Search Results (1,141)

The emergence of bacterial strains resistant to available antibiotics due to overprescription has prompted a search for alternative treatments. Among the most promising is baicalin, a flavonoid extracted from the roots of Scutellaria baicalensis. Roots, the primary natural source of baicalin, have been extensively explored using emerging extraction technologies such as ultrasonic-assisted extraction and supercritical fluid extraction. These methods offer significant advantages over traditional reflux extraction for baicalin preparation, including shorter extraction times, lower energy consumption, and improved environmental sustainability. Baicalin exhibits remarkable antibacterial activity in vitro and has demonstrated therapeutic efficacy against gastrointestinal infections, meningitis, pulmonary diseases, and sepsis, among other infectious disorders, in animal models. Documented mechanisms of action include disrupting the Escherichia coli membrane, downregulating quorum-sensing gene expression in Pseudomonas aeruginosa, and inhibiting host inflammatory pathways such as PI3K/Akt/NF-κB. However, its clinical translation faces several bottlenecks, including reliance on animal experiment data, low bioavailability, and regulatory compliance issues. This review compares baicalin extraction yields from different natural sources, summarizes the advantages and disadvantages of various extraction technologies, analyzes possible mechanisms of action in treating different bacterial diseases, and discusses outstanding challenges and best strategies for expanded clinical use against bacterial infection. Our aim is to provide a valuable reference for future research and clinical applications. Full article

The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article

Background: Fusobacterium species are anaerobic Gram-negative bacilli that are part of the normal oropharyngeal and gastrointestinal flora. Although rare, they can cause infective endocarditis (IE), a severe condition with high morbidity. The clinical characteristics, treatment strategies, and outcomes of IE caused by Fusobacterium spp. remain incompletely defined. This systematic review aimed to synthesize available data on Fusobacterium IE and compare its features with IE caused by other pathogens. Methods: We conducted a systematic literature search in PubMed, Scopus, and the Cochrane Library up to 27 February 2025, using the terms “Fusobacterium” and “endocarditis.” Eligible studies included case reports or series describing adult or pediatric patients with Fusobacterium-associated IE. Data were extracted on demographics, risk factors, clinical features, microbiology, treatment, and outcomes. Results: A total of 21 studies (all case reports) involving 21 patients were included. The median age was 48 years, and 85.7% were male. Poor dental hygiene or recent dental work was the most common predisposing factor (47.6%). The mitral valve was most frequently affected (44.4%). Fever and sepsis were reported in nearly all cases, and embolic phenomena occurred in 81%. The most commonly isolated species were F. necrophorum (47.6%) and F. nucleatum (42.9%). Treatment commonly included metronidazole (61.9%), while surgical management was required in 23.8%. All-cause and infection-attributable mortality were both 9.5%. Conclusions: Fusobacterium IE predominantly affects younger males and is often linked to oral sources. This disease is associated with a high risk of systemic complications but seems to have a lower mortality compared to IE from other pathogens, including other anaerobic bacteria. Early diagnosis and appropriate antimicrobial treatment are of utmost importance for optimal outcomes. Further research is required to guide evidence-based management of this rare but serious infection. Full article

Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including negative pressure wound therapy, antibiotic-based infection control, and wound debridement, have been developed to treat skin wounds. However, these approaches primarily target local wound conditions and offer only short-term relief, not achieving sustained functional regeneration. Stem cell-based therapy has emerged as an alternative therapeutic method for skin wound treatment owing to its ability to suppress inflammation, stimulate angiogenesis, and promote cellular proliferation. However, the low post-transplantation survival rate of stem cells remains a major limitation. Exosomes, nanosized extracellular vesicles, transport proteins, lipids, mRNAs, and miRNAs and mediate regenerative functions, including anti-inflammatory effects, angiogenesis promotion, and extracellular matrix remodeling. Stem cell-derived exosomes (SC-Exos) offer several advantages over their parent cells, including greater stability, lower immunogenicity, absence of tumorigenic risks, and ease of storage and distribution. These attributes render SC-Exos particularly attractive for cell-free regenerative therapies. In this review, we introduce exosomes derived from various types of stem cells and explore their therapeutic applications in skin wound regeneration. Full article

Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. Methods: This retrospective cohort study included 64 adult patients with severe sepsis or septic shock who received at least one session of PMX-HP in a 25-bed tertiary medical ICU in Taiwan between July 2013 and December 2019. Demographic, clinical, microbiological, and treatment data were extracted. The primary outcome was 28-day mortality. Prognostic factors were analyzed using logistic regression. Results: The mean age was 66.1 ± 12.3 years; 67.2% were male. Pneumonia (29.7%) and intra-abdominal infection (18.8%) were the most common sources of sepsis, with E. coli and K. pneumoniae as leading pathogens. Median APACHE II score at ICU admission was 26 (IQR 21–32), and 79.7% received two PMX-HP sessions. The 28-day mortality rate was 46.9%, with ICU and hospital mortality both 53.1%. Non-survivors were older, had higher APACHE II scores, and more frequent use of continuous renal replacement therapy (CRRT). Positive changes in vasoactive-inotropic score (VIS) after PMX-HP were also more common among non-survivors. Multivariate analysis identified advanced age, higher APACHE II score, and CRRT requirement as independent predictors of mortality. Conclusions: In this real-world Asian ICU cohort, PMX-HP was used mainly for severe cases with a high disease burden and Gram-negative predominance. Despite its frequent use, overall mortality remained high. Prognosis was primarily determined by underlying disease severity, organ dysfunction (especially renal failure), and persistent hemodynamic instability. In this high-severity cohort, mortality appeared to be primarily driven by baseline organ dysfunction and persistent hemodynamic instability; PMX-HP session number or sequencing showed no association with survival. Given the absence of a contemporaneous non-PMX-HP control group, mortality observations in this cohort cannot be causally attributed to PMX-HP and should be interpreted with caution as hypothesis-generating rather than definitive evidence of efficacy. Further multicenter studies are needed to clarify the optimal role of PMX-HP in modern sepsis management. Full article

Continuous extradural infusions (CEIs) provide sustained analgesia, avoiding fluctuations seen with bolus administrations. An extradural catheter was placed in a cat with severe abdominal trauma following a vehicular accident. To provide sustained pain relief, a CEI of 0.5% ropivacaine at 0.18 mg/kg/h or 0.036 mL/kg/h was initiated, resulting in improved analgesia, as shown by lower scores on both the Feline Grimace Scale (FGS) and the Glasgow Composite Measure Pain Scale-Feline (CMPS-Feline). During treatment, the cat developed hypersalivation, which persisted after catheter removal at 72 h. Eventually, the cat’s condition deteriorated, with signs of sepsis leading to euthanasia due to a poor prognosis. Potential contributors to the cat’s decline included systemic infection, local anaesthetic systemic toxicity, or opioid-related effects. This report describes the placement of an extradural catheter in a cat, highlighting the potential of CEI in feline pain management while emphasising the need for further research on its pharmacokinetics and safety. Full article

Background/Objectives: Despite overlapping inflammatory responses and frequent culture-negative results in severe burn patients, early and accurate sepsis diagnosis remains challenging. We aimed to evaluate the diagnostic performance of seven candidate biomarkers and their clinical utility, particularly in culture-negative cases. Methods: We conducted a prospective diagnostic accuracy study (January 2021–December 2022; N = 221) in the burn intensive care unit, applying a two-step feature selection to 41 candidate variables. Seven top biomarkers—presepsin, procalcitonin (PCT), albumin, C-reactive protein (CRP), prothrombin time (PT), hematocrit (Hct), and D-dimer—were measured at the moment of clinical sepsis suspicion, concurrently with blood cultures and prior to empirical antibiotic administration, within ±2 h of Sequential Organ Failure Assessment (SOFA). Diagnostic performance was evaluated using a Receiver Operating Characteristic (ROC) curve analysis to determine the area under the curve (AUC), Youden index-derived cut-offs, decision curve analysis, and Net Reclassification Improvement (NRI). Results: Presepsin achieved the highest overall AUC (0.810; 95% CI, 0.742–0.878) and outperformed other markers in culture-negative cases (AUC, 0.846 vs. 0.604; p = 0.015). In the decision curve analysis, presepsin and PCT maintained the largest net benefits at high thresholds, although PT, D-dimer, and Hct also retained smaller positive benefits. Patients were stratified into high- vs. low-risk groups for survival analysis using Youden index cut-offs; Cox regression confirmed PCT (Hazard Ratio 3.78; p < 0.001) and PT (HR 2.12; p = 0.018) as a significant mortality predictor, with presepsin showing borderline significance (HR 3.14; p = 0.055). Conclusions: The high rate of culture-negative sepsis reflects early antibiotic use suppressing culture yield rather than resistance patterns alone. Presepsin’s rapid rise and preserved accuracy under pre-sampling antibiotics suggest its value for early sepsis detection and antimicrobial stewardship. Future work will incorporate polymicrobial and multidrug-resistant bloodstream infection profiles to refine biomarker utility. Full article

Background and Clinical Significance: Anaerococcus tetradius (A. tetradius) and Gardnerella vaginalis (G. vaginalis) are rare etiological factors for postpartum endometritis and are typically associated with bacterial vaginosis. However, in some cases, G. vaginalis and A. tetradius can cause serious postpartum endometritis with complications such as sepsis. Case Presentation: 26-year-old pregnant woman expecting monochorionic diamniotic twins presented to the hospital at 35 weeks and 3 days of gestation and two male infants were delivered via the Cesarean section. On the fifth day after delivery, the patient began to complain of intense abdominal pain, a fever of 37.9 °C, and overall weakness. Blood tests revealed neutrophilic leukocytosis, increased C-reactive protein (CRP) of 225.4 mg/L. Upon examination, abdominal distension, tenderness on palpation, and positive symptoms of peritoneal irritation were present and the site of the abdominal incision was inflamed with flowing foul-smelling greenish pus. Ultrasound examination revealed free fluid collection in the peritoneal cavity, under the liver, and around the uterus. Later, the condition of the patient worsened with progressing hypotension and respiratory distress. As a result, suppurative peritonitis and sepsis was suspected and the patient underwent urgent total hysterectomy without oophorectomy. Acute endometritis, focal myometritis, and chronic cervicitis were concluded from histopathological examination of the removed uterus. Microbiological tests showed the most abundant growth of A. tetradius in the wound cultures and great abundance of G. vaginalis in the abdominal cavity cultures. After trying three different treatment schemes and difficulties with determining the antibiotic sensitivity tests for pathogens, the antibacterial therapy was escalated to Meropenem, which was found to be effective, and the patient was discharged home. Conclusions: This case report highlights the severity of complications of postpartum endometritis that can be caused by rare pathogens (such as G. vaginalis and A. tetradius), and strategies for how to manage it. The clinical presentation of a patient should be monitored closely for several days after Cesarean section and if endometritis is suspected, microbiological cultures are necessary to determine the cause of infection and implement an appropriate treatment. Full article

Background: Larval debridement therapy is used to cleanse necrotic tissue wounds and/or decontaminate wounds that are not amenable to standard therapies. Methods: A patient was diagnosed with septic shock and multiple organ failure caused by Streptococcus pyogenes after thyroidectomy (the patient had experienced contact with a child with scarlet fever six days before admission to the hospital). As a result of systemic infection, numerous necrotic skin lesions appeared, which involved the surgical site, chest and scalp. A tracheocutaneous fistula was confirmed. Due to the ineffectiveness of typical therapy and the patient’s severe clinical condition, she qualified for unconventional therapy (larval debridement therapy). Results: Larval wound debridement therapy and negative-pressure wound therapy were used for the tracheocutaneous fistula; this is the first case of this alternative therapy being described in the English-language literature. In this case, based on an analysis of the health benefits for the patient and the uncertain prognosis, larval therapy was used for a postoperative wound after strumectomy with the presence of a tracheocutaneous fistula, and negative-pressure wound therapy ultimately led to complete wound healing. Conclusions: Sepsis caused by Streptococcus pyogenes can be fulminant and often leads to complications or death, especially if it develops in the perioperative period. Larval therapy can be effectively used in cases of fistulas, such as tracheocutaneous fistulas, to prepare the wound bed for the next stage of healing using negative-pressure therapy, which ultimately leads to complete wound healing. Full article

Sepsis is a complex and heterogeneous condition, arising from a disrupted immune response to infection that can progress to organ failure and carries a high risk of death. In recent years, growing attention has been paid to the role of epigenetic mechanisms—including DNA methylation, histone modifications, non-coding RNAs, and RNA methylation—in shaping immune activity during sepsis. These processes affect immune functions such as macrophage polarization, cytokine release, and the exhaustion of immune cells, and they help explain the shift from an initial phase of overwhelming inflammation to a later state of immune suppression. Epigenetic alterations also contribute to tissue-specific damage, notably in the lungs, kidneys, and heart, and have been linked to disease severity and clinical prognosis. Advances in transcriptomic and epigenetic profiling have made it possible to distinguish molecular subtypes of septic patients, each with distinct immune features and varied responses to treatments such as corticosteroids and metabolic therapies. Emerging biomarkers—like AQP5 methylation, histone lactylation (H3K18la), and m⁶A RNA methylation—are opening new options for patient classification and more tailored therapeutic strategies. This review examines the current understanding of how epigenetic regulation contributes to the pathophysiology of sepsis and considers its implications for developing more individualized approaches to care. Full article

Sepsis is a complex and life-threatening syndrome arising from a dysregulated immune response to infection that can lead to severe organ dysfunction and increased mortality. This multifactorial condition is marked by intricate interactions between immune, inflammatory, and coagulation pathways, which together contribute to systemic effects and multiorgan damage. The aberrant immune activation seen in sepsis includes profound leukocyte activation, endothelial dysfunction, imbalanced coagulation leading to disseminated intravascular coagulation (DIC), and the production of both pro-inflammatory and anti-inflammatory mediators. These events culminate in pathological alterations that extend beyond the initial site of infection, adversely impacting distant tissues and organs. Early recognition and timely intervention are crucial to mitigate the progression of sepsis and its associated complications. This review aims to explore the underlying biological mechanisms, including host–pathogen interactions, immune dysregulation, and the cascade of systemic and organ-specific effects that define sepsis. By delving into the pathophysiological processes, we intend to provide insights into the determinants of multiorgan failure and inform strategies for therapeutic intervention. Understanding these mechanisms is pivotal for advancing clinical outcomes and reducing mortality rates associated with this critical condition. Full article

Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article

Background: COVID-19-associated coagulopathy (CAC) is a complex condition, with high rates of thrombosis, high levels of inflammation markers and hypercoagulation (increased levels of fibrinogen and D-Dimer), as well as extensive microthrombosis in the lungs and other organs of the deceased. It resembles, without being identical, other coagulation disorders such as sepsis-DIC (SIC/DIC), hemophagocyte syndrome (HPS) and thrombotic microangiopathy (TMA). Platelets (PLTs), key regulators of thrombosis, inflammation and immunity, are considered an important risk mediator in COVID-19 pathogenesis. Platelet index MPV/PLT ratio is reported in the literature as more specific in the prognosis of platelet-related systemic thrombogenicity. Studies of MPV/PLT ratio with regards to the severity of COVID-19 disease are limited, and there are no references regarding this ratio to the outcome of COVID-19 disease at specific time points of hospitalization. The aim of this study is to evaluate the relationship of COVID-19 mortality with the red cell distribution width–coefficient of variation (RDW-CV), platelets and MPV/PLT ratio parameters. Methods: Values of these parameters in 511 COVID-19 hospitalized patients were recorded (a) on admission, (b) as mean values of the 1st and 2nd week of hospitalization, (c) over the total duration of hospitalization, (d) as nadir and zenith values, and (e) at discharge. Results: As for mortality (survivors vs. deceased), statistical analysis with ROC curves showed that regarding the values of the parameters on admission, only the RDW-CV baseline was of prognostic value. Platelet parameters, absolute number and MPV/PLT ratio had predictive potential for the disease outcome only as 2nd week values. On the contrary, with regards to disease severity (mild/moderate versus severe/critical), only the MPV/PLT ratio on admission can be used for prognosis, and to a moderate degree. On multivariable logistic regression analysis, only the RDW-CV mean hospitalization value (RDW-CV mean) was an independent and prognostic variable for mortality. Regarding disease severity, the MPV/PLT ratio on admission and RDW-CV mean were independent and prognostic variables. Conclusions: RDW-CV, platelets and MPV/PLT ratio hematological parameters could be of predictive value for mortality and severity in COVID-19 disease, depending on the hospitalization timeline. Full article

In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10⁸ M⁻¹. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. Full article