Regeneration Ability Research Articles

Extracellular vesicles (EVs): A promising therapeutic tool in the heart tissue regeneration.

Mesenchymal stem cells (MSCs) treatment has been widely explored as a therapy for myocardial infarction, peripheral ischemic vascular diseases, dilated cardiomyopathy, and pulmonary hypertension. Latest in vitro studies suggest that MSCs can differentiate into contractile cardiomyocytes. One of the best-characterized MSCs products are MSCs-derived extracellular vesicles (EVs). EVs are crucial paracrine effectors of MSCs. Based on previous works, paracrine effects of MSCs play a primary role in the regenerative ability. Hence, in the current paper, we focused our attention on an alternative approach, exploiting products derived from human dental pulp stem cells (hDPSCs) rather than MSCs themselves, which may denote a cost-effective and safer approach. The focus has been on EVs and the bioactive molecules they contain to evaluate their ability to influence the differentiation process toward cardiomyogenic lineage. The expression of GATA4, ACTC1, CX43, and Nkx2.5 was evaluated using Immunofluorescence, real time-PCR, and Western blotting analyses. Furthermore, the expression profiling analysis of the microRNA hsa-miR-200c-3p, targeting the GATA4 gene, was studied. The hsa-miR-200c-3p was found significantly down-regulated in both c-hDPSCs + EVs-hDPSCs and c-hDPSCs + EVs-HL-1 compared to untreated c-hDPSCs underlying a possible epigenetic mechanism behind the prevalent up-regulation of its targeted GATA4 gene. The aim of the present work was to develop an in vitro model of hDPSCs able to differentiate into cardiomyocytes in order to investigate the role of EVs derived from hDPSCs and derived from HL-1 cardiomyocyte cell line in modulating the differentiation process toward cardiomyogenic lineage.

PCAT-1' s role in wound healing impairment: Mitochondrial dysfunction and bone marrow stem cell differentiation inhibition via PKM2/β-catenin pathway and its impact on implant osseo-integration.

This study focused on unravelling the role of PCAT-1 in wound-healing process, particularly its impact on regenerative and osteogenic abilities of mesenchymal stem cells (MSCs). We delved into how PCAT-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) and interacts with pivotal molecular pathways, especially β-catenin and PKM2, using human bone marrow-derived MSCs. MSCs were cultured under specific conditions and PCAT-1 expression was modified through transfection. We thoroughly assessed several critical parameters: MSC proliferation, mitochondrial functionality, ATP production and expression of wound healing and osteogenic differentiation markers. Further, we evaluated alkaline phosphatase (ALP) activity and mineral deposition, essential for bone healing. Our findings revealed that overexpressing PCAT-1 significantly reduced MSC proliferation, hampered mitochondrial performance and lowered ATP levels, suggesting the clear inhibitory effect of PCAT-1 on these vital wound-healing processes. Additionally, PCAT-1 overexpression notably decreased ALP activity and calcium accumulation in MSCs, crucial for effective bone regeneration. This overexpression also led to the reduction in osteogenic marker expression, indicating suppression of osteogenic differentiation, essential in wound-healing scenarios. Moreover, our study uncovered a direct interaction between PCAT-1 and the PKM2/β-catenin pathway, where PCAT-1 overexpression intensified PKM2 activity while inhibiting β-catenin, thereby adversely affecting osteogenesis. This research thus highlights PCAT-1's significant role in impairing wound healing, offering insights into the molecular mechanisms that may guide future therapeutic strategies for enhancing wound repair and bone regeneration.

Augmented wound healing potential of photosensitive GelMA hydrogel incorporating antimicrobial peptides and MXene nanoparticles.

Introduction: Wound healing is a delicate and complex process influenced by many factors. The treatment of skin wounds commonly involves the use of wound dressings, which remain a routine approach. An ideal dressing can provide protection and a suitable environment for wound surfaces by maintaining moisture and exhibiting good biocompatibility, mechanical strength, and antibacterial properties to promote healing and prevent infection. Methods: We encapsulated tick-derived antibacterial polypeptides (Os) as a model drug within a methylacrylyl gelatin (GelMA) hydrogel containing MXene nanoparticles. The prepared composite hydrogels were evaluated for their wound dressing potential by analyzing surface morphology, mechanical properties, swelling behavior, degradation properties, antibacterial activity, and cytocompatibility. Results: The results demonstrated excellent mechanical strength, swelling performance, degradation behavior, and antibacterial activity of the prepared composite hydrogels, effectively promoting cell growth, adhesion, and expression of antibacterial peptide activity. A full-thickness rat wound model then observed the wound healing process and surface interactions between the composite hydrogels and wounds. The composite hydrogel significantly accelerated wound closure, reduced inflammation, and sped epithelial formation and maturation. Discussion: Incorporating antibacterial peptides into GelMA provides a feasible strategy for developing excellent antibacterial wound dressings capable of tissue repair. In conclusion, this study presents a GelMA-based approach for designing antibacterial dressings with strong tissue regenerative ability.

Morphohistological study of regeneration of knee joint cartilage defects in an experimental model under the influence of nuclear magnetic resonance therapy

Despite the variety of modern methods of treatment, the problem of hyaline cartilage regeneration is still relevant. Purpose of the study: to determine the effect of nuclear magnetic resonance therapy on the regenerative ability of simulated defects in the cartilage tissue of the knee joint in rats, to assess the dynamics of microscopic changes in articular cartilage in the main and control groups. The study was performed on 60 sex-mature rats. The defects were created in the area of the articular surfaces of the left knee joint – 30 defects in the main group and 30 defects in the control group. The right knee joint of both study groups was used as the norm. Medical (antibiotics, anti-inflammatory, analgesic) therapy was carried out for 3 days after the surgery. On the 4th day after surgery, rats of the main group were given nuclear magnetic resonance therapy for 60 minutes, for 7 days. After 7, 14, 21, 28 days after therapy, histological analysis of cartilage regenerate was performed. 28 days after the use of nuclear magnetic resonance therapy, the height of cartilage regenerate in rats was 82.12±8.89 μm in the intervention group and 56.34±7.82 μm in the control group. Cartilage regenerate in rats after nuclear magnetic resonance therapy was close to the structure of intact hyaline cartilage. However, complete regeneration did not occur, as evidenced by the smaller thickness of the articular cartilage compared to that in the right knee joint. In the control group, the formation of the regeneration had pronounced signs of dysregeneration. The cartilage tissue in the area of the defect, was predominantly fibrous in the nature with areas of necrosis. Nuclear magnetic resonance therapy contributes to the formation of articular cartilage in the defect – cartilage regenerate, which in its histological structure approaches hyaline cartilage.

Efficient removal of aqueous Pb(II) ions by magnetic alginate composite microcapsules containing canola straw‐derived biochar as the reinforcing fillers

AbstractWith the rapid development of industry, water pollution caused by lead has caused great harm to human health. In this study, alginate is used as a base and blended with biochar to form calcium alginate hydrogel beads with high mechanical properties through ionic cross‐linking. Besides, the material (BC/MCAC) is prepared by the material (C‐γ‐Fe2O3) as a magnetizing agent and to remove lead. Then, a series of batch experiments and material characterizations are performed to evaluate the adsorption process of the material. The results show that the maximum adsorption capacity of BC/MCAC to Pb(II) is 211.6 mg g−1 at pH = 7. The adsorption process is well described by the Langmuir adsorption isotherm and pseudo‐second‐order kinetic model. This indicates that the lead adsorbed by BC/MCAC is a monolayer chemisorption that occurs on a uniform surface. After three regeneration cycles, BC/MCAC is found to retain 82.37% of the lead adsorption capacity and has good regeneration ability. Lead is removed by BC/MCAC mainly through the complexation of oxygen‐containing functional groups, electrostatic interaction, and ion exchange. BC/MCAC allows for more sustainable use of the wastes and is expected to be a new type of lead adsorbent for industrial wastewater.

Natural Anticancer Peptides from Marine Animal Species: Evidence from In Vitro Cell Model Systems.

Anticancer peptides are short and structurally heterogeneous aminoacidic chains, which display selective cytotoxicity mostly against tumor cells, but not healthy cells, based on their different cell surface properties. Their anti-tumoral activity is carried out through interference with intracellular homeostasis, such as plasmalemma integrity, cell cycle control, enzymatic activities and mitochondrial functions, ultimately acting as angiogenesis-, drug resistance- and metastasis-inhibiting agents, immune stimulators, differentiation inducers and necrosis or extrinsic/intrinsic apoptosis promoters. The marine environment features an ever-growing level of biodiversity, and seas and oceans are poorly exploited mines in terms of natural products of biomedical interest. Adaptation processes to extreme and competitive environmental conditions led marine species to produce unique metabolites as a chemical strategy to allow inter-individual signalization and ensure survival against predators, infectious agents or UV radiation. These natural metabolites have found broad use in various applications in healthcare management, due to their anticancer, anti-angiogenic, anti-inflammatory and regeneration abilities. The aim of this review is to pick selected studies that report on the isolation of marine animal-derived peptides and the identification of their anticancer activity in in vitro cultures of cancer cells, and list them with respect to the taxonomical hierarchy of the source organism.

Biomimetic Injectable Hydrogel Based on Methacrylate-Modified Silk Fibroin Embedded with Kartogenin for Superficial Cartilage Regeneration.

The weak regeneration ability of chondrocytes is one of the main reasons that limit the therapeutic effect of clinical cartilage injury. Injectable hydrogels are potential scaffolds for cartilage tissue engineering with advantages such as minimally invasive surgery, porous structure, and drug sustained-release ability. At present, many biomaterials have been developed for the repair of deep cartilage defects. However, cartilage injury often begins on the surface, which requires us to propose a treatment strategy suitable for superficial cartilage injury repair. In this study, we fabricated a biomimetic injectable hydrogel based on methacrylate-modified silk fibroin (SilMA) embedded with kartogenin (KGN). The SilMA/KGN hydrogels have good biohistocompatibility and the ability to promote cartilage differentiation. In addition, SEM results show that it has a porous structure conducive to cell adhesion and proliferation. Most importantly, it has demonstrated remarkable superficial cartilage repair ability in vivo, showing potential in cartilage tissue engineering.

Unraveling Epigenetic Changes in A. thaliana Calli: Impact of HDAC Inhibitors.

The ability for plant regeneration from dedifferentiated cells opens up the possibility for molecular bioengineering to produce crops with desirable traits. Developmental and environmental signals that control cell totipotency are regulated by gene expression via dynamic chromatin remodeling. Using a mass spectrometry-based approach, we investigated epigenetic changes to the histone proteins during callus formation from roots and shoots of Arabidopsis thaliana seedlings. Increased levels of the histone H3.3 variant were found to be the major and most prominent feature of 20-day calli, associated with chromatin relaxation. The methylation status in root- and shoot-derived calli reached the same level during long-term propagation, whereas differences in acetylation levels provided a long-lasting imprint of root and shoot origin. On the other hand, epigenetic signs of origin completely disappeared during 20 days of calli propagation in the presence of histone deacetylase inhibitors (HDACi), sodium butyrate, and trichostatin A. Each HDACi affected the state of post-translational histone modifications in a specific manner; NaB-treated calli were epigenetically more similar to root-derived calli, and TSA-treated calli resembled shoot-derived calli.

Effect of Pruning Treatment on Growth Characteristics and Metabolites in Eucommia ulmoides Oliver (E. ulmoides)

The effect of pruning treatments on growth, photosynthesis characteristics, and metabolites were was studied in Eucommia ulmoides Oliver (E. ulmoides). The experiment was carried out from March–August 2019. Three treatments were used: non-pruned trees (CK), a height of 20 cm above the top edge of the flowerpot (T1), and a height of 10 cm above the top edge of the flowerpot (T2). The results showed that the branches branch number, leaves leaf number, and stem diameter increased significantly (p < 0.05) in pruning treatments compared with CK. Similarly, the net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), maximum photosynthetic efficiency (Fv/Fm), and non-photochemical quenching coefficient (NPQ) increased significantly in pruning treatments (p < 0.05). Interestingly, the contents of Chl a, Chl b, Chl, Car, and the rate between the Chl a content and the Chl b content increased significantly (p < 0.05) in T2, respectively. These verified that it was a better way to enhance the plants growth of E. ulmoides for pruning treatments. The GC-MS analysis showed that 36 different primary metabolites were identified, including 11 sugars, 13 acids, 5 alcohols, and 7 other compounds, the relative content of their metabolites were was higher in the T2 treatment than that in the T1 treatment, which was mainly concentrated in four main enrichment pathways (Galactose metabolism; Citrate cycle; Glyoxylate and dicarboxylate metabolism; and starch and sucrose metabolism) via KEGG analysis. Meanwhile, correlation analysis showed there were was a positive correlation between the accumulation of D-Galactose, D-Mannose, Succinic acid, and photosynthetic pigment content, and the rate of photosynthesis in T2 treatment (p < 0.05). The pruning height above the top edge of the flowerpot changed the accumulation of primary metabolites and promoted plant regeneration ability in E. ulmoides. Finally, the yield of main secondary metabolites from leaves (Genipin, Geniposide, Geniposidic acid, and Pinoresinol diglucoside) were was increased in pruning treatments by UPLC analysis. It provided a reference for the directional ecological cultivation of E. ulmoides.

Poly(lactic acid/caprolactone) bilayer membrane achieves bone regeneration through a prolonged barrier function.

Guided bone regeneration (GBR) is a treatment strategy used to recover bone volume. Barrier membranes are a key component of GBR protocols, and their properties can impact treatment outcomes. This study investigated the efficacy of an experimental, slow-degrading, bilayer barrier membrane for application in GBR using in vivo animal models. A synthetic copolymer of poly(lactic acid/caprolactone) (PLCL) was used to prepare a slow-degrading bilayer membrane. The biodegradability of PLCL was evaluated by subcutaneous implantation in a rat model. The barrier function of the PLCL membrane was investigated in a rat calvaria defect model and compared with commercially available membranes composed of type I collagen (Col) and poly(lactic-co-glycolic acid) (PLGA). An alveolar bone defect model in beagle dogs was used to simulate GBR protocols to evaluate the bone regeneration ability of the experimental PLCL membrane. The PLCL membrane showed slow biodegradation, resulting in an efficient and prolonged barrier function compared with commercial materials. In turn, this barrier function enabled the space-making ability of PLCL membrane and facilitated bone regeneration. In the alveolar bone defect model, significantly greater regeneration was achieved by treatment with PLCL membrane compared with Col and PLGA membranes. Additionally, a continuous alveolar ridge contour was observed in PLCL-treated bone defects. In conclusion, the PLCL bilayer membrane is a promising biomaterial for use in GBR given its slow degradation and prolonged barrier function.

Recent advances and future prospects in direct cardiac reprogramming.

Cardiovascular disease remains a leading cause of death worldwide despite important advances in modern medical and surgical therapies. As human adult cardiomyocytes have limited regenerative ability, cardiomyocytes lost after myocardial infarction are replaced by fibrotic scar tissue, leading to cardiac dysfunction and heart failure. To replace lost cardiomyocytes, a promising approach is direct cardiac reprogramming, in which cardiac fibroblasts are transdifferentiated into induced cardiomyocyte-like cells (iCMs). Here we review cardiac reprogramming cocktails (including transcription factors, microRNAs and small molecules) that mediate iCM generation. We also highlight mechanistic studies exploring the barriers to and facilitators of this process. We then review recent progress in iCM reprogramming, with a focus on single-cell '-omics' research. Finally, we discuss obstacles to clinical application.

INTERRELATION RECURRENCE RATE OF CHEILITIS FROM THE LEVELS OF VITAMIN D

Vitamin D deficiency is a widespread problem among carriers, people living in acute lack of sunlight in northern latitude regions, this is the result of low serum concentrations of the vitamin. Chronic lip fissure and meteorological cheilitis are the most common forms of cheilitis among residents of the Far North. The role of vitamin D deficiency has not been studied in patients with these diagnoses. The purpose of the study is to measure the level of vitamin D in the blood serum in patients with chronic lip fissure and meteorological cheilitis, as well as to dynamically study the dependence cases of disease recurrence on the concentration vitamin D. The study was conducted in 79 residents of the Murmansk region for 12 months. Diagnostic results have established that low serum vitamin D concentrations support the recurrence of meteorological cheilitis and chronic cleft lip. The use of vitamin D to maintain a normal level of vitamin in the blood serum improves the regenerative ability of the lip skin, maintains the barrier function of the epithelium, and reduces cheilitis recurrence rate. The study found that in the conditions of the Far North one of the mandatory components of the prevention and pathogenetic therapy of meteorological cheilitis and chronic lip fissure should be vitamin therapy with cholecalciferol preparations.

In-CdS@ZIF-8&FDH photo-enzyme nanosystem with high NADH regeneration ability via indium doping for enhanced CO2 reduction to formic acid

Replacement of fossil fuel by renewable resources is a central resource and energy efficiency strategy, where CO2 is the key molecule to proceed effectively in this direction. Here, we synthesized In-doped CdS and constructed a new photo-enzyme nanosystem 10 %In-CdS@ZIF-8&FDH, which can catalyze CO2 to formic acid (HCOOH) via formate dehydrogenase immobilized on ZIF-8 while photocatalytic regenerating NADH via indium-doped CdS. Indium doping greatly enhances the photocatalytic performance of CdS. The NADH regeneration rate reaches 94.10 %. The nanosystem can produce 267.18 μM HCOOH, which is 4.27 times that of the free enzyme system. And 85.98 % of the residual activity can be retained after reusing 8 times. This study will inspire more research efforts for light-driven enzymatic nanosystems in CO2 fixation and lay the foundation for realizing renewable energy-driven CO2 conversion to produce chemical products.

Cannabidiol represses miR-143 to promote cardiomyocyte proliferation and heart regeneration after myocardial infarction

Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143–3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143–3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of Yap and Ctnnd1, which were demonstrated as the target genes of miR-143–3p. Silencing of Yap and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the cannabinoid receptor 2 impeded the regulatory effect of CBD on miR-143–3p and its downstream target Yap/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143–3p/Yap/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.

Dual-modal flexible zinc-air battery-driven self-powered and impedimetric aptasensor based on the hybrid of V2CTx MXene and bimetallic layered double hydroxide for the detection of cortisol

Based on the heterojunction of V2CTx MXene and bimetallic CoNi-layered double hydroxide (CoNi-MLDH), a novel dual-modal electrochemical aptasensor (denoted as CoNi-MLDH@V2CTx) was developed for the noninvasive point-of-care detection of cortisol in different body fluids (such as sweat, urine, and blood). Herein, V2CTx nanosheets (NSs) were used as scaffolds for the in-situ growth of cobalt/nickel zeolitic imidazolate framework (CoNi-ZIF) polyhedrons, which was then converted to CoNi-MLDH NSs through an in situ etching–coprecipitating process. Benefiting from the merits of V2CTx NSs (excellent electrochemical activity) and CoNi-ZIF (large specific surface and pore size, rich functionality, excellent oxygen reduction, and strong bioaffinity toward aptamer), and from the synergistic effect, the CoNi-LDH@V2CTx junction showed great potential as a platform for the constructing the electrochemical aptasensor for detecting cortisol. Within a wide cortisol range 10 fg mL−1 to 100 ng mL−1, the dual-modal impedimetric and zinc-air battery-driven self-powered aptasensor based on CoNi-MLDH@V2CTx illustrated the ultralow detection limit of cortisol, 0.26 and 0.17 fg mL−1, respectively. They demonstrated high selectivity, superior stability, excellent reproducibility, and promising regeneration ability, and showed potential applications for cortisol analysis in different environments (sweat, urine, and blood). The present work provides a promising option for maintaining people’s mental health through the sensitive and selective detection of cortisol in human fluids.

ПРИЖИВАЕМОСТЬ И КИНЕТИКА РОСТОВЫХ ПРОЦЕССОВ РАЗЛИЧНОГО ТИПА МИКРОЧЕРЕНКОВ ВИНОГРАДА IN VITRO

New data on the peculiarities of the growth and development of plants of the Mahrovatchik and Belobulaniy grape varieties during subcultiva-tion, depending on the location of donor micro-gears on the shoot, are presented. There are 3 types of micro gears:type 1−1–4 micro gears from the lower part of the shoot, type 2 –from the middle part, 5−8 from the base of the shoot; type 3 − from the upper part of the shoot, 9−12 from the base of the shoot. When cultivated in conditions of high temperature and low humidi-ty, the best development was noted in the plants of the Mahrovatchik variety formed from the eyes of the middle part of the shoot. Inhibi-tion of shoot growth and higher plant viability during the entire cultivation period allows us to consider type 1 (bottom) of micro-gears optimal for laying a collection, and micro-gears of the upper and middle part of the shoot to be used for mass reproduction of the Belobulaniy varie-ty. The high regenerative ability of the ripened micro-gears of the Cabernet Sauvignon variety has been proven.

An injury-responsive mmp14b enhancer is required for heart regeneration.

Mammals have limited capacity for heart regeneration, whereas zebrafish have extraordinary regeneration abilities. During zebrafish heart regeneration, endothelial cells promote cardiomyocyte cell cycle reentry and myocardial repair, but the mechanisms responsible for promoting an injury microenvironment conducive to regeneration remain incompletely defined. Here, we identify the matrix metalloproteinase Mmp14b as an essential regulator of heart regeneration. We identify a TEAD-dependent mmp14b endothelial enhancer induced by heart injury in zebrafish and mice, and we show that the enhancer is required for regeneration, supporting a role for Hippo signaling upstream of mmp14b. Last, we show that MMP-14 function in mice is important for the accumulation of Agrin, an essential regulator of neonatal mouse heart regeneration. These findings reveal mechanisms for extracellular matrix remodeling that promote heart regeneration.

Evaluation of Gelatin/Hyaluronic Acid-Generated Bridging in a 3D-Printed Titanium Cage for Bone Regeneration.

3D-printed titanium (Ti) cages present an attractive alternative for addressing issues related to osteoporosis-induced fractures, accidental fractures, and spinal fusion surgery due to disc herniation. These Ti-based bone implants possess superior strength compared to other metals, allowing for versatile applications in orthopedic scenarios. However, when used as standalone solutions, certain considerations may arise, such as interaction with soft tissues. Therefore, to overcome these issues, the combination with hydrogel has been considered. In this study, to impart Ti with regenerative abilities a 3D-printed Ti cage was loaded with gelatin and hyaluronic acid (G-H) to improve the cell attachment ability of the Ti-based bone implants. The void spaces within the mesh structure of the 3D Ti cage were filled with G-H, creating a network of micro-sized pores. The filled G-H acted as the bridge for the cells to migrate toward the large inner pores of the 3D Ti cage. Due to the microporous surface and slow release of gelatin and hyaluronic acid, the biocompatibility of the coated Ti cage was increased with an elevation in osteoconduction as depicted by the up-regulation of bone-related gene expressions. The in vivo implantation in the rabbit femur model showed enhanced bone regeneration due to the coated G-H on the Ti cage compared to the pristine hollow Ti cage. The G-H filled the large holes of the 3D Ti cage that acted as a bridge for the cells to travel inside the implant and aided in the fast regeneration of bone.

Ca/Al and Mg/Al LDH Supported on Biochars As Effective Adsorbent and Highly Regeneration Ability for Phenol Removal from Aqueous Solution

This research conducted a composite of Ca/Al and Mg/Al Layered double hydroxide with Biochar material using co-precipitation method. Characterization results were carried out with various analyses including XRD, FT-IR, and BET. The results of XRD analysis on Ca/Al-BC showed peaks at 10-11° and 22°, while the Mg/Al-BC material showed peaks at 11. 41° (003), 22. 95° (002), 34. 05° (012) and 60.2° (116). The FT-IR analysis showed that Ca/Al and Mg/Al LDH materials composited with Biochar have functional groups of -OH, nitrate ions, C=O, C-H, C-O, and M-O. BET analysis results show an increase in surface area in Ca/Al and Mg/Al LDH materials after composite with biochar from 29.333 m2/g to 158.291 m2/g in Mg/Al-BC, while in Mg/Al-BC there is an increase from 23.150 m2/g to 111.404 m2/g. The Ca/Al-BC and Mg/Al-BC composite materials have better stability than Ca/Al and Mg/Al LDH materials that can be used up to the fifth cycle. Hydrogen bonding and π-π interaction between the adsorbent and the aromatic ring on phenol can affect the adsorption process.

VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis

The liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial-cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via nonintegrative and safe nucleoside-modified mRNA encapsulated into lipid nanoparticles (mRNA-LNPs) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and elimination of steatosis and fibrosis. In human and murine diseased livers, we further identified VEGFA-receptor KDR-expressing BECs associated with KDR-expressing cell-derived hepatocytes. This work defines KDR-expressing cells, most likely being BECs, as facultative progenitors. This study reveals unexpected therapeutic benefits of VEGFA delivered via nucleoside-modified mRNA-LNP, whose safety is widely validated with COVID-19 vaccines, for harnessing BEC-driven repair to potentially treat liver diseases.