Persistent Inflammatory Response Research Articles

Pyroptosis in asthma: inflammatory phenotypes, immune and non-immune cells, and novel treatment approaches

Pyroptosis is a form of inflammatory programmed cell death, and is activated by pathogen infections or endogenous danger signals. The canonical pyroptosis process is characterized by the inflammasome (typically NLRP3)-mediated activation of caspase-1, which in turn cleaves and activates IL-1β and IL-18, as well as gasdermin D, which is a pore-forming executor protein, leading to cell membrane rupture, and the release of proinflammatory cytokines and damage-associated molecular pattern molecules. Pyroptosis is considered a part of the innate immune response. A certain level of pyroptosis can help eliminate pathogenic microorganisms, but excessive pyroptosis can lead to persistent inflammatory responses, and cause tissue damage. In recent years, pyroptosis has emerged as a crucial contributor to the development of chronic inflammatory respiratory diseases, such as asthma. The present study reviews the involvement of pyroptosis in the development of asthma, in terms of its role in different inflammatory phenotypes of the disease, and its influence on various immune and non-immune cells in the airway. In addition, the potential therapeutic value of targeting pyroptosis for the treatment of specific phenotypes of asthma is discussed.

Thermoregulation and survival during sepsis: insights from the cecal ligation and puncture experimental model

BackgroundSepsis remains a major global health concern due to its high prevalence and mortality. Changes in body temperature (Tb), such as hypothermia or fever, are diagnostic indicators and play a crucial role in the pathophysiology of sepsis. This study aims to characterize the thermoregulatory mechanisms during sepsis using the cecal ligation and puncture (CLP) model and explore how sepsis severity and ambient temperature (Ta) influence Tb regulation and mortality. Rats were subjected to mild or severe sepsis by CLP while housed at thermoneutral (28 °C) or subthermoneutral (22 °C) Ta, and their Tb was monitored for 12 h. Blood and hypothalamus were collected for cytokines and prostaglandin E2 (PGE2) analysis.ResultsAt 28 °C, febrile response magnitude correlated with sepsis severity and inflammatory response, with tail vasoconstriction as the primary heat retention mechanism. At 22 °C, Tb was maintained during mild sepsis but dropped during severe sepsis, linked to reduced UCP1 expression in brown adipose tissue and less effective vasoconstriction. Despite differences in thermoregulatory responses, both Ta conditions induced a persistent inflammatory response and increased hypothalamic PGE2 production. Notably, mortality in severe sepsis was significantly higher at 28 °C (80%) compared to 22 °C (0%).ConclusionsOur findings reveal that ambient temperature and the inflammatory burden critically influence thermoregulation and survival during early sepsis. These results emphasize the importance of considering environmental factors in preclinical sepsis studies. Although rodents in experimental settings are often adapted to cold environments, these conditions may not fully translate to human sepsis, where cold adaptation is rare. Thus, researchers should carefully consider these variables when designing experiments and interpreting translational implications.Graphical Graphical representation of the thermoregulatory and inflammatory responses to mild and severe sepsis in rats housed at thermoneutral (28 °C) and subthermoneutral (22 °C) ambient temperatures (Ta). The model highlights distinct body temperature outcomes: fever and hypothermia. At thermoneutral Ta, severe sepsis induces a high fever, associated with increased hypothalamic PGE2, cytokine levels, and mortality, while mild sepsis leads to a moderate fever. In contrast, at subthermoneutral Ta, severe sepsis results in hypothermia with decreased UCP1 expression and lower mortality, whereas mild sepsis maintains normal body temperature. The impact of Ta on sepsis severity, thermoregulatory mechanisms, and survival is emphasized.

Chlorogenic Acid Alleviates Inflammation and Fibrosis in a Murine Model of Bleomycin-Induced Systemic Sclerosis: A Histological Analysis

Background/Objectives: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by cutaneous and visceral fibrosis, vascular alterations, and a persistent inflammatory response. Despite advances in understanding the pathogenic mechanisms underlying SSc, current therapeutic options remain limited. Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and has shown antioxidant, anti-inflammatory, and antifibrotic properties. However, its therapeutic potential in SSc has not been investigated yet. Methods: A model of SSc was established by administering bleomycin (BLM) at 100 U/kg to CD1 mice via an osmotic minipump. After fourteen days of BLM administration, CGA (60 mg/kg) was intragastric administered on consecutive days until day 20. On day 21, all mice were sacrificed. The effect of CGA was histologically evaluated by hematoxylin and eosin and Masson’s trichrome staining. Results: CGA treatment significantly attenuated dermal fibrosis in the BLM-induced mice model of SSc by reducing histopathological damage, including increased dermal thickness, inflammation, collagen deposition, and SSc-associated pulmonary fibrosis. Conclusions: The evidence shows that CGA attenuates BLM-induced SSc in a mice model and strongly suggests that CGA may be a promising compound for the treatment of SSc.

MiR-144/451: A Regulatory Role in Inflammation.

Inflammation is the natural defense mechanism of the body in response to injury, infection, or other stimuli. Excessive or persistent inflammatory responses can lead to the development of inflammatory diseases. Therefore, elucidating the regulatory mechanisms of inflammatory cells is crucial for understanding the pathogenesis of such diseases and devising novel therapeutic approaches. Moreover, miR-144/451 plays an important role in erythroid maturity and tumour development. Herein, we have reviewed the regulatory role of miR-144/451 in inflammation. Papers on miR-144, miR-451, and inflammation were retrieved from PubMed and Web of Science to be analysed and summarised. miR-144/451 plays a significant role in modulating inflammatory responses. Pro- and anti-inflammatory gene transcription is regulated by miR-144/451 binding to the 3' untranslated regions. Studies have shown that miR-451 inhibits the activation of various inflammatory cells, including macrophages, neutrophils, and T lymphocytes, thereby reducing the release of inflammatory mediators. However, miR-144 expression varies in different inflammatory diseases. miR-144 expression is downregulated in macrophages after induction by lipopolysaccharide, cysteine, or Mycobacterium tuberculosis, which promotes the secretion of inflammatory mediators; nonetheless, miR-144-3p overexpression in macrophages can aggravate atherosclerosis. Meanwhile, miR-144 overexpression prevents disruption of the lung endothelial cell barrier, whereas it exacerbates endothelial cell injury in Crohn's disease. miR-144/451 may serve as a potential target for the treatment of inflammatory diseases.

The immune landscape in apical periodontitis: From mechanism to therapy.

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.

Co-delivery of antimicrobial peptide and Prussian blue nanoparticles by chitosan/polyvinyl alcohol hydrogels

Altered skin integrity increases the chance of infection, and bacterial infections often lead to a persistent inflammatory response that prolongs healing time. Functional artificial hydrogels are receiving increasing attention as suitable wound dressing barrier. However, the antimicrobial effect of the new dressing still needs to be explored in depth. In this work, the antimicrobial peptide MSI-1 was covalently attached to chitosan-modified poly (vinyl alcohol) hydrogels mixed with Prussian blue nanoparticles (PBNPs) via a primary amine group coupled to a carboxyl group. The synthesized hydrogel has a long-lasting antimicrobial surface and is able to maintain its bactericidal effect on Staphylococcus aureus and Escherichia coli for 24 h. Due to the presence of PBNPs, the hydrogel was able to rise to 48.3 °C within 10 min under near infrared (NIR) light irradiation at a wavelength of 808 nm and maintain this mild temperature to avoid bacterial biofilms. The hydrogel showed >90 % survival in co-culture with cells for 3 d and did not damage major organs in animal experiments. Thus, the photothermal dual-mode antimicrobial hydrogel synthesized in this study increases the selectivity as a safe and efficient wound dressing for the treatment of infected skin defects.

Review of Excessive Cytosolic DNA and Its Role in AIM2 and cGAS-STING Mediated Psoriasis Development.

In psoriasis, keratinocytes are triggered by factors, such as infection or tissue damage, to release DNA, which thereby activates plasmacytoid dendritic cells and macrophages to induce inflammation, thickened epidermis, and parakeratosis. The recognition of double-stranded (ds)DNA facilitates the activation of cytoplasmic DNA sensors absent in melanoma 2 (AIM2) inflammasome assembly and cyclic guanosine monophosphate adenosine monophosphate (cGAMP) synthase (cGAS) - stimulator of interferon gene (STING) pathway, both of which play a pivotal role in mediating the inflammatory response and driving the progression of psoriasis. Additionally, secreted proinflammatory cytokines can stimulate further DNA release from keratinocytes. Notably, the activation of AIM2 and cGAS-STING signaling pathways also mediates programmed cell death, potentially enhancing DNA overproduction. As a result, excessive DNA can activate these pathways, amplifying persistent inflammatory responses that contribute to the maintenance of psoriasis. Several studies have validated that targeting DNA and its mediated activation of AIM2 and cGAS-STING offers promising therapeutic strategies for psoriasis. Here, we postulate a hypothesis that excessive cytosolic DNA can activate AIM2 and cGAS-STING, mediating inflammation and programmed cell death, ultimately fostering DNA accumulation and contributing to the development of psoriasis.

A Paintable Small-Molecule Hydrogel with Antimicrobial and ROS Scavenging Activities for Burn Wound Healing.

Delayed wound healing induced by bacterial infection and a persistent inflammatory response remains a great clinical challenge. Herein, we reported a paintable, anti-bacterial, and anti-inflammatory Nap-F3K-CA (Nap-Phe-Phe-Phe-Lys-Caffeic Acid) hydrogel for burn wound management based on caffeic acid (CA)-functionalized short peptides (Nap-Phe-Phe-Phe-Lys). Hydrogels are assembled by non-covalent interactions between gelators, and the incorporation of CA promotes the self-assembly of the hydrogel. After being applied to burn wounds, the hydrogel effectively adapted to irregular wound beds and maintained a moist protective environment at the wound. The Nap-F3K-CA hydrogel can scavenge ROS to relieve oxidative damage and downregulate proinflammatory levels. The Nap-F3K-CA hydrogel also displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria, which reduced the incidence of wound infections. Moreover, the hydrogel exhibited good biocompatibility and hemostatic function. In vivo experiments demonstrated that the Nap-F3K-CA hydrogel significantly accelerated the repair of the skin structure including promoting collagen deposition, vascular regeneration, and hair follicle formation. These findings proved the clinical application potential of the Nap-F3K-CA hydrogel as a promising burn wound dressing.

Sodium butyrate alleviates lipopolysaccharide-induced inflammation through JAK/STAT signalling in primary human corneal fibroblasts

BackgroundBacterial keratitis is a common cause of blindness. Antibiotic treatment leads to the rapid release of lipopolysaccharide (LPS), which can activate corneal fibroblasts and cause persistent and excessive inflammatory responses. The anti-inflammatory drugs currently used to treat keratitis have serious side effects. Therefore, the ability of sodium butyrate (NaB), which can suppress the production of proinflammatory cytokines and promote the production of anti-inflammatory cytokines, to ameliorate keratitis was assessed in the present study. MethodsThe effect of NaB on the viability of primary human corneal fibroblasts was assayed with a CCK-8 kit. Cell migration was assessed by an in vitro scratch assay. Cell phenotypes were assessed by Western blotting and immunofluorescence staining. An antibody array was used to measure the production of proinflammatory cytokines and chemokines. ResultsAt 0–1 mM, NaB had no significant effect on cell viability, promoted the expression of the keratocyte marker keratocan and inhibited the fibroblast marker vimentin. Inhibition of cell migration was observed in the wound healing assay. By targeting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, NaB decreased the levels of inflammation-related cytokines and chemokines whose expression was induced by LPS. ConclusionsNaB maintained the keratocyte phenotype, inhibited cell migration, and relieved LPS-induced inflammatory responses through the JAK/STAT signalling pathway.

The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging.

Mitochondria are central to cellular energy production, and their dysfunction is a major contributor to oxidative stress and chronic inflammation, pivotal factors in aging, and related diseases. With aging, mitochondrial efficiency declines, leading to an increase in ROS and persistent inflammatory responses. Therapeutic interventions targeting mitochondrial health show promise in mitigating these detrimental effects. Antioxidants such as MitoQ and MitoVitE, and supplements like coenzyme Q10 and NAD + precursors, have demonstrated potential in reducing oxidative stress. Additionally, gene therapy aimed at enhancing mitochondrial function, alongside lifestyle modifications such as regular exercise and caloric restriction can ameliorate age-related mitochondrial decline. Exercise not only boosts mitochondrial biogenesis but also improves mitophagy. Enhancing mitophagy is a key strategy to prevent the accumulation of dysfunctional mitochondria, which is crucial for cellular homeostasis and longevity. Pharmacological agents like sulforaphane, SS-31, and resveratrol indirectly promote mitochondrial biogenesis and improve cellular resistance to oxidative damage. The exploration of mitochondrial therapeutics, including emerging techniques like mitochondrial transplantation, offers significant avenues for extending health span and combating age-related diseases. However, translating these findings into clinical practice requires overcoming challenges in precisely targeting dysfunctional mitochondria and optimizing delivery mechanisms for therapeutic agents. Continued research is essential to refine these approaches and fully understand the interplay between mitochondrial dynamics and aging.

Is The Peri-Implantitis Involved With Brain Inflammation And May Contribute To Neurodegenerative Disorders?

Oral rehabilitation encompasses the restoration of oral function, addressing issues related to the teeth, gums, and other oral structures. Dental implants have become the gold standard for the replacement of single or multiple missing teeth, but in individuals with poor oral hygiene, the accumulation of dental plaque biofilm can trigger a local immune and inflammatory host response leading to peri-implant mucositis (a reversible condition with localized therapies) or peri-implantitis (characterized by bone loss accompanied by a persistent immune and inflammatory host response). The presence of periodontal pathogens at sites with peri-implantitis has been reported in several studies, and there is extensive documentation of similarities in microbial profiles between periodontitis sites and peri-implantitis sites. Thus, periodontitis/apical periodontitis can reach distant organs, especially the brain. This can lead to the development or exacerbation of inflammatory conditions. Similarly, the microorganisms and their products responsible for inducing peri-implantitis can potentially cause inflammatory conditions in the brain like periodontitis/apical periodontitis. Then, it is plausible to infer that peri-implantitis may be used the same way to induce and/or potentialize brain inflammation

In vitro and in vivo evaluation of the diabetic wound healing properties of Saffron (Crocus Sativus L.) petals

Wound healing is a complex process orchestrated by interactions between a variety of cell types, including keratinocytes, fibroblasts, endothelial cells, inflammatory cells, and bioactive factors such as extracellular matrix (ECM) components, growth factors, and cytokines. Chronic wounds exhibit delayed proliferative phase initiation, reduced angiogenesis, impaired ECM synthesis, and persistent inflammatory response. Chronic wounds are one of the main challenges to the healthcare system worldwide, with a high cost for medical services. Hence, investigation of new approaches to accelerate wound healing is essential. Phytomedicines are considered as potential agents for improving the wound healing by accelerating epithelization, collagen synthesis, and angiogenesis. These natural compounds have various advantages including availability, ease of application, and high effectiveness in wound managment. This study aimed to investigate the biological effects of saffron or Crocus sativus L. (C. sativus) petal extract on cell survival, migration, and angiogenesis using MTT, scratch and in vitro tube formation assays. Moreover, the expression of collagen type I alpha 1 (COL1A1) and vascular endothelial growth factor (VEGF) were evaluated in human dermal fibroblasts (HDF)s and human umbilical vein endothelial cells (HUVEC)s, respectively. The effect of the C. sativus extract on the skin of diabetic mice was also monitored. The results showed that C. sativus petal extract promoted the viability and migration of HDFs and HUVECs. Moreover, C. sativus petal extract enhanced the formation of tube-like structures by HUVECs cultured on the Matrigel basement membrane matrix, indicating its potential to stimulate angiogenesis. Gene expression studies have shown the the C. sativus extract increases wound healing by upregulation of COL1A1 and VEGF, which are crucial factors involved in collagen deposition, epithelialization, and angiogenesis. Histological analysis revealed that C. sativus petal extract enhanced vascularity and increased the number of fibroblasts and collagen synthesis, ultimately accelerating wound closure compared to wounds treated with eucerin and commercial ointment in diabetic mice. Therefore, C. sativus petal extract has potential as a herbal treatment to improve the healing of diabetic wounds.

A pentavalent peptide vaccine elicits Aβ and tau antibodies with prophylactic activity in an Alzheimer’s disease mouse model

Amyloid-β (Aβ) and hyperphosphorylated tau protein are targets for Alzheimer’s Disease (AD) immunotherapies, which are generally focused on single epitopes within Aβ or tau. However, due to the complexity of both Aβ and tau in AD pathogenesis, a multipronged approach simultaneously targeting multiple epitopes of both proteins could overcome limitations of monotherapies. Herein, we propose an active AD immunotherapy based on a nanoparticle vaccine comprising two Aβ peptides (1–14 and pyroglutamate pE3-14) and three tau peptides (centered on phosphorylated pT181, pT217 and pS396/404). These correspond to both soluble and aggregated targets and are displayed on the surface of immunogenic liposomes in an orientation that maintains reactivity with epitope-specific monoclonal antibodies. Intramuscular immunization of mice with individual epitopes resulted in minimally cross-reactive antibody induction, while simultaneous co-display of 5 antigens (“5-plex”) induced antibodies against all epitopes without immune interference. Post-immune sera recognized plaques and neurofibrillary tangles from human AD brain tissue. Vaccine administration to 3xTg-AD mice using a prophylactic dosing schedule inhibited tau and amyloid pathologies and resulted in improved cognitive function. Immunization was well tolerated and did not induce antigen-specific cellular responses or persistent inflammatory responses in the peripheral or central nervous system. Antibody levels could be reversed by halting monthly vaccinations. Altogether, these results indicate that active immune therapies based on nanoparticle formulations of multiple Aβ and tau epitopes warrant further study for treating early-stage AD.

A chitosan-based light-curing hydrogel dressing for accelerated healing of infected wounds

Bacterial infections, excessive reactive oxygen species (ROS) accumulation and a persistent inflammatory response severely impede the wound healing process. In this study, we developed a novel multifunctional hydrogel dressing (LCPN) based on lipoic acid modified chitosan (LAMC), polypyrrole nanoparticles (PPy NPs) and nicotinamide mononucleotide (NMN) for accelerated healing of infected wounds. The synthesized LCPN hydrogel has several properties. Modification of lipoic acid significantly enhances the water solubility of chitosan making it easier to dissolve and absorb wound secretions. Interestingly, owing to the breaking and restructuring of disulfide bonds, LCPN hydrogel can be quickly bonded under UV light without relying on photoinitiators. In addition, the incorporation of PPy NPs not only enhances the electrical conductivity of LCPN hydrogel, but also confers photothermal antimicrobial capability to LCPN hydrogel. More importantly, the sustained release of NMN in LCPN hydrogel can significantly enhance cell proliferation, migration and antioxidant capacity, which is conducive to accelerated wound healing. In vitro and in vivo experiments have shown that LCPN hydrogel has excellent biocompatibility and the ability to promote wound healing. Therefore, the prepared multifunctional hydrogel is expected to be used as a novel dressing to accelerate wound healing.

Increased levels of regulatory T cells and IL-10-producing regulatory B cells are linked to improved clinical outcome in Parkinson's disease: a 1-year observational study.

Whilst the contribution of peripheral and central inflammation to neurodegeneration in Parkinson's disease and the role of the immune response in this disorder are well known, the effects of the anti-inflammatory response on the disease have not been described in depth. This study is aimed to assess the changes in the regulatory/inflammatory immune response in recently diagnosed, untreated PD patients and a year after. Twenty-one PD patients and 19 healthy controls were included and followed-up for 1 year. The levels of immunoregulatory cells (CD4+ Tregs, Bregs, and CD8+ Tregs); classical, nonclassical, and intermediate monocytes, and proinflammatory cells (Th1, Th2, and Th17) were measured by flow cytometry. Cytokine levels were determined by ELISA. Clinical follow-up was based on the Hoehn & Yahr and UDPRS scales. Our results indicate that the regulatory response in PD patients on follow-up was characterized by increased levels of active Tregs, functional Tregs, TR1, IL-10-producing functional Bregs, and IL-10-producing classical monocytes, along with decreased counts of Bregs and plasma cells. With respect to the proinflammatory immune response, peripheral levels of Th1 IFN-γ+ cells were decreased in treated PD patients, whilst the levels of CD4+ TBET+ cells, HLA-DR+ intermediate monocytes, IL-6, and IL-4 were increased after a 1-year follow-up. Our main finding was an increased regulatory T cell response after a 1-year follow-up and its link with clinical improvement in PD patients. In conclusion, aftera 1-year follow-up, PD patients exhibited increased levels of regulatory populations, which correlated with clinical improvement. However, a persistent inflammatory environment and active immune response were observed.

Multifunctional Bioactive Nanozyme Systems for Enhanced Diabetic Wound Healing.

The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO₂-Au-mSiO₂@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO₂ head and MnO₂ extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO₂-Au-mSiO₂@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS-scavenging and growth factor-releasing system, is developed. The HAMA-mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti-inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.

Odontogenic Maxillary Sinusitis: A clinical case report

underdiagnosed due to its nonspecific clinical presentation, which overlaps with other types of rhinosinusitis. The etiopathogenesis involves a complex interplay of factors including iatrogenic causes, periodontal infections, and traumatic events, leading to a persistent inflammatory response in the maxillary sinus. This report details a clinical case involving a 19-year-old male patient presenting with exacerbated sinusitis symptoms linked to a carious upper right first molar. Clinical manifestations included blurred vision, facial pain, and nasal regurgitation of liquids. Radiographic analysis revealed a radiolucent area indicative of sinus involvement, confirming the diagnosis of OMS.Surgical intervention comprised the extraction of the infected molar and the debridement of the maxillary sinus, followed by the application of Bichat’s fat pad to repair the resulting oroantral communication. This technique demonstrated effective closure of the defect, promoting tissue healing and reducing postoperative complications. The postoperative regimen included antibiotics, anti-inflammatories, and antihistamines, which facilitated recovery. This case underscores the necessity of a multidisciplinary approach in the diagnosis and management of OMS, integrating dental and surgical expertise to optimize patient outcomes. Imaging plays a crucial role in the diagnostic process, enabling precise identification of odontogenic lesions and their extent. The successful use of Bichat’s fat pad highlights its utility in oral-maxillofacial surgery for managing oroantral fistulas. This report contributes to the growing body of evidence supporting the importance of tailored surgical and medical strategies in managing complex cases of odontogenic maxillary sinusitis.

Variability of changes in proand antiinflammatory cytokines due to IFNα and IFNγ deficiency in patients with post-covid syndrome associated with activation of chronic herpes viral infections

Post-COVID syndrome (PCS) is characterized by long-term complications and conditions accompanied by neuroimmunoinflammation, and includes chronic fatigue syndrome (CFS) and cognitive disorders (CD), which are often associated with activation of chronic herpesvirus infections (HVI). Timely detection of symptoms and immunodiagnosis of PCS are a priority and are of undoubted interest. Objective: to clarify the levels of serum proand anti-inflammatory cytokines, alpha and gamma interferons in patients with post-COVID syndrome associated with confirmed activation of chronic herpesvirus infections. Patients (n = 60) aged from 18 to 65 years with complaints of manifestations of PCS associated with HVI were studied — the study group (SG). A survey was conducted using a modified scale-questionnaire to assess the severity of PCS symptoms in points from 0 to 4, real-time PCR of HVI (EBV, HSV1/2, VCH6, VCH8, CMV) in saliva and scrapings from the tonsils, determination of the level of IFNα and IFNγ, pro- (TNFα, IL-18, IL-1β, IL-6, IL-17A, IL-8) and anti-inflammatory (IL-4 and IL-10) cytokines in blood serum. Comparison group (CG) — 60 apparently healthy individuals. SG patients with mixed HVI with EBV dominance noted the most pronounced and persistent clinical manifestations of PCS, among which the leading place was occupied by longterm sensations of CFS and CD. A persistent multisystem inflammatory response was identified, confirmed by elevated levels of IL-6 and IL-17A, which caused severe PCS. In post-COVID period, hyperproduction of IL-1β was detected, which was accompanied by clinical manifestations of persistent neuroimmunoinflammation. At the same time, the identified deficiency of IFNα, IFNγ and dysregulatory disorders in the antiviral defense of the immune system in patients with PCS contributed to the activation of HVI. Data on the imbalance of proand anti-inflammatory cytokines in the SG were obtained, which confirms the presence of a persistent multisystem inflammatory reaction with dominance of persistent neuroimmunoinflammation, which causes severe PCS. An imbalance of the cytokine system with IFNα and IFNγ deficiency, associated with the activation of chronic HVI with EBV dominance in the post-COVID period, contributes to the development of neuroimmunoinflammation, which is accompanied by the leading clinical signs of PCS: CFS and CD.

Is serum albumin a pivotal biomarker in anticipating acute pancreatitis outcomes?

This study aimed to assess the significance of serum albumin levels within 24 h of patient admission in correlation with the incidence of outcomes and mortality in patients diagnosed with acute pancreatitis. A retrospective study was conducted over a 5-year period, from January 2018 to December 2023, at the Mohammed VI University Hospital in Oujda, Morocco. The study included 371 patients diagnosed with acute pancreatitis. Hypoalbuminemia (≤ 30 g/L) was observed in 124 patients (33.4% of cases), and these patients had a higher mean age compared to those with normal albumin levels (P = 0.003). Hypoalbuminemia was significantly associated with persistent Systemic Inflammatory Response Syndrome (SIRS) (70.8% vs. 29.2%, P = 0.000), a higher BISAP score (66.7% vs. 33.3%, P = 0.000), and a higher CTSI score (51.7% vs. 48.3%, P = 0.000). Hypoalbuminemia was also associated with the presence of pleural effusion (P = 0.000). The mortality in the sample was 4.6%, and it was significantly associated with hypoalbuminemia (76.5%, P = 0.000). In conclusion, serum albumin levels within 24 h of patient admission appear to be a significant prognostic biomarker in acute pancreatitis, particularly in anticipating persistent organ failure and mortality.

Sub-Chronic Methomyl Exposure Induces Oxidative Stress and Inflammatory Responses in Zebrafish with Higher Female Susceptibility.

The widespread use of carbamate pesticides has raised significant environmental and health concerns, particularly regarding water contamination and the disruption of defense systems in organisms. Despite these concerns, research on the differential impacts of pesticides on male and female organisms remains limited. This study focused on methomyl, investigating sex-specific differences in liver antioxidant defenses and inflammatory response indices in male and female zebrafish after 56 days of exposure to environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings indicate that methomyl exposure significantly increased ROS content in zebrafish livers, inducing oxidative stress and activating enzymatic antioxidant defenses such as SOD, CAT, and GSH-Px activities. Sub-chronic exposure altered the expression of apoptosis-related genes (Bax/Bcl2a and Caspases3a), resulting in liver cell apoptosis in a concentration-dependent manner, with the 0.20 mg/L concentration causing the most severe damage. Additionally, methomyl exposure at environmentally relevant concentrations triggered persistent inflammatory responses in liver tissues, evidenced by increased transcription levels of inflammatory factor genes and the activation of toll-like receptors, heightening susceptibility to exogenous allergens. It is noteworthy that oxidative damage indicators (AST, ROS, MDA) and inflammatory gene expressions (IL-1β, TNF-α) were significantly higher in female livers compared to male livers at 0.10-0.20 mg/L methomyl exposure. Consequently, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms and highlights the need for heightened consideration of the risks posed by environmental endocrine disruptors to female health and safety.