefits. In summation, our conductive polymer system enables electrical modulation of stem cells as a potential method to improve recovery and identify important therapeutic targets.


Rodentia , Stroke , Animals , Recovery of Function/physiology , Stem Cell Transplantation/methods , Stroke/therapy
12.
J Integr Med ; 20(4): 355-364, 2022 07.
Article En | MEDLINE | ID: mdl-35249836

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.


Stomach Neoplasms , Animals , Cell Line, Tumor , Cell Movement , Cell Proliferation , China , Gene Expression Regulation, Neoplastic , Mice , Mice, Nude , Neoplasm Invasiveness , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics
13.
Mol Cell Biochem ; 477(6): 1873-1885, 2022 Jun.
Article En | MEDLINE | ID: mdl-35338455

Renal ischemia-reperfusion (I/R) injury is one of the most common causes of chronic kidney disease (CKD). It brings unfavorable outcomes to the patients and leads to a considerable socioeconomic burden. The study of renal I/R injury is still one of the hot topics in the medical field. Ebselen is an organic selenide that attenuates I/R injury in various organs. However, its effect and related mechanism underlying renal I/R injury remains unclear. In this study, we established a rat model of renal I/R injury to study the preventive effect of ebselen on renal I/R injury and further explore the potential mechanism of its action. We found that ebselen pretreatment reduced renal dysfunction and tissue damage caused by renal I/R. In addition, ebselen enhanced autophagy and inhibited oxidative stress. Additionally, ebselen pretreatment activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The protective effect of ebselen was suppressed by autophagy inhibitor wortmannin. In conclusion, ebselen could ameliorate renal I/R injury, probably by enhancing autophagy, activating the Nrf2 signaling pathway, and reducing oxidative stress.


NF-E2-Related Factor 2 , Reperfusion Injury , Animals , Autophagy , Humans , Isoindoles/pharmacology , NF-E2-Related Factor 2/metabolism , Organoselenium Compounds , Oxidative Stress , Rats , Reperfusion Injury/metabolism
14.
ACS Biomater Sci Eng ; 7(9): 4209-4220, 2021 09 13.
Article En | MEDLINE | ID: mdl-34510904

Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.


Elastin , Guided Tissue Regeneration , Animals , Nerve Regeneration , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sciatic Nerve/surgery , Tissue Scaffolds
15.
Biomaterials ; 275: 120982, 2021 08.
Article En | MEDLINE | ID: mdl-34214785

Severe peripheral nerve injuries often result in permanent loss of function of the affected limb. Current treatments are limited by their efficacy in supporting nerve regeneration and behavioral recovery. Here we demonstrate that electrical stimulation through conductive nerve guides (CNGs) enhances the efficacy of human neural progenitor cells (hNPCs) in treating a sciatic nerve transection in rats. Electrical stimulation strengthened the therapeutic potential of NPCs by upregulating gene expression of neurotrophic factors which are critical in augmenting synaptic remodeling, nerve regeneration, and myelination. Electrically-stimulated hNPC-containing CNGs are significantly more effective in improving sensory and motor functions starting at 1-2 weeks after treatment than either treatment alone. Electrophysiology and muscle assessment demonstrated successful re-innervation of the affected target muscles in this group. Furthermore, histological analysis highlighted an increased number of regenerated nerve fibers with thicker myelination in electrically-stimulated hNPC-containing CNGs. The elevated expression of tyrosine kinase receptors (Trk) receptors, known to bind to neurotrophic factors, indicated the long-lasting effect from electrical stimulation on nerve regeneration and distal nerve re-innervation. These data suggest that electrically-enhanced stem cell-based therapy provides a regenerative rehabilitative approach to promote peripheral nerve regeneration and functional recovery.


Neural Stem Cells , Peripheral Nerve Injuries , Animals , Axons , Electric Stimulation , Humans , Nerve Regeneration , Peripheral Nerve Injuries/therapy , Polymers , Rats , Recovery of Function , Sciatic Nerve
16.
Front Genet ; 12: 783482, 2021.
Article En | MEDLINE | ID: mdl-35111199

Zinc finger-homeodomain (ZF-HD) transcription factors play an important role in the regulation of plant growth and development, as well as the regulation of stress responses. Studies on the ZF-HD family genes have been conducted in many plants, however, the characteristics of this family in apple (Malus domestica) fruit remains to be poorly understood. In this study, we identified nineteen ZF-HD family genes in apple at the whole-genome scale, which were unevenly located on ten chromosomes. These MdZF-HD genes were phylogenetically divided into two subfamilies: zinc finger-homeodomain (ZHD) and MINI ZINC FINGER (MIF), and the ZHD subfamily was further classified into five groups (ZHDI-ZHDV). Analysis of the gene structures showed that most MdZF-HD genes lack introns. Gene expression analysis indicated that nine selected MdZF-HD genes were differentially responsive to 1-MCP (1-methylcyclopropene) treatment during the postharvest storage of "Qinguan" apple fruit. Moreover, the transcripts of six genes were further validated in "Golden Delicious" apple fruit, and five genes (MdZHD1/2/6/10/11) were significantly repressed and one gene (MdZHD7) was slightly induced by ethylene treatment. These results indicated that these six MdZF-HD genes may involve in the regulation of ethylene induced ripening process of postharvest apple fruit. These findings provide new clues for further functional investigation of ZF-HD genes, such as their roles in the regulation of fruit ripening.

18.
Biochem Biophys Res Commun ; 532(1): 151-158, 2020 10 29.
Article En | MEDLINE | ID: mdl-32838965

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%-55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 µmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway.


Heme Oxygenase (Decyclizing)/metabolism , Hyperoxia/metabolism , Kidney/injuries , Kidney/metabolism , NF-E2-Related Factor 2/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control , Animals , Antioxidants/metabolism , Apoptosis , Atmospheric Pressure , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Heme Oxygenase (Decyclizing)/antagonists & inhibitors , Male , Oxidative Stress , Protoporphyrins/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/pathology , Signal Transduction
19.
Nat Biotechnol ; 38(9): 1097, 2020 Sep.
Article En | MEDLINE | ID: mdl-32341566

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

20.
Nat Biotechnol ; 38(9): 1031-1036, 2020 09.
Article En | MEDLINE | ID: mdl-32313193

Bioelectronics for modulating the nervous system have shown promise in treating neurological diseases1-3. However, their fixed dimensions cannot accommodate rapid tissue growth4,5 and may impair development6. For infants, children and adolescents, once implanted devices are outgrown, additional surgeries are often needed for device replacement, leading to repeated interventions and complications6-8. Here, we address this limitation with morphing electronics, which adapt to in vivo nerve tissue growth with minimal mechanical constraint. We design and fabricate multilayered morphing electronics, consisting of viscoplastic electrodes and a strain sensor that eliminate the stress at the interface between the electronics and growing tissue. The ability of morphing electronics to self-heal during implantation surgery allows a reconfigurable and seamless neural interface. During the fastest growth period in rats, morphing electronics caused minimal damage to the rat nerve, which grows 2.4-fold in diameter, and allowed chronic electrical stimulation and monitoring for 2 months without disruption of functional behavior. Morphing electronics offers a path toward growth-adaptive pediatric electronic medicine.


Electronics, Medical/instrumentation , Electronics, Medical/methods , Implantable Neurostimulators , Animals , Biocompatible Materials/chemistry , Polymers/chemistry , Rats , Sciatic Nerve/physiology , Viscoelastic Substances/chemistry
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