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Keywords = multiorgan involvement

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9 pages, 477 KiB  
Opinion
Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection
by Balázs Sonkodi
Cells 2025, 14(15), 1182; https://doi.org/10.3390/cells14151182 - 31 Jul 2025
Abstract
The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the [...] Read more.
The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
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11 pages, 1118 KiB  
Case Report
Infective Endocarditis with Gerbode Defect and DRESS Syndrome: A Rare Case Report
by Corina Ureche, Diana Lavinia Moldovan, Ionel Vița, Valeria Guila and Teodora Nicola-Varo
Reports 2025, 8(3), 127; https://doi.org/10.3390/reports8030127 - 31 Jul 2025
Abstract
Background and Clinical Significance: Infective endocarditis (IE) is a serious condition with rising incidence, frequently caused by Staphylococcus aureus. However, cases involving rare congenital anomalies such as Gerbode’s defect are uncommon. Case Presentation: This report presents the first documented case of IE [...] Read more.
Background and Clinical Significance: Infective endocarditis (IE) is a serious condition with rising incidence, frequently caused by Staphylococcus aureus. However, cases involving rare congenital anomalies such as Gerbode’s defect are uncommon. Case Presentation: This report presents the first documented case of IE in a patient with a congenital Gerbode defect complicated by DRESS syndrome—a severe, drug-induced hypersensitivity reaction typically triggered by antibiotics like oxacillin. A 65-year-old woman developed infective endocarditis involving vegetations on the cardiac device lead, the tricuspid valve, and adjacent to a Gerbode defect. The diagnosis was confirmed by positive blood cultures and echocardiographic findings. She received treatment with oxacillin. Subsequently, she exhibited clinical features consistent with DRESS syndrome, including rash, eosinophilia, and multi-organ involvement. Rapid recognition and management, including corticosteroid therapy and antibiotic modification, led to clinical improvement. Conclusions: This case highlights the importance of vigilance for DRESS syndrome in prolonged antibiotic therapy for IE, especially in the context of rare congenital cardiac anomalies. In addition, guidelines are needed to optimize the diagnosis and treatment of this potentially lethal complication. Full article
(This article belongs to the Section Cardiology/Cardiovascular Medicine)
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10 pages, 1604 KiB  
Article
Anifrolumab Attenuates Follicular Helper T Cell Activation in Patients with Systemic Lupus Erythematosus
by Ádám Diós, Ágnes Gyetvai, Gábor Papp and Tünde Tarr
Int. J. Mol. Sci. 2025, 26(15), 7397; https://doi.org/10.3390/ijms26157397 (registering DOI) - 31 Jul 2025
Abstract
Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects [...] Read more.
Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects of inhibited type I IFN signaling on circulating follicular helper T subsets (TFH), follicular regulatory T cells (TFR), and B lymphocyte subpopulations, reflecting the ongoing germinal center reactions in SLE patients. Peripheral blood samples were obtained from ten SLE patients before the initiation of anifrolumab treatment, and at months 6 and 12 of the intervention period. Flow cytometry analysis was performed to assess the frequencies of circulating TFH cell subsets, TFR cells, and certain B cell subpopulations. Serological parameters, including autoantibody levels and complement components, were determined as part of the routine diagnostic evaluation. We observed a significant and sustained reduction in the percentage of activated circulating TFH cells. Notably, the frequency of CXCR3CCR6+ TFH17 cells decreased, whereas the proportion of CXCR3+CCR6 TFH1 cells increased significantly. Furthermore, the proportion of the IgDCD27 double-negative B lymphocytes was also significantly reduced. These findings suggest that anifrolumab therapy attenuates TFH cell activation, which may contribute to its clinical efficacy by modulating germinal center responses in SLE. Full article
(This article belongs to the Special Issue Drug Therapy of Systemic Lupus Erythematosus)
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21 pages, 7017 KiB  
Article
Chronic Heat Stress Caused Lipid Metabolism Disorder and Tissue Injury in the Liver of Huso dauricus via Oxidative-Stress-Mediated Ferroptosis
by Yining Zhang, Yutao Li, Ruoyu Wang, Sihan Wang, Bo Sun, Dingchen Cao, Zhipeng Sun, Weihua Lv, Bo Ma and Ying Zhang
Antioxidants 2025, 14(8), 926; https://doi.org/10.3390/antiox14080926 - 29 Jul 2025
Viewed by 93
Abstract
High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts [...] Read more.
High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts of heat stress on the liver metabolism functions in Huso dauricus. In this study, we set one control group (19 °C) and four high-temperature treatment groups (22 °C, 25 °C, 28 °C, 31 °C) with 40 fish in each group for continuous 53-day heat exposure. Histological analysis, biochemical detection, and transcriptome technology were used to explore the effects of heat stress on the liver structure and functions of juvenile Huso dauricus. It suggested heat-stress-induced obvious liver injury and reactive oxygen species accumulation in Huso dauricus with a time/temperature-dependent manner. Serum total protein, transaminase, and alkaline phosphatase activities showed significant changes under heat stress (p < 0.05). In addition, 6433 differentially expressed genes (DEGs) were identified based on the RNA-seq project. Gene Ontology enrichment analysis showed that various DEGs could be mapped to the lipid-metabolism-related terms. KEGG enrichment and immunohistochemistry analysis showed that ferroptosis and FoxO signaling pathways were significantly enriched (p < 0.05). These results demonstrated that thermal stress induced oxidative stress damage in the liver of juvenile Huso dauricus, which triggered lipid metabolism disorder and hepatocyte ferroptosis to disrupt normal liver functions. In conclusion, chronic thermal stress can cause antioxidant capacity imbalance in the liver of Huso dauricus to mediate the ferroptosis process, which would finally disturb the lipid metabolism homeostasis. In further research, it will be necessary to verify the detailed cellular signaling pathways that are involved in the heat-stress-induced liver function disorder response based on the in vitro experiment, while the multi-organ crosswalk mode under the thermal stress status is also essential for understanding the comprehensive mechanism of heat-stress-mediated negative effects on fish species. Full article
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8 pages, 855 KiB  
Case Report
Severe Malaria Due to Plasmodium falciparum in an Immunocompetent Young Adult: Rapid Progression to Multiorgan Failure
by Valeria Sanclemente-Cardoza, Harold Andrés Payán-Salcedo and Jose Luis Estela-Zape
Life 2025, 15(8), 1201; https://doi.org/10.3390/life15081201 - 28 Jul 2025
Viewed by 176
Abstract
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation [...] Read more.
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article
(This article belongs to the Section Medical Research)
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19 pages, 766 KiB  
Systematic Review
Molecular Mechanisms Underlying Inflammation in Early-Onset Neonatal Sepsis: A Systematic Review of Human Studies
by Anca Vulcănescu, Mirela-Anișoara Siminel, Anda-Lorena Dijmărescu, Maria-Magdalena Manolea, Sidonia-Maria Săndulescu, Virginia Maria Rădulescu, Valeriu Gheorman and Sorin-Nicolae Dinescu
J. Clin. Med. 2025, 14(15), 5315; https://doi.org/10.3390/jcm14155315 - 28 Jul 2025
Viewed by 220
Abstract
Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be [...] Read more.
Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes. Full article
(This article belongs to the Section Clinical Pediatrics)
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19 pages, 2212 KiB  
Review
Antiphospholipid Syndrome—Diagnostic and Methodologic Approach
by Agata Stańczewska, Karolina Szewczyk-Golec and Iga Hołyńska-Iwan
Metabolites 2025, 15(8), 500; https://doi.org/10.3390/metabo15080500 - 27 Jul 2025
Viewed by 413
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and [...] Read more.
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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16 pages, 3032 KiB  
Article
Severe Scrub Typhus with Acute Kidney Injury: Urine PCR Evidence from an East Coast Malaysian Cluster
by Siti Roszilawati Ramli, Nuridayu Arifin, Mohd Fahmi Ismail, Shirley Yi Fen Hii, Nur Suffia Sulaiman, Ernieenor Faraliana Che Lah and Nik Abdul Hadi Nik Abdul Aziz
Trop. Med. Infect. Dis. 2025, 10(8), 208; https://doi.org/10.3390/tropicalmed10080208 - 25 Jul 2025
Viewed by 326
Abstract
Background: Scrub typhus (ST) is caused by Orientia tsutsugamushi (OT) infection, which is transmitted to humans through the bites of infected chiggers. The clinical presentations range from mild to life-threatening multi-organ dysfunction. This report describes a cluster of ST cases involving five oil [...] Read more.
Background: Scrub typhus (ST) is caused by Orientia tsutsugamushi (OT) infection, which is transmitted to humans through the bites of infected chiggers. The clinical presentations range from mild to life-threatening multi-organ dysfunction. This report describes a cluster of ST cases involving five oil palm estate workers in Pekan district, Pahang, Malaysia. Methods: The clinical history, laboratory, and entomological investigation were conducted on the patients, including the index case and four suspected cases in the cluster. Polymerase chain reaction (PCR) tests for OT and genotyping were performed on the patients’ blood and urine samples. Serological testing by indirect immunoperoxidase (IIP) test against Rickettsial diseases was also conducted. Principal Findings: Patients presented with fever, myalgia, headache, rash, cough, and eschar. The index case developed severe ST complicated by acute kidney injury (AKI) and respiratory distress, requiring intubation and ventilation at the intensive care unit of a tertiary hospital. ST was confirmed through PCR analysis of a urine sample, showcasing a novel diagnostic approach. The other four cases were confirmed by a four-fold rise in immunoglobulin G (IgG) antibody titers. Conclusions: oil palm estate workers are at high risk for chigger exposure in Malaysia. Awareness among clinicians and the public of ST is crucial for effective prevention, accurate diagnosis, and optimal management. Full article
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14 pages, 971 KiB  
Article
High Voltage and Train-Surfing Injuries: A 30-Year Retrospective Analysis of High-Voltage Trauma and Its Impact on Cardiac Biomarkers
by Viktoria Koenig, Maximilian Monai, Alexandra Christ, Marita Windpassinger, Gerald C. Ihra, Alexandra Fochtmann-Frana and Julian Joestl
J. Clin. Med. 2025, 14(14), 4969; https://doi.org/10.3390/jcm14144969 - 14 Jul 2025
Viewed by 268
Abstract
Background: High-voltage electrical injuries (HVEIs) represent a complex and life-threatening entity, frequently involving multi-organ damage. While traditionally linked to occupational hazards, train surfing—riding on moving trains—and train climbing—scaling stationary carriages—have emerged as increasingly common causes among adolescents. Popularized via social media, these [...] Read more.
Background: High-voltage electrical injuries (HVEIs) represent a complex and life-threatening entity, frequently involving multi-organ damage. While traditionally linked to occupational hazards, train surfing—riding on moving trains—and train climbing—scaling stationary carriages—have emerged as increasingly common causes among adolescents. Popularized via social media, these behaviors expose individuals to the invisible danger of electric arcs from 15,000-volt railway lines, often resulting in extensive burns, cardiac complications, and severe trauma. This study presents a 30-year retrospective analysis comparing cardiac biomarkers and clinical outcomes in train-surfing injuries versus work-related HVEIs. Methods: All patients with confirmed high-voltage injury (≥1000 volts) admitted to a Level 1 burn center between 1994 and 2024 were retrospectively analyzed. Exclusion criteria comprised low-voltage trauma, suicide, incomplete records, and external treatment. Clinical and laboratory parameters—including total body surface area (TBSA), Abbreviated Burn Severity Index (ABSI), electrocardiogram (ECG) findings, intensive care unit (ICU) and hospital stay, mortality, and cardiac biomarkers (creatine kinase [CK], CK-MB, lactate dehydrogenase [LDH], aspartate transaminase [AST], troponin, and myoglobin)—were compared between the two cohorts. Results: Of 81 patients, 24 sustained train-surfing injuries and 57 were injured in occupational settings. Train surfers were significantly younger (mean 16.7 vs. 35.2 years, p = 0.008), presented with greater TBSA (49.9% vs. 17.9%, p = 0.008), higher ABSI scores (7.3 vs. 5.1, p = 0.008), longer ICU stays (53 vs. 17 days, p = 0.008), and higher mortality (20.8% vs. 3.5%). ECG abnormalities were observed in 51% of all cases, without significant group differences. However, all cardiac biomarkers were significantly elevated in train-surfing injuries at both 72 h and 10 days post-injury (p < 0.05), suggesting more pronounced cardiac and muscular damage. Conclusions: Train-surfing-related high-voltage injuries are associated with markedly more severe systemic and cardiac complications than occupational HVEIs. The significant biomarker elevation and critical care demands highlight the urgent need for targeted prevention, public awareness, and early cardiac monitoring in this high-risk adolescent population. Full article
(This article belongs to the Section Cardiovascular Medicine)
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15 pages, 626 KiB  
Review
Prediction of Mortality by Clinical Laboratory Parameters in Severe Fever with Thrombocytopenia Syndrome: A Meta-Analysis
by Shicui Yan, Xuebin Ding, Qiao Gao, Lili Zhao, Cong Li, Zhenlu Sun and Xuejun Ma
Trop. Med. Infect. Dis. 2025, 10(7), 193; https://doi.org/10.3390/tropicalmed10070193 - 9 Jul 2025
Viewed by 304
Abstract
Background: This study intended to fully assess the predictive efficiency of different clinical laboratory parameters for the mortality risk in severe fever with thrombocytopenia syndrome (SFTS). Methods: We systematically searched the Web of Science, PubMed, Cochrane Library, and Embase up to 13 December [...] Read more.
Background: This study intended to fully assess the predictive efficiency of different clinical laboratory parameters for the mortality risk in severe fever with thrombocytopenia syndrome (SFTS). Methods: We systematically searched the Web of Science, PubMed, Cochrane Library, and Embase up to 13 December 2024 for studies on the association of laboratory parameters with SFTS mortality. Two investigators were independently responsible for the study screening and data extraction, and they assessed the study quality using the Newcastle–Ottawa Scale (NOS). Stata17.0 was adopted for the meta-analyses. Results: We finally included 33 observational studies involving 9502 participants (1799 deaths and 7703 survivors). The results showed that increases in the viral load (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.56–2.38), neutrophil-to-lymphocyte ratio (hazard ratio (HR) 1.31, 95% CI 1.13–1.51), neutrophil percentage (HR 1.02, 95% CI 1.01–1.03), white blood cells (HR 1.06, 95% CI 1.01–1.11), activated partial thromboplastin time (OR 1.07, 95% CI 1.04–1.09), prothrombin time (OR 1.31, 95% CI 1.03–1.65), creatine kinase-myocardial band (OR 1.01, 95% CI 1.01–1.02), and procalcitonin (HR 1.27, 95% CI 1.10–1.47) greatly increased the SFTS mortality, while decreases in the lymphocyte percentage (HR 0.96, 95% CI 0.94–0.98), platelets (HR 0.98, 95% CI 0.97–0.99), and albumin (HR 0.91, 95% CI 0.86–0.96) also greatly increased the SFTS mortality; the results were all statistically significant (p < 0.05). Conclusion: Abnormalities of laboratory parameters (e.g., viral load, blood routine, coagulation, multi-organ dysfunction, and inflammation indicators) are good predictors of SFTS mortality, which can provide valuable references in clinical practice. Full article
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13 pages, 680 KiB  
Review
Microbiome Against the Background of the Complex Aetiology in Sarcoidosis—What Do We Already Know?
by Maciej Szymański, Katarzyna Góralska and Ewa Brzeziańska-Lasota
Life 2025, 15(7), 1069; https://doi.org/10.3390/life15071069 - 4 Jul 2025
Viewed by 362
Abstract
Sarcoidosis is a multi-organ, systemic disease of immunological origin. While its aetiology is unknown, it is believed to be influenced by genetic susceptibility, environmental factors, and autoimmunity. Recent research on the development and progression of sarcoidosis has focused increasingly on the role of [...] Read more.
Sarcoidosis is a multi-organ, systemic disease of immunological origin. While its aetiology is unknown, it is believed to be influenced by genetic susceptibility, environmental factors, and autoimmunity. Recent research on the development and progression of sarcoidosis has focused increasingly on the role of microorganisms. Changes in the respiratory tract microbiome, and hence the physiology of the respiratory tract, are believed to influence the course of sarcoidosis; this is not unlikely, as research indicates that the state of the microbiota inhabiting individual ontocenoses, such as the intestines or blood, may be related to the health of the entire body. This review therefore discusses the microbiological factors that are believed to be involved in the development of the disease; however, as the aetiological factors of sarcoidosis are diverse and are based on highly complex mechanisms, our analysis is restricted to only the most likely factors. Full article
(This article belongs to the Special Issue The Emerging Role of Microbiota in Health and Diseases)
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18 pages, 908 KiB  
Review
The Role of Protein Ubiquitination in the Onset and Progression of Sepsis
by Meng-Yan Chen, Yang Liu and Min Fang
Cells 2025, 14(13), 1012; https://doi.org/10.3390/cells14131012 - 2 Jul 2025
Viewed by 606
Abstract
Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, with complex pathophysiological mechanisms. As an important post-translational modification, protein ubiquitination exhibits multiple non-traditional functions in sepsis beyond its conventional role in protein degradation. Regulating the network of inflammatory cytokines, [...] Read more.
Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, with complex pathophysiological mechanisms. As an important post-translational modification, protein ubiquitination exhibits multiple non-traditional functions in sepsis beyond its conventional role in protein degradation. Regulating the network of inflammatory cytokines, the dynamic balance of immune cells and organ-specific protective pathways is deeply involved in the pathological process of sepsis. This review focuses on the unconventional roles of protein ubiquitination in sepsis, including its regulation of the inflammatory response, immune cell functions, and organ protection. It systematically summarizes the regulatory mechanisms of ubiquitination in the non-degradative activation of the nuclear factor kappa B (NF-κB) signaling pathway, the dynamic assembly of the NLRP3 inflammasome, the reprogramming of macrophage polarization, and the injuries of organs such as the heart, liver, and lungs. These processes demonstrate that ubiquitination serves as a pivotal nexus between immunological dysregulation and multi-organ impairment in sepsis. This review suggests that targeting non-degradative ubiquitination alterations may provide viable therapeutic options to mitigate excessive inflammation and organ failure in sepsis. Full article
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15 pages, 3067 KiB  
Article
The Whole Blood Transcriptomic Analysis in Sickle Cell Disease Reveals RUNX3 as a Potential Marker for Vaso-Occlusive Crises
by Safa Taha, Hawra Abdulwahab, Muna Aljishi, Ameera Sultan, Moiz Bakhiet, Salvatore Spicuglia and Mohamed Belhocine
Int. J. Mol. Sci. 2025, 26(13), 6338; https://doi.org/10.3390/ijms26136338 - 30 Jun 2025
Viewed by 371
Abstract
Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and [...] Read more.
Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance. Full article
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12 pages, 546 KiB  
Article
The Significance of Elevated sST2 in Children with Kawasaki Disease
by Zhaohua Yang, Yunming Xu, Yanqiu Chu, Jinghao Li and Hong Wang
Children 2025, 12(7), 868; https://doi.org/10.3390/children12070868 - 30 Jun 2025
Viewed by 196
Abstract
Objectives: Kawasaki Disease (KD) is an acute vasculitis associated with systemic inflammation. This study aimed to investigate the level and clinical significance of soluble ST2 (sST2) in children with KD. Methods: A retrospective analysis was conducted on 287 pediatric KD patients treated at [...] Read more.
Objectives: Kawasaki Disease (KD) is an acute vasculitis associated with systemic inflammation. This study aimed to investigate the level and clinical significance of soluble ST2 (sST2) in children with KD. Methods: A retrospective analysis was conducted on 287 pediatric KD patients treated at the Pediatric Cardiology Department of Shengjing Hospital, China Medical University, from November 2021 to December 2022. Patients were stratified into subgroups based on the presence of myocardial damage (MD), coronary artery lesions (CAL), multi-organ involvement (MOD; ≥3 organs) and/or intravenous immunoglobulin-resistant KD (IVIG-R KD). In each group, we analyzed the correlation between sST2 levels and various laboratory parameters, including white blood cell count (WBC), hemoglobin (HB), platelet count (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), N-terminal pro-brain natriuretic peptide (NT-pro BNP), D-dimer, and albumin (ALB). Results: Patients in the CAL group were significantly younger and predominantly male (p < 0.05). In the MD, CAL, MOD, and IVIG-R KD groups, levels of sST2, CRP, NT-pro BNP, and D-dimer were significantly higher than in their respective comparison groups (p < 0.05). sST2 showed weak positive correlations with WBC, CRP, IL-6, NT-pro BNP, and D-dimer, and weak negative correlations with HB and ALB (p < 0.05). sST2, HB, and IL-6 were identified as independent risk factors for MOD (p < 0.05). sST2 and HB were independent risk factors for IVIG-R KD (p < 0.05). Among acute-phase patients, four cases had sST2 levels > 200 ng/mL—all were classified as IVIG-R KD and MOD; three of these also developed coronary artery aneurysms (CAA). Conclusions: Elevated sST2 levels in the acute phase of KD may serve as a clinical indicator of IVIG-R KD, CAA, MOD, and MD. Full article
(This article belongs to the Special Issue Kawasaki Disease in Children: Advance and Challenges)
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19 pages, 2030 KiB  
Article
Presentation and Clinical Course of Leptospirosis in a Referral Hospital in Far North Queensland, Tropical Australia
by Hayley Stratton, Patrick Rosengren, Toni Kinneally, Laura Prideaux, Simon Smith and Josh Hanson
Pathogens 2025, 14(7), 643; https://doi.org/10.3390/pathogens14070643 - 28 Jun 2025
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Abstract
The case-fatality rate of severe leptospirosis can exceed 50%. This retrospective cohort study examined 111 individuals with laboratory-confirmed leptospirosis admitted to Cairns Hospital, a referral hospital in tropical Australia, between January 2015 and June 2024. We examined the patients’ demographic, clinical, laboratory and [...] Read more.
The case-fatality rate of severe leptospirosis can exceed 50%. This retrospective cohort study examined 111 individuals with laboratory-confirmed leptospirosis admitted to Cairns Hospital, a referral hospital in tropical Australia, between January 2015 and June 2024. We examined the patients’ demographic, clinical, laboratory and imaging findings at presentation and then correlated them with the patients’ subsequent clinical course. Severe disease was defined as the presence of pulmonary haemorrhage or a requirement for intensive care unit (ICU) admission. The patients’ median (interquartile range) age was 38 (24–55) years; 85/111 (77%) were transferred from another health facility. Only 13/111 (12%) had any comorbidities. There were 63/111 (57%) with severe disease, including 56/111 (50%) requiring ICU admission. Overall, 56/111 (50%) required vasopressor support, 18/111 (16%) needed renal replacement therapy, 14/111 (13%) required mechanical ventilation and 2/111 (2%) needed extracorporeal membrane oxygenation. Older age—but not comorbidity—was associated with the presence of severe disease. Hypotension, respiratory involvement, renal involvement and myocardial injury—but not liver involvement—frequently heralded a requirement for ICU care. Every patient in the cohort survived to hospital discharge. Leptospirosis can cause multi-organ failure in otherwise well young people in tropical Australia; however, patient outcomes are usually excellent in the country’s well-resourced health system. Full article
(This article belongs to the Section Bacterial Pathogens)
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