The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body.

Spatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of intero-exteroceptive information integration to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of the self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0°, 90°, and 270° relative to the upright orientation, and when the front view was presented rather than the back view. Reflecting the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC), suggesting that the activation reflects the involvement of an embodied simulation in ALJ. Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants' interoceptive sensitivity, as assessed through the heartbeat discrimination task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues to spatially transform the image of our self-body.

Changes in Resting-State Brain Activity After Cognitive Behavioral Therapy for Chronic Pain: A Magnetoencephalography Study.

Cognitive behavioral therapy (CBT) is believed to be an effective treatment for chronic pain due to its association with cognitive and emotional factors. Nevertheless, there is a paucity of magnetoencephalography (MEG) investigations elucidating its underlying mechanisms. This study investigated the neurophysiological effects of CBT employing MEG and analytical techniques. We administered resting-state MEG scans to 30 patients with chronic pain and 31 age-matched healthy controls. Patients engaged in a 12-session group CBT program. We conducted pretreatment (T1) and post-treatment (T2) MEG and clinical assessments. MEG data were examined within predefined regions of interest, guided by the authors' and others' prior magnetic resonance imaging studies. Initially, we selected regions displaying significant changes in power spectral density and multiscale entropy between patients at T1 and healthy controls. Then, we examined the changes within these regions after conducting CBT. Furthermore, we applied support vector machine analysis to MEG data to assess the potential for classifying treatment effects. We observed normalization of power in the gamma2 band (61-90 Hz) within the right inferior frontal gyrus (IFG) and multiscale entropy within the right dorsolateral prefrontal cortex (DLPFC) of patients with chronic pain after CBT. Notably, changes in pain intensity before and after CBT positively correlated with the alterations of multiscale entropy. Importantly, responders predicted by the support vector machine classifier had significantly higher treatment improvement rates than nonresponders. These findings underscore the pivotal role of the right IFG and DLPFC in ameliorating pain intensity through CBT. Further accumulation of evidence is essential for future applications. PERSPECTIVE: We conducted MEG scans on 30 patients with chronic pain before and after a CBT program, comparing results with 31 healthy individuals. There were CBT-related changes in the right IFG and DLPFC. These results highlight the importance of specific brain regions in pain reduction through CBT.

Insula-cortico-subcortical networks predict interoceptive awareness and stress resilience.

BACKGROUND: Interoception, the neural sensing of visceral signals, and interoceptive awareness (IA), the conscious perception of interoception, are crucial for life survival functions and mental health. Resilience, the capacity to overcome adversity, has been associated with reduced interoceptive disturbances. Here, we sought evidence for our Insula Modular Active Control (IMAC) model that suggest that the insula, a brain region specialized in the processing of interoceptive information, realizes IA and contributes to resilience and mental health via cortico-subcortical connections. METHODS: 64 healthy participants (32 females; ages 18-34 years) answered questionnaires that assess IA and resilience. Mental health was evaluated with the Beck Depression Inventory II that assesses depressive mood. Participants also underwent a 15 minute resting-state functional resonance imaging session. Pearson correlations and mediation analyses were used to investigate the relationship between IA and resilience and their contributions to depressive mood. We then performed insula seed-based functional connectivity analyzes to identify insula networks involved in IA, resilience and depressive mood. RESULTS: We first demonstrated that resilience mediates the relationship between IA and depressive mood. Second, shared and distinct intra-insula, insula-cortical and insula-subcortical networks were associated with IA, resilience and also predicted the degree of experienced depressive mood. Third, while resilience was associated with stronger insula-precuneus, insula-cerebellum and insula-prefrontal networks, IA was linked with stronger intra-insula, insula-striatum and insula-motor networks. CONCLUSIONS: Our findings help understand the roles of insula-cortico-subcortical networks in IA and resilience. These results also highlight the potential use of insula networks as biomarkers for depression prediction.

Effects of Thermal Boundary Resistance on Thermal Management of Gallium-Nitride-Based Semiconductor Devices: A Review.

Wide-bandgap gallium nitride (GaN)-based semiconductors offer significant advantages over traditional Si-based semiconductors in terms of high-power and high-frequency operations. As it has superior properties, such as high operating temperatures, high-frequency operation, high breakdown electric field, and enhanced radiation resistance, GaN is applied in various fields, such as power electronic devices, renewable energy systems, light-emitting diodes, and radio frequency (RF) electronic devices. For example, GaN-based high-electron-mobility transistors (HEMTs) are used widely in various applications, such as 5G cellular networks, satellite communication, and radar systems. When a current flows through the transistor channels during operation, the self-heating effect (SHE) deriving from joule heat generation causes a significant increase in the temperature. Increases in the channel temperature reduce the carrier mobility and cause a shift in the threshold voltage, resulting in significant performance degradation. Moreover, temperature increases cause substantial lifetime reductions. Accordingly, GaN-based HEMTs are operated at a low power, although they have demonstrated high RF output power potential. The SHE is expected to be even more important in future advanced technology designs, such as gate-all-around field-effect transistor (GAAFET) and three-dimensional (3D) IC architectures. Materials with high thermal conductivities, such as silicon carbide (SiC) and diamond, are good candidates as substrates for heat dissipation in GaN-based semiconductors. However, the thermal boundary resistance (TBR) of the GaN/substrate interface is a bottleneck for heat dissipation. This bottleneck should be reduced optimally to enable full employment of the high thermal conductivity of the substrates. Here, we comprehensively review the experimental and simulation studies that report TBRs in GaN-on-SiC and GaN-on-diamond devices. The effects of the growth methods, growth conditions, integration methods, and interlayer structures on the TBR are summarized. This study provides guidelines for decreasing the TBR for thermal management in the design and implementation of GaN-based semiconductor devices.

Thermal treatment of water-soluble particles formed by compounds composed of carbon nanobelts and C60 molecules.

It was previously shown that spherical particles are self-assembled by compounds composed of C60-(6,6)CNB-C60, where CNB stands for "carbon nanobelt", by mixing two individual solutions of C60 and (6,6)CNB molecules dissolved in 1,2-dichlorobenzene at room temperature. The particles are monodisperse in water thanks to their high absolute value of the zeta potential in water. In this report, we investigate the effect of thermal treatment of the particles on some changes in the physical properties and structures. We find that the particles become electrically conductive after thermal treatment at 600 °C for 1 h. We suppose that the change in the electrical characteristics might have been caused by the structural change of (6,6)CNBs into opened-up ribbons composed of fused benzene rings, which construct networks supported by C60 molecules in the particles, judging by the change in the absorption and mass spectra of the particles after thermal treatment and analysis of a possible change in the structure of C60-(6,6)CNB-C60 based on quantum chemical calculations employing the PM6 method, with which it is known that nanostructures such as carbon nanotubes (CNTs) and (6,6)CNBs can be correctly estimated.

Insula neuroanatomical networks predict interoceptive awareness.

Interoceptive awareness (IA), the subjective and conscious perception of visceral and physiological signals from the body, has been associated with functions of cortical and subcortical neural systems involved in emotion control, mood and anxiety disorders. We recently hypothesized that IA and its contributions to mental health are realized by a brain interoception network (BIN) linking brain regions that receive ascending interoceptive information from the brainstem, such as the amygdala, insula and anterior cingulate cortex (ACC). However, little evidence exists to support this hypothesis. In order to test this hypothesis, we used a publicly available dataset that contained both anatomical neuroimaging data and an objective measure of IA assessed with a heartbeat detection task. Whole-brain Voxel-Based Morphometry (VBM) was used to investigate the association of IA with gray matter volume (GMV) and the structural covariance network (SCN) of the amygdala, insula and ACC. The relationship between IA and mental health was investigated with questionnaires that assessed depressive symptoms and anxiety. We found a positive correlation between IA and state anxiety, but not with depressive symptoms. In the VBM analysis, only the GMV of the left anterior insula showed a positive association with IA. A similar association was observed between the parcellated GMV of the left dorsal agranular insula, located in the anterior insula, and IA. The SCN linking the right dorsal agranular insula with the left dorsal agranular insula and left hyper-granular insula were positively correlated with IA. No association between GMV or SCN and depressive symptoms or anxiety were observed. These findings revealed a previously unknown association between IA, insula volume and intra-insula SCNs. These results may support development of non-invasive neuroimaging interventions, e.g., neurofeedback, seeking to improve IA and to prevent development of mental health problems, such anxiety disorders.

Direct Cardiac Epigenetic Reprogramming through Codelivery of 5'Azacytidine and miR-133a Nanoformulation.

Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintaining cellular identities. For instance, DNA methylation controls cell differentiation in adults, establishing that epigenetic factors are crucial for sustaining altered gene expression patterns with subsequent rounds of cell division. This study attempts to demonstrate that 5'AZA and miR-133a encapsulated in PLGA-PEI nanocarriers induce direct epigenetic reprogramming of cardiac fibroblasts to cardiomyocyte-like cells. The results present a cardiomyocyte-like phenotype following seven days of the co-delivery of 5'AZA and miR-133a nanoformulation into human cardiac fibroblasts. Further evaluation of the global DNA methylation showed a decreased global 5-methylcytosine (5-medCyd) levels in the 5'AZA and 5'AZA/miR-133a treatment group compared to the untreated group and cells with void nanocarriers. These results suggest that the co-delivery of 5'AZA and miR-133a nanoformulation can induce the direct reprogramming of cardiac fibroblasts to cardiomyocyte-like cells in-vitro, in addition to demonstrating the influence of miR-133a and 5'AZA as epigenetic regulators in dictating cell fate.

Room temperature synthesis of water-soluble spherical particles of a uniform diameter composed of carbon nanobelts and C60 molecules.

A carbon nanobelt (CNB) is a loop of fused benzene rings and a C60 molecule is a football shaped fullerene composed of 60 carbon atoms. In this study, we synthesize uniform spherical particles composed of (6,6)CNBs and C60 molecules in 1,2-dichlorobenzene at room temperature via bottom-up self-assembly, setting the molar concentrations of (6,6)CNBs and C60 molecules at appropriate values, and find that the particles are monodisperse even in water. The present room temperature synthetic methodology may well be applied to the creation of nano/micro structures/materials using basic carbon nano units such as cycloparaphenylene (CPP, carbon nanorings) and fullerenes; e.g., C60, C70 and C59N.

Fundidesulfovibrio magnetotacticus sp. nov., a sulphate-reducing magnetotactic bacterium, isolated from sediments and freshwater of a pond.

A sulphate-reducing magnetotactic bacterium, designated strain FSS-1T, was isolated from sediments and freshwater of Suwa Pond located in Hidaka, Saitama, Japan. Strain FSS-1T was a motile, Gram-negative and curved rod-shaped bacterium that synthesizes bullet-shaped magnetite (Fe3O4) nanoparticles in each cell. Strain FSS-1T was able to grow in the range of pH 6.5-8.0 (optimum, pH 7.0), 22-34 °C (optimum, 28 °C) and with 0-8.0 g l-1 NaCl (optimum, 0-2.0 g l-1 NaCl). Strain FSS-1T grew well in the presence of 50 µM ferric quinate as an iron source. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The major menaquinone was MK-7 (H2). Strain FSS-1T contained desulfoviridin, cytochrome c 3 and catalase, but did not contain oxidase. Strain FSS-1T used fumarate, lactate, pyruvate, malate, formate/acetate, succinate, tartrate, ethanol, 1-propanol, peptone, soytone and yeast extract as electron donors, while the strain used sulphate, thiosulphate and fumarate as electron acceptors. Fumarate was fermented in the absence of electron acceptors. Analysis of the 16S rRNA gene sequence showed that strain FSS-1T is a member of the genus Fundidesulfovibrio. The gene sequence showed 96.7, 95.0, 92.0, 91.2 and 91.4% similarities to the most closely related members of the genera Fundidesulfovibrio putealis B7-43T, Fundidesulfovibrio butyratiphilus BSYT, Desulfolutivibrio sulfoxidireducens DSM 107105T, Desulfolutivibrio sulfodismutans ThAc01T and Solidesulfovibrio magneticus RS-1T, respectively. The DNA G+C content of strain FSS-1T was 67.5 mol%. The average nucleotide identity value between strain FSS-1T and F. putealis B7-43T was 80.7 %. Therefore, strain FSS-1T represents a novel species within the genus Fundidesulfovibrio, for which the name Fundidesulfovibrio magnetotacticus sp. nov. is proposed (=JCM 32405T=DSM 110007T).

Albumin Stabilized Fe@C Core-Shell Nanoparticles as Candidates for Magnetic Hyperthermia Therapy.

Carbon-encapsulated iron nanoparticles (Fe@C) with a mean diameter of 15 nm have been synthesized using evaporation-condensation flow-levitation method by the direct iron-carbon gas-phase reaction at high temperatures. Further, Fe@C were stabilized with bovine serum albumin (BSA) coating, and their electromagnetic properties were evaluated to test their performance in magnetic hyperthermia therapy (MHT) through a specific absorption rate (SAR). Heat generation was observed at different Fe@C concentrations (1, 2.5, and 5 mg/mL) when applied 331 kHz and 60 kA/m of an alternating magnetic field, resulting in SAR values of 437.64, 129.36, and 50.4 W/g for each concentration, respectively. Having such high SAR values at low concentrations, obtained material is ideal for use in MHT.

Interoceptive accuracy is related to the psychological mechanisms of the burning mouth syndrome: a cross-sectional study.

BACKGROUND: Different perspectives are needed to understand the pathophysiology of burning mouth syndrome (BMS), including physiological and psychological standpoints. The significance of interoception in chronic pain has been suggested. However, few studies have investigated this relationship in BMS. Therefore, we examined the role of interoception in BMS. METHODS: This is a cross-sectional study. BMS patients (N = 64) participated in the study. We used interoceptive accuracy (IAc) based on the heartbeat counting task. Then, participants were divided into high and low IAc groups, and their scores on clinical assessment including pain and psychological evaluation were compared. RESULTS: The Visual Analogue Scale scores indicating pain in low IAc patients, but not high IAc patients, were positively correlated with the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-State (STAI-S) Scores. CONCLUSIONS: Interoception might play a role in the pathophysiology of BMS.

Chain Formation during Hydrogen Loss and Reconstruction in Carbon Nanobelts.

Using laser-induced vaporisation to evaporate and ionise a source of curved polyaromatic hydrocarbons (carbon nanobelts), we show collision impacts between species cause mass loss and the resultant ions are catalogued via mass-spectrometry. These data are interpreted via a series of "in-silico"-simulated systematic hydrogen-loss studies using density functional theory modelling, sequentially removing hydrogen atoms using thermodynamic stability as a selection for subsequent dehydrogenation. Initial hydrogen loss results in the formation of carbyne chains and pentagon-chains while the nanobelt rings are maintained, giving rise to new circular strained dehydrobenzoannulene species. The chains subsequently break, releasing CH and C2. Alternative routes towards the formation of closed-cages (fullerenes) are identified but shown to be less stable than chain formation, and are not observed experimentally. The results provide important information on collision degradation routes of curved molecular carbon species, and notably serve as a useful guide to high-energy impact conditions observed in some astrochemical environments.

Biological Synthesis of Bioactive Gold Nanoparticles from Inonotus obliquus for Dual Chemo-Photothermal Effects against Human Brain Cancer Cells.

The possibility for an ecologically friendly and simple production of gold nanoparticles (AuNPs) with Chaga mushroom (Inonotus obliquus) (Ch-AuNPs) is presented in this study. Chaga extract's reducing potential was evaluated at varied concentrations and temperatures. The nanoparticles synthesized were all under 20 nm in size, as measured by TEM, which is a commendable result for a spontaneous synthesis method utilizing a biological source. The Ch-AuNPs showed anti-cancer chemotherapeutic effects on human brain cancer cells which is attributed to the biofunctionalization of the AuNPs with Chaga bioactive components during the synthesis process. Further, the photothermal ablation capability of the as-prepared gold nanoparticles on human brain cancer cells was investigated. It was found that the NIR-laser induced thermal ablation of cancer cells was effective in eliminating over 80% of the cells. This research projects the Ch-AuNPs as promising, dual modal (chemo-photothermal) therapeutic candidates for anti-cancer applications.

Scaffold mediated delivery of dual miRNAs to transdifferentiate cardiac fibroblasts.

The standard scaffold-mediated delivery of drugs/biomolecules has been successful due to the unique attributes of scaffolds, specifically the electrospun polymeric scaffolds that mimic ECM are well suited for advanced regenerative applications. Cardiac tissue engineering includes the interpretation of cellular and molecular mechanisms concerning heart regeneration and identifying an efficient reprogramming strategy to overcome the limitation of delivery systems and enhance the reprogramming efficiency. This study is a step towards developing a functional scaffold through a parallel interpretation of electrospun PLLA scaffolds with two distinct topologies to achieve sustained delivery of two muscle-specific microRNAs (miR-1 and miR-133a) to directly reprogram the adult human cardiac fibroblasts into cardiomyocyte-like cells. Polyethyleneimine was used to form stable PEI-miRNA complexes through electrostatic interactions. These complexes were immobilized on the electrospun smooth and porous scaffolds, where a loading efficiency of ~96% for the fibronectin modified and ~38% for unmodified surfaces was observed, regardless of their surface topology. The in-vitro release experiment exhibited a biphasic release pattern of PEI-miRNA polyplexes from the scaffolds. These dual miRNA scaffold systems proved to be an excellent formulation since their combinatorial effect involving the topographic cues of electrospun fibers, and dual miRNAs helped control the cardiac fibroblast cell fate precisely.

Isolation and cultivation of a novel sulfate-reducing magnetotactic bacterium belonging to the genus Desulfovibrio.

Magnetotactic bacteria (MTB) synthesize magnetosomes composed of membrane-enveloped magnetite (Fe3O4) and/or greigite (Fe3S4) nanoparticles in the cells. It is known that the magnetotactic Deltaproteobacteria are ubiquitous and inhabit worldwide in the sediments of freshwater and marine environments. Mostly known MTB belonging to the Deltaproteobacteria are dissimilatory sulfate-reducing bacteria that biomineralize bullet-shaped magnetite nanoparticles, but only a few axenic cultures have been obtained so far. Here, we report the isolation, cultivation and characterization of a dissimilatory sulfate-reducing magnetotactic bacterium, which we designate "strain FSS-1". We found that the strain FSS-1 is a strict anaerobe and uses casamino acids as electron donors and sulfate as an electron acceptor to reduce sulfate to hydrogen sulfide. The strain FSS-1 produced bullet-shaped magnetite nanoparticles in the cells and responded to external magnetic fields. On the basis of 16S rRNA gene sequence analysis, the strain FSS-1 is a member of the genus Desulfovibrio, showing a 96.7% sequence similarity to Desulfovibrio putealis strain B7-43T. Futhermore, the magnetosome gene cluster of strain FSS-1 was different from that of Desulfovibrio magneticus strain RS-1. Thus, the strain FSS-1 is considered to be a novel sulfate-reducing magnetotactic bacterium belonging to the genus Desulfovibrio.

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy.

Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is similar to its predecessors such as the ansamycin class of molecules. To our knowledge, nanoformulations for luminespib remain unexplored for their anticancer potential. In the present study, we developed aqueous dispensable BSA NPs for controlled delivery of luminespib. The luminespib-loaded BSA NPs were characterized by SEM, TEM, FTIR, XPS, UV-visible spectroscopy and fluorescence spectroscopy. The results suggest that luminespib interacts by non-covalent reversible interactions with BSA to form drug-loaded BSA NPs (DNPs). Our in vitro evaluations suggest that DNP-based aqueous nanoformulations can be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy.

Nano delivery of natural substances as prospective autophagy modulators in glioblastoma.

Glioblastoma is the most destructive type of malignant brain tumor in humans due to cancer relapse. Latest studies have indicated that cancer cells are more reliant on autophagy for survival than non-cancer cells. Autophagy is entitled as programmed cell death type II and studies imply that it is a comeback of cancer cells to innumerable anti-cancer therapies. To diminish the adverse consequences of chemotherapeutics, numerous herbs of natural origin have been retained in cancer treatments. Additionally, autophagy induction occurs via their tumor suppressive actions that could cause cell senescence and increase apoptosis-independent cell death. However, most of the drugs have poor solubility and thus nano drug delivery systems possess excessive potential to improve the aqueous solubility and bioavailability of encapsulated drugs. There is a pronounced need for more therapies for glioblastoma treatment and hereby, the fundamental mechanisms of natural autophagy modulators in glioblastoma are prudently reviewed in this article.

Ultrafast synthesis of carbon quantum dots from fenugreek seeds using microwave plasma enhanced decomposition: application of C-QDs to grow fluorescent protein crystals.

Herein, we present the rapid synthesis of mono-dispersed carbon quantum dots (C-QDs) via a single-step microwave plasma-enhanced decomposition (MPED) process. Highly-crystalline C-QDs were synthesized in a matter of 5 min using the fenugreek seeds as a sustainable carbon source. It is the first report, to the best of our knowledge, where C-QDs were synthesized using MPED via natural carbon precursor. Synthesis of C-QDs requires no external temperature other than hydrogen (H2) plasma. Plasma containing the high-energy electrons and activated hydrogen ions predominantly provide the required energy directly into the reaction volume, thus maximizing the atom economy. C-QDs shows excellent Photoluminescence (PL) activity along with the dual-mode of excitation-dependent PL emission (blue and redshift). We investigate the reason behind the dual-mode of excitation-dependent PL. To prove the efficacy of the MPED process, C-QDs were also derived from fenugreek seeds using the traditional synthesis process, highlighting their respective size-distribution, crystallinity, quantum yield, and PL. Notably, C-QDs synthesis via MPED was 97.2% faster than the traditional thermal decomposition process. To the best of our knowledge, the present methodology to synthesize C-QDs via natural source employing MPED is three times faster and far more energy-efficient than reported so far. Additionally, the application of C-QDs to produce the florescent lysozyme protein crystals "hybrid bio-nano crystals" is also discussed. Such a guest-host strategy can be exploited to develop diverse and complex "bio-nano systems". The florescent lysozyme protein crystals could provide a platform for the development of novel next-generation polychrome luminescent crystals.

Direct Cardiac Reprogramming with Engineered miRNA Scaffolds.

Ischemic heart disease is a predominant cause of death worldwide. The loss or death of cardiomyocytes due to restricted blood flow often results in a cardiac injury. Myofibroblasts replace these injured cardiomyocytes to preserve structural integrity. However, the depleted cardiomyocytes lead to cardiac dysfunction such as pathological cardiac dilation, reduced cardiac contraction, and fibrosis. Repair and regeneration of myocardium are the best possible therapy for end-stage heart failure patients because the current cardiomyocytes restoration therapies are limited to heart transplantation only. The emergence of interests to directly reprogram a mammalian heart with minimal regenerative capacity holds a promising future in the field of cardiovascular regenerative medicine. Repair and regeneration become the two crucial factors in the field of cardiovascular regenerative medicine since heart muscles have no substitutes, like heart valves or blood vessels. Cardiac regeneration includes strategies to reprogram with diverse factors like small molecules, genetic and epigenetic regulators. However, there are some constraints like low efficacy, immunogenic problems, and unsafe delivery systems that pose a daunting challenge in human trial translations. Hence, there is a need for a holistic nanoscale approach in regulating cell fate effectively and efficiently with a safer delivery and a suitable microenvironment that mimics the extracellular matrix. In this review, we have discussed the current state-of-the-art techniques, challenges in direct reprogramming of fibroblasts to cardiac muscle, and prospects of biomaterials in miRNA delivery and cardiac regeneration predominantly during the past decade (2008-2019).

ECM Mimetic Electrospun Porous Poly (L-lactic acid) (PLLA) Scaffolds as Potential Substrates for Cardiac Tissue Engineering.

Cardiac tissue engineering (CTE) aims to generate potential scaffolds to mimic extracellular matrix (ECM) for recreating the injured myocardium. Highly porous scaffolds with properties that aid cell adhesion, migration and proliferation are critical in CTE. In this study, electrospun porous poly (l-lactic acid) (PLLA) porous scaffolds were fabricated and modified with different ECM derived proteins such as collagen, gelatin, fibronectin and poly-L-lysine. Subsequently, adult human cardiac fibroblasts (AHCF) were cultured on the protein modified and unmodified fibers to study the cell behavior and guidance. Further, the cytotoxicity and reactive oxygen species (ROS) assessments of the respective fibers were performed to determine their biocompatibility. Excellent cell adhesion and proliferation of the cardiac fibroblasts was observed on the PLLA porous fibers regardless of the surface modifications. The metabolic rate of cells was on par with the conventional cell culture ware while the proliferation rate surpassed the latter by nearly two-folds. Proteome profiling revealed that apart from being an anchorage platform for cells, the surface topography has modulated significant expression of the cellular proteome with many crucial proteins responsible for cardiac fibroblast growth and proliferation.