Search Results (957)

Impaired wound healing is a major cause of morbidity among patients with diabetes. Human α1-antitrypsin (hAAT) promotes the resolution of injured tissues. In hyperglycemic conditions, circulating hAAT is likely to undergo glycation, yet it is unknown whether its reparative properties are preserved. We hypothesized that clinical-grade hAAT treatment, but not deliberately glycated hAAT (gly-hAAT), would promote wound repair under hyperglycemic conditions. Mice were rendered hyperglycemic, excisional wounding was performed, and wounds were treated with topical albumin or hAAT every three days. The wound area was assessed, and samples were collected for histology and gene expression analysis. Gly-hAAT was generated from clinical-grade hAAT, after which in vitro RAW 264.7 macrophage responses and re-epithelialization of A549 cells were assessed. Gap closure was further assessed using sera from a human cohort (prospective samples from 10 patients with poorly controlled diabetes at Soroka University Medical Center, Beer-Sheva, Israel, 2018). Group comparisons were performed using one-way ANOVA with Tukey’s post hoc test. hAAT accelerated in vivo wound closure and in vitro A549 cell gap closure, accompanied by an anti-inflammatory IL-1Ra/IL-1β gene expression profile. In contrast, gly-hAAT inhibited normoglycemic mouse wound closure, evoked an inflammatory response in macrophages, and interfered with A549 cell gap closure; concomitant hAAT treatment improved gap closure. Similarly, patient serum inhibited A549 gap closure, and concomitant hAAT treatment improved gap closure. Importantly, inferential statistical analysis was not performed on this outcome due to the small and heterogeneous human cohort. In conclusion, hAAT accelerated wound closure in hyperglycemic mice and in A549 cells, whereas gly-hAAT promoted inflammatory responses and impaired wound closure, a trend reversed by native hAAT. These findings support the concept that glycation undermines the beneficial functions of circulating hAAT and provides a mechanistic insight into the pathophysiology of diabetic wound healing. Further studies are warranted to evaluate clinical-grade hAAT as a potential therapeutic for hyperglycemia-associated impaired wound healing. Full article

Ovarian cancer (OC) remains one of the deadliest gynecological malignancies, largely due to late diagnosis and the emergence of resistance to platinum–based chemotherapy. Long non–coding RNAs (lncRNAs) have recently emerged as key regulators of tumor progression and therapeutic adaptation. In this study, we performed integrative transcriptomic profiling of patient–derived TCGA ovarian tumor samples and carboplatin–resistant A2780 (CBDCA–R–A2780) cells to identify lncRNAs whose dysregulation overlaps between a cell–line resistance model and patient tumors. Our analyses revealed extensive transcriptional remodeling across both datasets, with MNX1–AS1 consistently emerging as a strongly deregulated transcript. Differential expression analysis showed robust upregulation of MNX1–AS1 in resistant cells and tumor tissues, accompanied by correlations with epithelial–mesenchymal transition (EMT)–related transcription factors such as FOXA1 and SNAI2 and inverse associations with epithelial markers including CDH1. Computational predictions using RIblast identified specific MNX1–AS1 binding regions with candidate miRNAs and mRNAs, prioritizing EMT–related transcripts (e.g., SNAI2, FOXA1, ZEB1) with favorable hybridization energies for future validation. Additional prioritized interactors included genes linked to stress response (IER2, FOSB) and invasion (MMP11, MMP1). Because A2780 has been discussed as an endometrioid–like/non–serous ovarian cancer model, mechanistic inferences primarily apply to this in vitro context, while TCGA analyses provide associative support rather than mechanistic validation. Collectively, these findings highlight MNX1–AS1 as a candidate regulator associated with transcriptional reprogramming in OC and a promising prognostic biomarker warranting further functional testing. Full article

This study compared the wound-healing response and osteogenic gene expression profile of osteoblasts exposed to pediatric-equivalent concentrations of dexmedetomidine (DXMT) and propofol (POF). Human osteoblast-like SAOS-2 cells were assigned to control, low- and high-dose DXMT and POF groups based on pharmacokinetically derived free-drug levels. Scratch-wound closure was quantified over 24 h, and expression of osteogenesis- and cytoskeleton-related genes (RANKL, RUNX2, SP7, BMP2, VIM, VCL, OCN, ALP) was measured by SYBR Green quantitative Polymerase Chain Reaction (qPCR). Normality was assessed using the Shapiro–Wilk test, and group differences were analyzed with two-way ANOVA followed by Tukey’s multiple comparisons test (p < 0.05). All groups demonstrated complete scratch closure by 24 h, with no differences at 6 h. At 18 h, POF did not differ from the control, whereas DXMT significantly accelerated closure at both doses in a dose-dependent fashion. High-dose DXMT significantly increased VIM (3.95 ± 3.12, p = 0.0144) and BMP2 (2.28 ± 0.70, p = 0.0002) expression, while RUNX2, SP7, and RANKL remained comparable to controls. ALP (1.68 ± 0.40, p = 0.0005) and OCN (3.31 ± 0.35, p = 0.0108) were significantly elevated only in the high-dose DXMT group, whereas POF showed no significant effects. At clinically relevant concentrations, DXMT was associated with enhanced scratch closure and increased expression of selected osteogenesis- and cytoskeleton-related genes in SAOS-2 cells, whereas POF showed limited effects under the tested conditions. These findings suggest that DXMT may influence early in vitro cellular responses relevant to bone healing and should be further validated in functional differentiation models and in vivo studies. Full article

The human microbiome influences health and disease through diverse biochemical and functional outputs (e.g., enzymes, structural proteins, metabolites, and other cellular components) that affect nearly every aspect of human physiology. Metatranscriptomics (MT), an unbiased RNA sequencing approach, is a high-throughput and high-content method that quantifies both gut microbial taxonomy and active biochemical functions. Because microbial community composition and gene expression are dynamic, understanding temporal variation in the gut metatranscriptome across multiple time scales is essential. Here, we report the temporal dynamics of gut microbiome species and functions using a large cohort (n = 6157) with a clinically validated stool MT test. We quantified microbiome stability from hours to years and assessed taxonomic and functional resilience to major luminal perturbations, such as colonoscopy bowel preparation. Longitudinal analyses of samples collected within the same day, and across days, weeks, months, and years, revealed consistently high stability in both composition and gene expression within a single day and, importantly, across an approximate six-month period. Among individuals reporting stable diets and no antibiotic exposure, taxonomic and functional profiles remained stable for up to three years. Following colonoscopy preparation, our preliminary study of the microbiome demonstrated strong resilience, returning to its pre-procedure state within one week. Overall, these findings demonstrate that the gut microbiome is generally stable over a six-month time frame, with longer-term changes occurring gradually. These findings support the robustness of stool-based MT profiling for species-level and pathway-resolved functional analysis in longitudinal research and health applications. Full article

This study aims to elucidate the miRNA regulatory mechanisms during the developmental process of Kazakh horse testes at 1 and 3 years of age. Through miRNA sequencing and bioinformatics analysis of testicular tissues from 1-year-old and 3-year-old horses, a developmentally stage-specific miRNA expression profile was constructed. A total of 1640 miRNAs were identified, among which 437 (380 up-regulated and 57 down-regulated) exhibited significant differential expression between the two age groups, including eca-miR-16, eca-miR-17, eca-miR-103, and eca-miR-199a-5p. Functional enrichment analysis revealed that the target genes of these differentially expressed miRNAs were primarily involved in key processes such as oxidative stress response, hormone receptor signaling regulation, and cytoskeletal remodeling, suggesting that testicular maturation depends on a complex post-transcriptional regulatory network. Further KEGG analysis revealed significant enrichment of classic reproductive signaling pathways, including PI3K/AKT, Wnt/β-catenin, Hippo, and TGF-β, indicating their synergistic roles in spermatocyte proliferation/differentiation and testicular homeostasis establishment. Although limited by a small sample size, this study elucidates the molecular mechanisms underlying male reproductive maturation in Kazakh horses at the post-transcriptional regulatory network level, providing preliminary theoretical support and potential markers for evaluating stallion reproductive performance and molecular breeding. Full article

Background: Kölliker’s organ (KO) support cells undergo orderly, time-dependent degeneration that is essential for auditory development and is accompanied by precisely regulated autophagic activity; however, the molecular hierarchy linking autophagy to this remodeling remains obscure. This study aimed to elucidate the regulatory mechanisms connecting autophagic flux to lysosomal biogenesis and auditory function during cochlear development. Method: We established an Atg5^flox/flox; Sox2Cre+ mouse model with deletion of the autophagy gene Atg5 in cochlear-supporting cells. Auditory function was assessed via Auditory Brainstem Response (ABR) testing. Transcriptomic profiling of the neonatal basilar membrane was performed to screen for downstream targets. Mechanistic validation included spatiotemporal immunofluorescence mapping (E18–P30) and in vitro functional assays using siRNA-mediated knockdown and lysosomal tracking. Results: At 2 months of age, Atg5^flox/flox; Sox2Cre+ mice exhibited moderate-to-severe sensorineural hearing loss accompanied by significant outer hair cell loss. Bulk RNA-seq of the basilar membrane identified fork-head box A3 (Foxa3) as a significantly downregulated transcription factor within the lysosomal–autophagy network. Spatiotemporal immunolabelling from embryonic day 18 to postnatal day 30 revealed that FOXA3 expression becomes progressively restricted to KO cells during postnatal development, with ATG5 loss reducing FOXA3 protein levels by 62.4%. In vitro, deficiency of either Atg5 or Foxa3 in primary KO cells resulted in comparable reductions in LAMP1-positive puncta. Conclusions: These findings support a model wherein the ATG5-FOXA3 axis contributes to lysosomal biogenesis in developing KO cells, with implications for understanding mechanisms of congenital sensorineural hearing loss. Full article

Major depressive disorder (MDD) lacks reliable laboratory tests for diagnosis and treatment monitoring, underscoring the need for robust molecular readouts in blood. Beyond symptom-based classification, MDD can also be viewed as a condition involving impaired homeostatic regulation across stress-responsive, immune, metabolic, and neural systems. Consistent with this perspective, altered intron retention (IR) patterns have been observed in peripheral blood in depression-related and treatment-response contexts, supporting the translational relevance of this RNA-processing layer to mood disorders. A key observation underpinning this review is that IR can function as a reversible, intervention-responsive readout of physiological state. In a pre-symptomatic stress-like state in klotho mutant mice (a premature-aging model), widespread IR increases revert toward a healthy pattern upon treatment, suggesting that IR is embedded in a controllable homeostatic layer. Against the backdrop of limited cross-cohort transferability of differential gene expression (DGE) signatures, we propose that IR provides a mechanistically grounded biomarker layer because it reports regulated RNA processing states rather than context-fragile abundance endpoints. We operationalize IR as a post-transcriptional “throttle” on effective gene output, with increased IR/detained intron (DI) states acting as a reversible brake and decreased IR acting as an accelerator that increases translation-competent mRNA supply. Mechanistic exemplars across immune, metabolic, and neuronal systems (e.g., IFNG, OGT, MAT2A, neuronal activity-triggered intron excision, and intron detention-mediated stemness/differentiation switching in adult neural stem cells) show that defined inputs can switch IR/DI states to tune output kinetics. Integrating these findings, we propose an “Intron Retention Homeostat” (IR-Homeostat) model in which cells sense deviations from physiological set points and implement feedback control of gene output through switchable IR/DI regulation. This framework positions IR not only as a robust state readout for stratification, treatment response prediction, and pharmacodynamic profiling, but also as a tractable entry point to identify the molecular sensors and mediators that couple homeostatic signals to RNA processing control. Full article

Background: Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of urinary tract infections (UTIs) worldwide. The emergence of strains combining high virulence with multidrug resistance (MDR) poses a significant challenge to public health. This study aimed to characterize the phylogenetic distribution, virulence profiles, and antimicrobial susceptibility of UPEC isolates recovered from patients in the metropolitan area of Buenos Aires (AMBA), Argentina. Methodology: Phylogenetic groups, the ST131 lineage, and virulence-associated genes were identified using PCR-based assays. Antimicrobial susceptibility testing (AST) was performed using automated methods and extended-spectrum beta-lactamase (ESBL) production was confirmed using the double-disk synergy test. Colistin (COL) resistance was evaluated by Colistin Drop Test and PCR screening for the mcr-1 (mobile colistin resistance gene 1). Biofilm formation was detected by the Tissue Culture Plate (TCP) method, whereas phenotypic virulence factors (VF) were assessed with Congo Red agar, hemagglutination, and hemolysis assays. Results: Phylogenetic groups B2 (43.8%) and D (26.7%), typically associated with extraintestinal infections, were the most frequent. The high-risk clone B2-ST131 was detected in 6.7% of isolates. Biofilm production was observed in 92.4% of the isolates, with curli fimbriae (87.6%) being the most frequently expressed VF. The highest resistance rates were observed for ampicillin (62.1%), ampicillin-sulbactam (39.8%), and trimethoprim-sulfamethoxazole (25.2%). Interestingly, 3.8% of isolates exhibited colistin resistance, despite the absence of the mcr-1 gene. Conclusions: This study highlights the detection of MDR-UPEC isolates that showed strong resistance to fluoroquinolones and were ESBL producers with high virulence in Argentina, justifying future research encompassing genomic and epidemiological monitoring of local UPEC, which is essential for managing infections and developing new therapeutic and preventive measures. Full article

(1) Background: The search for new polymodal antioxidants to correct oxidative stress of various origins and its consequences remains one of the most pressing and rapidly developing areas of biomedical research. (2) Methods: Hydrogen peroxide and hydroxyl radical detection, induced luminescence assay, ELISA for 8-oxoguanine detection, animal survival, blood cell count, micronucleus test, and PCR were used. (3) Results: 2R,3R-trans-dihydroquercetin (DHQ) was shown to reduce the amount of hydrogen peroxide and hydroxyl radicals formed during water radiolysis, leading to reduced damage to biomolecules. DHQ is a radioprotector, most effective at a dose of 300 mg/kg administered 15 min before radiation exposure. The dose reduction factor is 1.22. DHQ administration reduces the severity of radiation-induced leukopenia and thrombopenia by protecting red bone marrow cells. The mechanism of DHQ’s radioprotective action is fundamentally different from that of classical stress response inducers and is based on the normalization of the target cell transcriptional profile, rather than its hyperstimulation. (4) Conclusions: DHQ’s ability to restore the expression of antioxidant defense, DNA repair, and apoptotic genes to physiological levels under radiation exposure allows it to be considered a promising pharmacological agent for the correction of radiation-induced damage to normal tissues. Full article

Agapanthus africanus (L.) Hoffmanns. is a medicinal plant traditionally used in South Africa for its promise as a source of bioactive compounds with anticancer properties. This study aimed to investigate the apoptotic effects of A. africanus fractions on cancer cell lines and to identify the bioactive phytochemical constituents using gas chromatography-mass spectrometry analysis. To test for cytotoxicity, MCF-7, A549, and HeLa cancer cells were treated with crude extract, n-hexane, n-butanol, dichloromethane, and aqueous fractions of A. africanus extracts at different concentrations (0.00–1000 µg/mL). Total apoptosis was quantified using Annexin V/PI staining. The 4′,6-diamidino-2-phenylindole was used to detect nuclear morphological changes and the Caspase-GLO 3/7 assay was employed to check the caspase activation in the cancer cells. Expression of apoptosis-related (caspase-3, bax, bcl-2) genes was evaluated using real time-polymerase chain reaction. The crude extract of A. africanus exhibited dose-dependent cytotoxicity against MCF-7, A549, and HeLa cells, with IC₅₀ values of 130 µg/mL, 380 µg/mL, and <125 µg/mL, respectively. Among the tested fractions, the n-butanol fraction showed cytotoxicity towards MCF-7 cells with an IC₅₀ value of <870 µg/mL. In contrast, n-hexane, dichloromethane and the aqueous fractions exhibited higher IC₅₀ values against cancer cells. Flow cytometry analysis, which was applied to quantify total apoptosis, revealed that the crude extract of A. africanus induced apoptosis by (~60%) compared to the n-butanol fraction, which exhibited a moderate apoptotic effect (~27%). DAPI nuclear staining showed nuclear shrinkage and chromatin condensation in the MCF-7 cell line, whereas in Caspase-GLO 3/7, the crude extract and n-butanol fraction resulted in significant luminescence, indicating activation of caspase-3/7. Caspase-3/7 analysis showed A. africanus treatments produced varying levels of apoptotic activation. The crude extract increased caspase activity by 2.9-fold, while the n-butanol fraction induced a 1.7-fold rise compared with untreated cells. GC-MS chromatograms detected and identified 16 compounds in the fractionated n-butanol and 23 compounds from the crude extract of A. africanus. The major compounds identified from the n-butanol fraction included n-hexadecanoic acid; α-tocopherol and 9,12,15-octadecatrienoic acid, while the GC–MS profile of the crude extract was dominated by 6,10,14-trimethylpentadecan-2-one; 1,3,5-Triphenylcyclohexane and phytol. The study indicates the pro-apoptotic potential of A. africanus, particularly in its crude form, supporting its ethnopharmacological use and suggesting its relevance as a candidate for anticancer drug discovery. Full article

Myo-inositol (MI) is recognized as a potential stress regulator capable of alleviating abiotic stress. The objective of this study is to analyze the role of MI in the salt stress response of Daucus carota L. and its potential mechanisms. “Hongxin Qicun” carrot seedlings were subjected to five treatments: control; salt stress (50 mM NaCl); and salt stress combined with 50, 100, or 200 μM of MI. Through an integrated approach combining physiological assays, non-invasive micro-test technology (NMT), and gene expression profiling, we found that salt stress severely inhibited seedling growth, disrupted K⁺/Na⁺ homeostasis, and triggered excessive H₂O₂ accumulation. Exogenous MI application mitigated these salt-induced damages, with 100 μM MI exerting the optimal effect. MI enhanced Na⁺ efflux and reduced K⁺ efflux in carrot roots under salt stress. Inhibitor experiments indicated that MI-promoted Na⁺ efflux relies on active transport via the plasma membrane (PM) Na⁺/H⁺ antiporter system, and qRT-PCR analysis showed that this response was accompanied by the upregulation of DcSOS1. Furthermore, MI contributes to K⁺ homeostasis by synergistically modulating PM H⁺-ATPase and high-affinity potassium transporters. The established proton gradient helps reduce salt-induced K⁺ loss through depolarization-activated potassium channels and non-selective cation channels. MI treatment decreased electrolyte leakage, malondialdehyde content, and H₂O₂ accumulation by enhancing the activities of the plant antioxidant defense system. Meanwhile, MI upregulated the expression of myo-inositol oxygenase (DcMIOXs) genes, which may contribute to osmotic balance maintenance and facilitate ROS scavenging. In conclusion, exogenous MI alleviates salt-induced physiological disorders in Daucus carota L. by coordinately regulating K⁺/Na⁺ and ROS homeostasis, with 100 μM identified as the optimal concentration for this effect. Full article

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article

Tomato fruit rot severely impacts yield and quality, causing economic losses. This study aimed to identify the pathogenic fungi associated with post-harvest tomato fruit rot and characterize the transcriptomic responses of tomatoes. Pathogens were isolated from diseased tomato fruit tissues and identified using morphology, phylogenetic analysis, and in vitro pathogenicity tests. The genome of Cladosporium oxysporum Co-1 was assembled and annotated. RNA-seq analysis was used to profile transcriptional changes in tomatoes infected with C. oxysporum Co-1, with RT-qPCR validating the RNA-seq data and spectrophotometric assays analyzing the host physiological responses. Three pathogenic fungi were isolated. Colonies of C. oxysporum exhibited a near-circular shape, with colonies transitioning from an olive-green center to gray-green at the edges, and based on ITS, β-tubulin, and EF-1α gene sequences, this isolate exhibited 99% identity with C. oxysporum. The other two fungal isolates were identified as Alternaria alternata and Fusarium incarnatum, respectively, based on morphological and multi-locus sequence analysis. All three strains induced fruit rot and browning in tomatoes, confirming their pathogenicity. The genome size of C. oxysporum Co-1 was 34,515,558 bp, comprising 52 scaffolds with a GC content of 52.82%, and encoding 10,081 protein-coding genes. RNA-seq analysis showed dynamic gene expression changes in tomatoes infected with strain A, with differentially expressed genes enriched in pathogenicity-related pathways. Spectrophotometric assays revealed that peroxidase and superoxide dismutase activities decreased initially followed by an increase post-inoculation with C. oxysporum, indicating that tomatoes defend against pathogen infection through the antioxidant enzyme system. These findings revealed the pathogenic fungi were associated with post-harvest tomato rot disease, provided genomic resources for C. oxysporum, and provided insight into the host’s response to this strain. Full article

Aging is associated with a high prevalence of insomnia, which is linked to somatic and neuropsychiatric diseases, as well as metabolic and immunological dysfunction. This study aims to identify alterations in the transcriptome profiles and functional metabolic pathways in older adults with different types of sleep disorders. This cross-sectional study included 1002 participants (60–90 years) who were screened for sleep disorders using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Two types of sleep disorders were identified in the study cohort, i.e., sleep onset insomnia and sleep maintenance insomnia. Both types of insomnia were further analyzed for associations with clinical characteristics, laboratory testing results, and socioeconomic backgrounds. The transcriptomic profiles of peripheral blood samples were examined in 236 individuals, supplemented with differential gene and dsRNA expression analyses (DESeq2). Both sleep onset insomnia and middle insomnia were associated with depression, chronic pain syndrome, and osteoarthritis, while only middle insomnia was associated with cardiometabolic diseases. No associations were observed between sleep onset insomnia or reduced sleep duration and transcriptomic profiles. In contrast, 244 genes were differentially expressed in patients with middle insomnia, indicating the activation of pathways related to viral infection response and inhibition of protein synthesis. Additionally, differential expression analysis of double-stranded RNA (dsRNA) identified 2139 significant changes. Middle insomnia in older adults is associated with transcriptomic changes indicative of an activated antiviral immune response, likely resulting from changes in dsRNA expression levels. The chronic inflammation arising from these transcriptomic alterations may underlie the observed association between middle insomnia and cardiometabolic conditions. Full article

Myocarditis and inflammatory cardiomyopathy are inflammatory diseases of the heart muscle that can have both infectious and non-infectious causes. They can be caused by an unresolved viral infection or other infection, or they can be autoimmune, toxic, or allergic in nature. The specific identification of the pathogen and/or confirmation of inflammation can only be achieved through direct tissue analysis using endomyocardial biopsy (EMB), as neither detection of the virus nor assessment of the quality and intensity of the inflammation is possible using non-invasive methods. Accordingly, the removal and analysis of an EMB is considered the diagnostic gold standard in international guidelines and statements. The sudden onset of atypical angina pectoris and initially exertion-dependent dyspnea, as well as arrhythmias, pericardial effusion, and progressive symptoms of heart failure, indicate an acute inflammatory process of the myocardium. In addition, nonspecific symptoms such as fatigue and reduced physical performance may also occur. Diagnostic evaluation includes an electrocardiogram (ECG), cardiac imaging, and laboratory tests. The analysis of the EMB is crucial for a definitive diagnosis and thus for the initiation of an etiology-based, specific and personalized therapy. This includes histological and immunohistochemical inflammation diagnostics as well as molecular virological diagnostics. These enable both the detection of viruses and the assessment of transcriptional virus activity. New analyses using metagenomic next generation sequencing (NGS) techniques provide insights of enormous diagnostic and therapeutic relevance. This applies both to the spectrum of detectable pathogens and to the possibility of confirming transcriptional viral activity. In addition, gene expression profiling enables the differentiation of specific forms of myocardial inflammation (e.g., giant cell myocarditis, cardiac sarcoidosis, and eosinophilic myocarditis) and reduces the influence of “sampling errors” in focal inflammatory processes. The treatment of heart failure or ventricular arrhythmias is always symptomatic according to general evidence-based guidelines. In severe cases, mechanical circulatory support or even a heart transplant may be necessary. Patients with histologically confirmed myocardial inflammation or intramyocardial viral infection can be offered specific, causal, and personalized therapy. These patients can be successfully treated with immunosuppressive or antiviral therapy, which significantly improves the prognosis of the disease. Full article