SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA ß-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

Minimally Invasive Surgery for Adolescent Idiopathic Scoliosis: A Systematic Review.

Background: Minimally invasive surgical (MIS) techniques have gained popularity as a safe and effective alternative to open surgery for degenerative, traumatic, and metastatic spinal pathologies. In adolescent idiopathic scoliosis, MIS techniques comprise anterior thoracoscopic surgery (ATS), posterior minimally invasive surgery (PMIS), and vertebral body tethering (VBT). In the current systematic review, the authors collected and analyzed data from the available literature on MIS techniques in AIS. Methods: The articles were shortlisted after a thorough electronic and manual database search through PubMed, EMBASE, and Google Scholar. Results: The authors included 43 studies for the review; 14 described the outcomes with ATS, 13 with PMIS, and 16 with VBT. Conclusions: While the efficacy of the ATS approach is well-established in terms of comparable coronal and sagittal correction to posterior spinal fusion, the current use of ATS for instrumented fusion has become less popular due to a steep learning curve, high pulmonary and vascular complication rates, implant failures, and increased non-union rates. PMIS is an effective alternative to the standard open posterior spinal fusion, with a steep learning curve and longer surgical time being potential disadvantages. The current evidence, albeit limited, suggests that VBT is an attractive procedure that merits consideration in terms of radiological correction and clinical outcomes, but it has a high complication and re-operation rate, while the most appropriate indications and long-term outcomes of this technique remain unclear.

Cryosphere: a frozen home of microbes and a potential source for drug discovery.

The world is concerned about the emergence of pathogens and the occurrence and spread of antibiotic resistance among pathogens. Drug development requires time to combat these issues. Consequently, drug development from natural sources is unavoidable. Cryosphere represents a gigantic source of microbes that could be the bioprospecting source of natural products with unique scaffolds as molecules or drug templates. This review focuses on the novel source of drug discovery and cryospheric environments as a potential source for microbial metabolites having potential medicinal applications. Furthermore, the problems encountered in discovering metabolites from cold-adapted microbes and their resolutions are discussed. By adopting modern practical approaches, the discovery of bioactive compounds might fulfill the demand for new drug development.

Congenital Afibrinogenemia With Facial Haematoma.

Congenital afibrinogenemia is a rare inherited blood disorder characterized by a deficiency of fibrinogen, leading to abnormal blood clotting. It is caused by mutations in fibrinogen genes and results in a propensity for bleeding. We present the case of a one-year-old male child with congenital afibrinogenemia who developed a left-sided facial haematoma following a fall from a walker. The child had a history of active bleeding during cannulation and had not undergone circumcision due to the risk of bleeding. This case highlights the need for timely diagnosis and appropriate management of rare bleeding disorders such as congenital afibrinogenemia. Collaboration between different specialties, including haematology and genetic counseling, is crucial for comprehensive care. The rarity of the condition underscores the importance of raising awareness among healthcare professionals. Genetic counseling and family studies are essential for assessing genetic implications and guiding decision-making. Further advancements in diagnostic tests and replacement therapy are needed to improve the management of patients with afibrinogenemia, particularly in regions with a high prevalence of consanguineous marriages.

Classic central nervous system Hodgkin lymphoma masquerading as left sphenoid wing meningioma- A case report.

INTRODUCTION AND IMPORTANCE: Classic Hodgkin Lymphoma with an incidence of 2-3 cases per 100,000 population affects the Central Nervous System in 0.02 % of cases (Gerstner et al., 2008; Brice et al., 2021; Morawa et al., 2007). CNS lymphoma, contributing to 0.22 % of Central Nervous System tumors, is the uncommon extra-nodal manifestation of Hodgkin's Disease (Brice et al., 2021; Henkenberens et al., 2014). It affects the nervous system secondary to systemic lymphoma or the relapse of the disease (Gerstner et al., 2008). Only 17 cases of CNS lymphoma are reported which were limited to the CNS at the time of diagnosis (Paul et al., 2017). Only two cases of Dural-Based Hodgkin Lymphoma were reported in the literature (Paul et al., 2017). CASE PRESENTATION: We are reporting the third case of dural-attached extra-axial secondary CNS Hodgkin Lymphoma in a 33 years old female, which appeared and was operated as Left Sphenoid Wing Meningioma. CLINICAL DISCUSSION: Only 17 cases of CNS lymphoma are reported which were limited to the CNS at the time of diagnosis (Paul et al., 2017). Only two cases of Dural-Based Hodgkin Lymphoma were reported in the literature (Paul et al., 2017). Our case consists the third case of dural attached Classic CNS Hodgkin lymphoma and the first case of Classic CNS Hodgkin Lymphoma locating in the Sphenoid Wing. CONCLUSION: It is important to differentiate CNS Hodgkin Lymphoma from other types of brain tumors especially when it resides in an unusual location because the treatment of CNS Hodgkin Lymphoma is mainly combined chemo-radiotherapy than surgical intervention.

Ferroptosis and Triple-Negative Breast Cancer: A Systematic Overview of Prognostic Insights and Therapeutic Potential.

In the realm of oncology, the prognosis and treatment of triple-negative breast cancer (TNBC) have long been challenges for researchers and clinicians. Characterized by its aggressive nature and limited therapeutic options, TNBC demands innovative approaches to understanding its underlying mechanisms and improving patient outcomes. One such avenue of exploration that has emerged in recent years is the study of ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation. Ferroptosis has garnered increasing attention due to its potential relevance in the context of TNBC. This systematic review aims to shed light on the intricate interplay between ferroptosis and the prognosis of TNBC. The article delves into a comprehensive examination of the existing literature to provide a holistic understanding of the subject. By investigating ferroptosis as both an intervention and a prognostic factor in TNBC, this article seeks to unravel its potential as a therapeutic target and prognostic marker. The emerging evidence and heterogeneity of ferroptosis in TNBC underscore the need for a systematic approach to assess its impact on patient outcomes. This review will serve as a valuable resource for researchers, clinicians, and healthcare professionals striving to enhance our knowledge of TNBC and explore novel avenues for prognosis and treatment.

Revisiting Dimorphs of 4-n-octyloxybenzoic Acid: Contrasting Mechanical Property and Surface Wettability.

4-n-octyloxy benzoic acid is known to exhibit liquid crystalline properties, and under normal pressure and temperature conditions, it exists as at least two crystalline polymorphs. We revisited the system and discovered that single crystals of one of the polymorphs display plastic deformation, whereas the other is brittle. n-octyl chains are arranged in an end-to-end fashion, forming slip planes in the plastically deformable polymorph, whereas they are interdigitated in the crystal structure of the brittle polymorph. Due to the difference in the arrangement of the -COOH group and alkyl chains, the major faces of the crystals of both polymorphs possess significant differences in the wettability towards moisture.

Direct differentiation of rat skin fibroblasts into cardiomyocytes.

Myocardial infarction (MI) is one of the major cardiovascular diseases caused by diminished supply of nutrients and oxygen to the heart due to obstruction of the coronary artery. Different treatment options are available for cardiac diseases, however, they do not completely repair the damage. Therefore, reprogramming terminally differentiated fibroblasts using transcription factors is a promising strategy to differentiate them into cardiac like cells in vitro and to increase functional cardiomyocytes and reduce fibrotic scar in vivo. In this study, skin fibroblasts were selected for reprogramming because they serve as a convenient source for the autologous cell therapy. Fibroblasts were isolated from skin of rat pups, propagated, and directly reprogrammed towards cardiac lineage. For reprogramming, two different approaches were adopted, i.e., cells were transfected with: (1) combination of cardiac transcription factors; GATA4, MEF2c, Nkx2.5 (GMN), and (2) combination of cardiac transcription factors; GATA4, MEF2c, Nkx2.5, and iPSC factors; Oct4, Klf4, Sox2 and cMyc (GMNO). After 72 h of transfection, cells were analyzed for the expression of cardiac markers at the mRNA and protein levels. For in vivo study, rat MI models were developed by ligating the left anterior descending coronary artery and the reprogrammed cells were transplanted in the infarcted heart. qPCR results showed that the reprogrammed cells exhibited significant upregulation of cardiac genes. Immunocytochemistry analysis further confirmed cardiomyogenic differentiation of the reprogrammed cells. For the assessment of cardiac function, animals were analyzed via echocardiography after 2 and 4 weeks of cell transplantation. Echocardiographic results showed that the hearts transplanted with the reprogrammed cells improved ejection fraction, fractional shortening, left ventricular internal systolic and diastolic dimensions, and end systolic and diastolic volumes. After 4 weeks of cell transplantation, heart tissues were harvested and processed for histology. The histological analysis showed that the reprogrammed cells improved wall thickness of left ventricle and reduced fibrosis significantly as compared to the control. It is concluded from the study that novel combination of cardiac transcription factors directly reprogrammed skin fibroblasts and differentiated them into cardiomyocytes. These differentiated cells showed cardiomyogenic characters in vitro, and reduced fibrosis and improved cardiac function in vivo. Furthermore, direct reprogramming of fibroblasts transfected with cardiac transcription factors showed better regeneration of the injured myocardium and improved cardiac function as compared to the indirect approach in which combination of cardiac and iPSC factors were used. The study after further optimization could be used as a better strategy for cell-based therapeutic approaches for cardiovascular diseases.

Mind Matters: Exploring the Intersection of Psychological Factors and Cognitive Abilities of University Students by Using ANN Model.

Purpose: While previous studies have suggested close association of psychological variables of students withtheir higher-order cognitive abilities, such studies have largely been lacking for third world countries like India, with their unique socio-economic-cultural set of challenges. We aimed to investigate the relationship between psychological variables (depression, anxiety and stress) and cognitive functions among Indian students, and to predict cognitive performance as a function of these variables. Patients and Methods: Four hundred and thirteen university students were systematically selected using purposive sampling. Widely used and validated offline questionnaires were used to assess their psychological and cognitive statuses. Correlational analyses were conducted to examine the associations between these variables. An Artificial Neural Network (ANN) model was applied to predict cognitive levels based on the scores of psychological variables. Results: Correlational analyses revealed negative correlations between emotional distress and cognitive functioning. Principal Component Analysis (PCA) reduced the dimensionality of the input data, effectively capturing the variance with fewer features. The feature weight analysis indicated a balanced contribution of each mental health symptom, with particular emphasis on one of the symptoms. The ANN model demonstrated moderate predictive performance, explaining a portion of the variance in cognitive levels based on the psychological variables. Conclusion: The study confirms significant associations between emotional statuses of university students with their cognitive abilities. Specifically, we provide evidence for the first time that in Indian students, self-reported higher levels of stress, anxiety, and depression are linked to lower performance in cognitive tests. The application of PCA and feature weight analysis provided deeper insights into the structure of the predictive model. Notably, use of the ANN model provided insights into predicting these cognitive domains as a function of the emotional attributes. Our results emphasize the importance of addressing mental health concerns and implementing interventions for the enhancement of cognitive functions in university students.

MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aß) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition.

Investigation of Photoluminescence and Optoelectronics Properties of Transition Metal-Doped ZnO Thin Films.

Thin films of zinc oxide (ZnO) doped with transition metals have recently gained significant attention due to their potential applications in a wide range of optoelectronic devices. This study focuses on ZnO thin films doped with the transition metals Co, Fe, and Zr, exploring various aspects of their structural, morphological, optical, electrical, and photoluminescence properties. The thin films were produced using RF and DC co-sputtering techniques. The X-ray diffraction (XRD) analysis revealed that all the doped ZnO thin films exhibited a stable wurtzite crystal structure, showcasing a higher structural stability compared to the undoped ZnO, while the atomic force microscopy (AFM) imaging highlighted a distinctive granular arrangement. Energy-dispersive X-ray spectroscopy was employed to confirm the presence of transition metals in the thin films, and Fourier-transform infrared spectroscopy (FTIR) was utilized to investigate the presence of chemical bonding. The optical characterizations indicated that doping induced changes in the optical properties of the thin films. Specifically, the doped ZnO thin film's bandgap experienced a significant reduction, decreasing from 3.34 to 3.30 eV. The photoluminescence (PL) analysis revealed distinguishable emission peaks within the optical spectrum, attributed to electronic transitions occurring between different bands or between a band and an impurity. Furthermore, the introduction of these transition metals resulted in decreased resistivity and increased conductivity, indicating their positive influence on the electrical conductivity of the thin films. This suggests potential applications in solar cells and light-emitting devices.

Norfloxacin derivatives as DNA gyrase and urease inhibitors: synthesis, biological evaluation and molecular docking.

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn's disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (1H NMR, Fourier transform IR, 13C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC50 of 0.15 ± 0.24 and 1.14 ± 0.11 µM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.

Investigating the biochemical association of gestational diabetes mellitus with dyslipidemia and hemoglobin.

Aims: To investigate the biochemical correlation of hemoglobin (Hb), dyslipidemia, and HbA1c with gestational diabetes mellitus (GDM). Background: GDM is a condition that develops during pregnancy and is characterized by high blood sugar levels. Biochemical parameters such as hemoglobin (Hb), dyslipidemia, and HbA1c have been implicated in the development of GDM. Understanding the correlation between these biochemical parameters and GDM can provide insights into the underlying mechanisms and potential diagnostic markers for the condition. Objective: The objective of this study was to evaluate the correlation of various biochemical parameters, including Hb, dyslipidemia, and HbA1c, in pregnant women with and without GDM. Method: A cross-sectional study design was used. Pregnant females attending a tertiary care hospital in Faisalabad between September 1st, 2021, and June 25th, 2022, were included in the study. The participants were divided into two groups: those with GDM (GDM group) and those without GDM (non-GDM group). Blood glucose, Hb, and lipid levels were compared between the two groups using statistical tests, including chi-square, independent sample t-test, and Pearson's correlation. Result: Out of the 500 participants, 261 were in the 2nd trimester and 239 in the 3rd trimester. Maternal age showed a significant difference between the GDM and non-GDM groups. The levels of Hb, TC, HDL, LDL, and HbA1c significantly differed (p < 0.05) between the two groups. TC (r = 0.397), TG (r = 0.290), and LDL (r = 0.509) showed a statistically significant and moderately positive correlation with GDM. HDL (r = -0.394) and Hb (r = -0.294) showed a moderate negative correlation with GDM. Conclusion: Increased levels of HbA1c, TC, and LDL, along with decreased levels of HDL and Hb, were identified as contributing factors to GDM. The levels of TC, TG, and LDL were positively correlated with GDM, while HDL and Hb were negatively correlated. The findings of this study suggest that monitoring and managing hemoglobin, dyslipidemia, and HbA1c levels during pregnancy may be important in identifying and potentially preventing or managing GDM. Further research is needed to explore the underlying mechanisms and potential interventions targeting these biochemical parameters in relation to GDM.

Identification of methylation-regulated genes modulating microglial phagocytosis in hyperhomocysteinemia-exacerbated Alzheimer's disease.

BACKGROUND: Hyperhomocysteinemia (HHcy) has been linked to development of Alzheimer's disease (AD) neuropathologically characterized by the accumulation of amyloid ß (Aß). Microglia (MG) play a crucial role in uptake of Aß fibrils, and its dysfunction worsens AD. However, the effect of HHcy on MG Aß phagocytosis remains unstudied. METHODS: We isolated MG from the cerebrum of HHcy mice with genetic cystathionine-ß-synthase deficiency (Cbs-/-) and performed bulk RNA-seq. We performed meta-analysis over transcriptomes of Cbs-/- mouse MG, human and mouse AD MG, MG Aß phagocytosis model, human AD methylome, and GWAS AD genes. RESULTS: HHcy and hypomethylation conditions were identified in Cbs-/- mice. Through Cbs-/- MG transcriptome analysis, 353 MG DEGs were identified. Phagosome formation and integrin signaling pathways were found suppressed in Cbs-/- MG. By analyzing MG transcriptomes from 4 AD patient and 7 mouse AD datasets, 409 human and 777 mouse AD MG DEGs were identified, of which 37 were found common in both species. Through further combinatory analysis with transcriptome from MG Aß phagocytosis model, we identified 130 functional-validated Aß phagocytic AD MG DEGs (20 in human AD, 110 in mouse AD), which reflected a compensatory activation of Aß phagocytosis. Interestingly, we identified 14 human Aß phagocytic AD MG DEGs which represented impaired MG Aß phagocytosis in human AD. Finally, through a cascade of meta-analysis of transcriptome of AD MG, functional phagocytosis, HHcy MG, and human AD brain methylome dataset, we identified 5 HHcy-suppressed phagocytic AD MG DEGs (Flt1, Calponin 3, Igf1, Cacna2d4, and Celsr) which were reported to regulate MG/MΦ migration and Aß phagocytosis. CONCLUSIONS: We established molecular signatures for a compensatory response of Aß phagocytosis activation in human and mouse AD MG and impaired Aß phagocytosis in human AD MG. Our discoveries suggested that hypomethylation may modulate HHcy-suppressed MG Aß phagocytosis in AD.

Morphological, Photoluminescence, and Electrical Measurements of Rare-Earth Metal-Doped Cadmium Sulfide Thin Films.

This work is aimed at investigating the viability of utilizing cadmium sulfide (CdS) as a buffer layer in CdTe solar cells by analyzing and assessing its optical, photoluminescence, morphological, and electrical properties. These films were fabricated using a thermal coating technique. Optical microscopy was used to observe the changes in morphology resulting from the doping of rare-earth metals such as samarium (Sm) and lanthanum (La) to CdS, while the granular-like structure of the sample was confirmed by scanning electron microscopy. The objective of incorporating Sm and La ions into CdS was to enhance photoconductivity and optimize the optical bandgap, aiming to create a viable charge transport material for photovoltaic devices with enhanced efficiency. Through that process, a noticeable decrease in transmission, from approximately 80 to 68% in the visible region, was observed. Additionally, the bandgap value was reduced from 2.43 to 2.27 eV. Furthermore, during the analysis of the photoluminescence spectra, it was observed that emission peaks occurred in the visible region. These emissions were attributed to electronic transitions that took place via band-to-band and band-to-impurity interactions. The electrical measurements showed an enhancement in conductivity due to the decrease in the bandgap. This notable consequence of the doped materials suggests their utilization in photovoltaic systems.

miR-182/183-Rasa1 axis induced macrophage polarization and redox regulation promotes repair after ischemic cardiac injury.

Few therapies have produced significant improvement in cardiac structure and function after ischemic cardiac injury (ICI). Our possible explanation is activation of local inflammatory responses negatively impact the cardiac repair process following ischemic injury. Factors that can alter immune response, including significantly altered cytokine levels in plasma and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI is a valid strategy for reducing infarct size and damage after myocardial injury. Our previous studies showed that cortical bone stem cells (CBSCs) possess reparative effects after ICI. In our current study, we have identified that the beneficial effects of CBSCs appear to be mediated by miRNA in their extracellular vesicles (CBSC-EV). Our studies showed that CBSC-EV treated animals demonstrated reduced scar size, attenuated structural remodeling, and improved cardiac function versus saline treated animals. These effects were linked to the alteration of immune response, with significantly altered cytokine levels in plasma, and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI. Our detailed in vitro studies demonstrated that CBSC-EV are enriched in miR-182/183 that mediates the pro-reparative polarization and metabolic reprogramming in macrophages, including enhanced OXPHOS rate and reduced ROS, via Ras p21 protein activator 1 (RASA1) axis under Lipopolysaccharides (LPS) stimulation. In summary, CBSC-EV deliver unique molecular cargoes, such as enriched miR-182/183, that modulate the immune response after ICI by regulating macrophage polarization and metabolic reprogramming to enhance repair.

The Uncertain Benefit from Implantable Cardioverter-Defibrillators in Nonischemic Cardiomyopathy: How to Guide Clinical Decision-Making?

Life-threatening dysrhythmias remain a significant cause of mortality in patients with nonischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillators (ICD) effectively reduce mortality in patients who have survived a life-threatening arrhythmic event. The evidence for survival benefit of primary prevention ICD for patients with high-risk NICM on guideline-directed medical therapy is not as robust, with efficacy questioned by recent studies. In this review, we summarize the data on the risk of life-threatening arrhythmias in NICM, the recommendations, and the evidence supporting the efficacy of primary prevention ICD, and highlight tools that may improve the identification of patients who could benefit from primary prevention ICD implantation.