The 16S rDNA high-throughput sequencing correlation analysis of milk and gut microbial communities in mastitis Holstein cows.

This study aimed to understand the changes in the milk and gut microbiota of dairy cows with mastitis, and to further explore the relationship between mastitis and the microbiota. In this study, we extracted microbial DNA from healthy and mastitis cows and performed high-throughput sequencing using the Illumina NovaSeq sequencing platform. OTU clustering was performed to analyze complexity, multi-sample comparisons, differences in community structure between groups, and differential analysis of species composition and abundance. The results showed that there were differences in microbial diversity and community composition in the milk and feces of normal and mastitis cows, where the diversity of microbiota decreased and species abundance increased in the mastitis group. There was a significant difference in the flora composition of the two groups of samples (P < 0.05), especially at the genus level, the difference in the milk samples was Sphingomonas (P < 0.05) and Stenotrophomonas (P < 0.05), the differences in stool samples were Alistipes (P < 0.05), Flavonifractor (P < 0.05), Agathobacter (P < 0.05) and Pygmaiobacter (P < 0.05). In conclusion, the microbiota of the udder and intestinal tissues of dairy cows suffering from mastitis will change significantly. This suggests that the development of mastitis is related to the endogenous pathway of microbial intestinal mammary glands, but the mechanisms involved need further study.

The KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling during cardiac hypertrophy in male mice.

The main hallmark of myocardial substrate metabolism in cardiac hypertrophy or heart failure is a shift from fatty acid oxidation to greater reliance on glycolysis. However, the close correlation between glycolysis and fatty acid oxidation and underlying mechanism by which causes cardiac pathological remodelling remain unclear. We confirm that KLF7 simultaneously targets the rate-limiting enzyme of glycolysis, phosphofructokinase-1, liver, and long-chain acyl-CoA dehydrogenase, a key enzyme for fatty acid oxidation. Cardiac-specific knockout and overexpression KLF7 induce adult concentric hypertrophy and infant eccentric hypertrophy by regulating glycolysis and fatty acid oxidation fluxes in male mice, respectively. Furthermore, cardiac-specific knockdown phosphofructokinase-1, liver or overexpression long-chain acyl-CoA dehydrogenase partially rescues the cardiac hypertrophy in adult male KLF7 deficient mice. Here we show that the KLF7/PFKL/ACADL axis is a critical regulatory mechanism and may provide insight into viable therapeutic concepts aimed at the modulation of cardiac metabolic balance in hypertrophied and failing heart.

Understanding Teach-Back and Teach-To-Goal Strategies Embedded in Support Calls for a Health Literacy-Sensitive Childhood Obesity Treatment Trial.

BACKGROUND: Low caregiver health literacy (HL) is related to increased obesity risk for their children. Teach-Back and Teach-to-Goal (TB/TTG) are strategies that may improve comprehension of key concepts for people who have low HL but have yet to be examined in the context of childhood obesity treatment. OBJECTIVE: This study evaluated TB/TTG strategies integrated within support calls delivered to caregivers as part of a 3-month childhood obesity intervention. METHODS: Ninety-four caregivers (60% Black, 42% high school education or less, 53% with income ≤$29,999, and 34% low HL) with overweight/obese children age 8 to 12 years enrolled in a childhood obesity intervention. Caregiver HL was assessed at baseline using the Newest Vital Sign and caregivers were dichotomized to low and adequate HL groups for analyses. Caregivers received 6 bi-weekly support calls that alternated with in-person, family sessions. Call completion rates, comprehension of key content (correct responses on TB/TTG questions), and satisfaction with support calls were evaluated. Qualitative information on call satisfaction was gathered at the 3-month time point. KEY RESULTS: Average completion rate across all calls was 62% with a mean call time of 26 minutes (no significant difference between HL groups). Caregivers had an average score of 0.90 out of 1 when evaluating overall call comprehension by scoring TB/TTG performance. Content comprehension in calls 1, 3, and 4 was significantly higher among caregivers with adequate HL relative to low HL (p < .1). Caregivers from both HL groups felt satisfied with calls [9.1 (2.0)/10-point scale] and agreed that calls helped them learn class material better [8.1 (2.7)]. Qualitatively, caregivers provided 81 (75%) positive responses (e.g., good content) and 27 (25%) negative responses (e.g., too lengthy) regarding the support calls. CONCLUSIONS: Support calls using TB/TTG strategies were feasible, well received, and should be considered for incorporation into childhood obesity interventions. [HLRP: Health Literacy Research and Practice. 2021;5(3):e208-e217.] Plain Language Summary: This study evaluated support calls that used Teach-Back and Teach-to-Goal health literacy strategies as part of a childhood obesity treatment trial. Support calls were well accepted and facilitated comprehension of the key learning objectives in caregivers, regardless of health literacy level. These strategies should be considered for incorporation into childhood obesity treatment interventions to increase uptake of main concepts.

Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

Catalytic degradation of TCE by a PVDF membrane with Pd-coated nanoscale zero-valent iron reductant.

Trichloroethylene (TCE) has serious threat to ecosystem. Fe-Pd nanoparticles (NPs) are good materials for catalytic degradation of TCE but still face severe challenges including easy fouling, agglomeration, deactivation and difficult separation and reuse etc. To overcome these drawbacks, we have constructed a novel structured PVDF/Fe-Pd NPs composite membrane with nanosized surface pores to execute the TCE degradation. Results indicate the degradation shows pseudo first-order reaction kinetics and high degradation rate in the static state degradation. Furthermore, the degradation ability can be enhanced by increasing Fe and Pd contents, the degradation temperature or decreasing the degradation pH value. However, the degradation is essentially limited by the diffusion. Thus, the cross-flow degradation is further applied to promote the diffusion. By this operating model, the degradation ability of the composite membrane can be greatly improved. More importantly, the reactants always keep the purity in the membrane surface side and can be controlled to enter the membrane pore for catalytic degradation. Thus, products can be timely discharged via the membrane pores and the side reactions between reactants and products can be largely reduced. In addition, the nanosized surface pores can also prevent the Fe-Pd NPs from being fouled. In a word, the novel composite membrane shows strong degradation ability, good stability and convenient operating ability for the TEC catalytic degradation.

A dual-transduction-integrated biosensing system to examine the 3D cell-culture for bone regeneration.

Three-dimensional (3D) cell cultures developed with living cells and scaffolds have demonstrated outstanding potential for tissue engineering and regenerative medicine applications. However, no suitable tools are available to monitor dynamically variable cell behavior in such a complex microenvironment. In particular, simultaneously assessing cell behavior, cell secretion, and the general state of a 3D culture system is of a really challenging task. This paper presents our development of a dual-transduction-integrated biosensing system that assesses electrical impedance in conjunction with imaging techniques to simultaneously investigate the 3D cell-culture for bone regeneration. First, we created models to mimic the dynamic deposition of the extracellular matrix (ECM) in 3D culture, which underwent osteogenesis by incorporating different amounts of bone-ECM components (collagen, hydroxyapatite [HAp], and hyaluronic acid [HA]) into alginate-based hydrogels. The formed models were investigated by means of electrical impedance spectroscopy (EIS), with the results showing that the impedances increased linearly with collagen and hyaluronan, but changed in a more complex manner with HAp. Thereafter, we created two models that consisted of primary osteoblast cells (OBs), which expressed the enhanced green fluorescent protein (EGFP), and 4T1 cells, which secreted the EGFP-HA, in the alginate hydrogel. We found the capacitance (associated with impedance and measured by EIS) increased with the increases in initial embedded OBs, and also confirmed the cell proliferation over 3 days with the EGFP signal as monitored by the fluorescent imaging component in our system. Interestingly, the change in capacitance is found to be associated with OB migration following stimulation. Also, we show higher capacitance in 4T1 cells that secret HA when compared to control 4T1 cells after a 3-day culture. Taken together, we demonstrate that our biosensing system is able to investigate the dynamic process of 3D culture in a non-invasive and real-time manner.

Bioengineered tumor microenvironments with naked mole rats high-molecular-weight hyaluronan induces apoptosis in breast cancer cells.

The naked mole rat (nmr) is cancer resistant due to the abundant production of extremely high-molecular-weight hyaluronan (EHMW-HA). However, whether EHMW-HA has similar anti-cancer effects in mice and humans remains to be determined. The present study used breast cancer cells to clarify the effect of EHMW-HA on breast cancer. First, the overexpression of nmrHas2 in 4T1 and BT549 cell lines in both two-dimensional (2D) and three-dimensional (3D) models to mimic tumor microenvironment was established. The 4T1/BT549-nmrHas2 cells could secrete EHMW-HA (with a molecular weight of up to 6 MDa), which was similar to that found in the naked mole rat. Second, EHMW-HA altering tumor microenvironment in both 2D monolayers and 3D spheroids significantly enhanced apoptosis, inhibiting the proliferation of 4T1 and BT549 cells. The prominent anticancer effects of EHMW-HA on the cancer-cell apoptosis phenotype were further confirmed by inhibiting tumor formation in nude mice. Finally, EHMW-HA significantly induced higher p53 protein expression, which enhanced pro-apoptotic proteins p21 and Bax in breast cancer cells; this is in contrast with the triggering of hypersensitivity of the naked mole rat cells to early contact inhibition (ECI). These results have important implications for the design of therapeutic approaches based on the application of EHMW-HA.

Participatory development and pilot testing of iChoose: an adaptation of an evidence-based paediatric weight management program for community implementation.

BACKGROUND: To describe the identification, adaptation, and testing of an evidence-based pediatric weight management program for a health disparate community. METHODS: A community advisory board (CAB) of decision-makers and staff from local health care, public health, and recreation organizations engaged with academic partners to select an evidence-based program (EBP) for local implementation. Three EBPs were identified (Traffic Light, Bright Bodies, Golan and colleagues Home Environmental Model) and each EBP was rated on program characteristics, implementation and adaptation, and adoptability. Following selection of the EBP that was rated highest, the POPS-CAB made adaptations based on the program principles described in peer-reviewed publications. The adapted intervention, iChoose, was then pilot tested in 3 iterative phases delivered initially by research partners, then co-delivered by research and community partners, then delivered by community partners. The RE-AIM framework was used to plan and evaluate the iChoose intervention across all waves with assessments at baseline, post program (3 months), and follow-up (6 months). RESULTS: Bright Bodies rated highest on program characteristics and adoptability (p's < 0.05), while Home Environmental Model rated highest on implementation factors (p < 0.05). Qualitatively, the selection focused on important program characteristics and on matching those characteristics to the potential to fit within the community partner services. The adapted program-iChoose-had 18% reach and with participants that were representative of the target population on age, gender, ethnicity, and race. Effectiveness was demonstrated by modest, but significant reductions in BMI z-scores at post-program compared to baseline (MΔ = - 0.047; t = - 2.11, p = 0.046). This decrease returned to values similar to baseline 3 months (MΔ = 0.009) after the program was completed. Implementation fidelity was high and implementation fidelity did not differ between community or research delivery agents. CONCLUSION: The process to help organizations identify and select evidence-based programs appropriate for their community led to consensus on a single EBP. While iChoose was successful in initiating changes in BMI z-scores, could be implemented in a low resource community with fidelity, it was insufficient to lead to sustained child BMI z-scores. In response to these data, maintenance of program effects and delivery are the current focus of the CBPR team.

From Bright Bodies to iChoose: Using a CBPR Approach to Develop Childhood Obesity Intervention Materials for Rural Virginia.

This community-based participatory research (CBPR) project used a collaborative process to develop a culturally relevant workbook for parents of overweight children. We followed a mixed methods iterative process to assess clear communication using a CBPR approach. Materials were evaluated using readability tests, the Clear Communication Index (CCI), and the Suitability Assessment of Materials (SAM). In addition, we used surveys and focus groups to investigate parents' perceptions and gather feedback from delivery staff using the workbook. While workbook materials maintained adequate grade reading levels, our iterative process and the use of CCI and SAM led to significant improvements in (a) clearly communicating the objectives of the program, (b) being culturally relevant, and (c) reaching a high satisfaction among users. These findings suggest that evaluative measures for written materials should move beyond readability and need to account for level of clarity and cultural appropriateness of messages. Furthermore, we found that that an iterative process to intervention's material development using clear communication strategies while involving community members, parents, and research partners can lead to workbook materials that are culturally relevant to the target audience, and better communicate program objectives. Finally, this is a potentially generalizable process for improving clear communication of written health information materials.

An Intelligent Neural Stem Cell Delivery System for Neurodegenerative Diseases Treatment.

Transplanted stem cells constitute a new therapeutic strategy for the treatment of neurological disorders. Emerging evidence indicates that a negative microenvironment, particularly one characterized by the acute inflammation/immune response caused by physical injuries or transplanted stem cells, severely impacts the survival of transplanted stem cells. In this study, to avoid the influence of the increased inflammation following physical injuries, an intelligent, double-layer, alginate hydrogel system is designed. This system fosters the matrix metalloproeinases (MMP) secreted by transplanted stem cell reactions with MMP peptide grafted on the inner layer and destroys the structure of the inner hydrogel layer during the inflammatory storm. Meanwhile, the optimum concentration of the arginine-glycine-aspartate (RGD) peptide is also immobilized to the inner hydrogels to obtain more stem cells before arriving to the outer hydrogel layer. It is found that blocking Cripto-1, which promotes embryonic stem cell differentiation to dopamine neurons, also accelerates this process in neural stem cells. More interesting is the fact that neural stem cell differentiation can be conducted in astrocyte-differentiation medium without other treatments. In addition, the system can be adjusted according to the different parameters of transplanted stem cells and can expand on the clinical application of stem cells in the treatment of this neurological disorder.

A 3-year observation of testosterone deficiency in Chinese patients with chronic heart failure.

Testosterone deficiency is present in a certain proportion men with chronic heart failure (CHF). Low testosterone levels in American and European patients with CHF lead to the high mortality and readmission rates. Interestingly, this relationship has not been studied in Chinese patients. To this end, 167 Chinese men with CHF underwent clinical and laboratory evaluations associated with determinations of testosterone levels. Total testosterone (TT) levels and sex hormone-binding globulin were measured by chemiluminescence or immunoassays assays and free testosterone (FT) levels were calculated, Based upon results from these assays, patients were divided into either a low testosterone (LT; n = 93) or normal testosterone (NT; n = 74) group. Subsequently, records from each patient were reviewed over a follow-up duration of at least 3 years. Patients in the LT group experienced worse cardiac function and a higher prevalence of etiology (ischemic vs. no ischemic) and comorbidity (both P < 0.05). In addition, readmission rates of patients in the LT group were higher than that of patients in the NT group (3.32 ± 1.66 VS 1.57 ± 0.89). Overall, deficiencies in FT levels were accompanied with increased mortalities (HR = 6.301, 95% CI 3.187-12.459, P < .0001).

Modulating Three-Dimensional Microenvironment with Hyaluronan of Different Molecular Weights Alters Breast Cancer Cell Invasion Behavior.

Hyaluronan (HA), a polymer with various molecular weights (MW) found in tumor microenvironments, is associated with malignant progression of breast cancer. Reducing the amount of high-MW HA in the microenvironment by hyaluronidase is a promising approach for breast cancer treatment. However, whether the generation of HA fragments negatively affects breast cancer cells remains to be determined. Furthermore, HA forms three-dimensional (3D) networks by cross-linking with other extracellular molecules to function. Therefore, a model mimicking the cross-linked HA network is required to determine the effect of HA fragments on breast cancer cells. To clarify the differential roles of low (HA35) versus high (HA117) MW HA on cancer cell phenotype, a 3D culture system was set up by covalently cross-linking HA with alginate and investigating the behavior of 4T-1 and SKBR3 breast cancer cells alongside a two-dimensional (2D) control. The results show the invasion and migration abilities of 4T-1 and SKBR3 cells are significantly enhanced by the presence of HA35 but inhibited by HA117 in both 2D monolayers and 3D spheroids. The differential effects of HA35 and HA117 on cancer cell epithelial-mesenchymal transition (EMT) phenotype were further confirmed in terms of differential regulation of E-cadherin and vimentin as important EMT markers at both the cellular and mRNA levels. Additional experiments show the CD44-Twist signaling pathway might be involved in the differential effects of HA35 and HA117. These results have important implications with respect to understanding the role of HA in breast cancer development and for the design of therapeutic approaches based on the eradication of HA with hyaluronidase.

Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-ß signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses.

A novel double-targeted nondrug delivery system for targeting cancer stem cells.

Instead of killing cancer stem cells (CSCs), the conventional chemotherapy used for cancer treatment promotes the enrichment of CSCs, which are responsible for tumor growth, metastasis, and recurrence. However, most therapeutic agents are only able to kill a small proportion of CSCs by targeting one or two cell surface markers or dysregulated CSC pathways, which are usually shared with normal stem cells (NSCs). In this study, we developed a novel nondrug delivery system for the dual targeting of CSCs by conjugating hyaluronic acid (HA) and grafting the doublecortin-like kinase 1 (DCLK1) monoclonal antibody to the surface of poly(ethylene glycol) (PEG)-poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which can specifically target CD44 receptors and the DCLK1 surface marker - the latter was shown to possess the capacity to distinguish between CSCSs and NSCs. The size and morphology of these NPs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). This was followed by studies of NP encapsulation efficiency and in vitro drug release properties. Then, the cytotoxicity of the NPs was tested via Cell Counting Kit-8 assay. Finally, the 4T1 CSCs were obtained from the alginate-based platform, which we developed as an in vitro tumor model. Tumor-bearing nude mice were used as in vivo models to systematically detect the ability of NPs to target CSCs. Our results showed that the DCLK1-HA-PEG-PLGA NPs exhibited a targeting effect toward CSCs both in vitro and in vivo. These findings have important implications for the rational design of drug delivery systems that target CSCs with high efficacy.

An alginate-based platform for cancer stem cell research.

UNLABELLED: As the primary determinants of the clinical behaviors of human cancers, the discovery of cancer stem cells (CSCs) represents an ideal target for novel anti-cancer therapies (Kievit et al., 2014). Notably, CSCs are difficult to propagate in vitro, which severely restricts the study of CSC biology and the development of therapeutic agents. Emerging evidence indicates that CSCs rely on a niche that controls their differentiation and proliferation, as is the case with normal stem cells (NSCs). Replicating the in vivo CSC microenvironment in vitro using three-dimensional (3D) porous scaffolds can provide means to effectively generate CSCs, thus enabling the discovery of CSC biology. This paper presents our study on a novel alginate-based platform for mimicking the CSC niche to promote CSC proliferation and enrichment. In this study, we used a versatile mouse 4T1 breast cancer model to independently evaluate the matrix parameters of a CSC niche - including the material's mechanical properties, cytokine immobilization, and the composition of the extracellular matrix's (ECM's) molecular impact - on CSC proliferation and enrichment. On this basis, the optimal stiffness and concentration of hyaluronic acid (HA), as well as epidermal growth factor and basic fibroblast growth factor immobilization, were identified to establish the platform for mimicking the 4T1 breast CSCs (4T1 CSCs) niche. The 4T1 CSCs obtained from the platform show increased expression of the genes involved in breast CSC and NSC, as compared to general 2D or 3D culture, and 4T1 CSCs were also demonstrated to have the ability to quickly form a subcutaneous tumor in homologous Balb/c mice in vivo. In addition, the platform can be adjusted according to different parameters for CSC screening. Our results indicate that our platform offers a simple and efficient means to isolate and enrich CSCs in vitro, which can help researchers better understand CSC biology and thus develop more effective therapeutic agents to treat cancer. STATEMENT OF SIGNIFICANCE: As the primary determinants of the clinical behaviors of human cancers, the discovery of cancer stem cells (CSCs) represents an ideal target for novel anti-cancer therapies. However, CSCs are difficult to propagate in vitro, which severely restricts the study of CSC biology and the development of therapeutic agents. Emerging evidence indicates that CSCs rely on a niche that controls their differentiation and proliferation, as is the case with normal stem cells (NSCs). Replicating the in vivo CSC microenvironment in vitro using three-dimensional (3D) porous scaffolds can provide means to effectively generate CSCs, thus enabling the discovery of CSC biology. In our study, a novel alginate-based platform were developed for mimicking the CSC niche to promote CSC proliferation and enrichment.

Electrical impedance spectroscopy - a potential method for the study and monitoring of a bone critical-size defect healing process treated with bone tissue engineering and regenerative medicine approaches.

The development of strategies of bone tissue engineering and regenerative medicine has been drawing considerable attention to treat bone critical-size defects (CSDs). Notably, new strategies and/or treatment approaches always require appropriate tools to track the healing process so as to evaluate their success. In this paper, we present the development of a novel approach for the non-invasive, yet real-time, monitoring and assessment of bone CSDs treated with biomaterials and biomedical approaches. For this, we employed the technique of electrical impedance spectroscopy (EIS) to quantitatively monitor and assess the changes in electrical impedance, and thus the regeneration process. In our in vitro tests, we examined the biochemical changes of the fracture area and investigated the influence of collagen and hydroxyapatite on the changes in electrical impedance by EIS, thus inferring the changes in bone regeneration and structure. Based on this success, we further demonstrated, in real time, the process of regeneration of the traumatic area in an in vivo rabbit model. Our electrical-impedance data of the experiment groups, i.e., the ones treated with natural coral and bone morphogenetic protein-2 (BMP-2), revealed that each group has its unique impedance graph characteristics, which are directly associated with the degree of regeneration. For comparison, we also employed radiography, gross anatomy, and histological analyses in examination. Our results illustrate that EIS holds considerable potential as a non-invasive tool for monitoring, in real time, the healing of bone CSDs by allowing for quantitatively characterizing the changes of both hydroxyapatite and collagen.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.