Inflammation Research Articles

Fundamentals of intervertebral disc degeneration and related discogenic pain

Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain, although the mechanisms by which it occurs and leads to pain remain unclear. In healthy adult discs, vessels and nerves are present only in the outer layer of the annulus fibrosus and in the bony endplate. Animal models, and histological and biomechanical studies have shown that annulus tear or endplate injury is the initiating factor for painful disc degeneration. Injury to the disc triggers a local inflammatory repair response that activates nociceptors and promotes the synthesis of neuropeptides such as substance P and calcitonin gene-related peptide, by dorsal root ganglion neurons. These neuropeptides are transported to injured discs and act as pro-inflammatory molecules, promoting the production of an “inflammatory soup” by inducing vasodilatation and plasma extravasation as well as by promoting the release of chemical mediators from disc cells and infiltrating immune cells, causing neurogenic inflammation that leads to progressive disc degeneration and discogenic pain.

Autophagy serves as a protective effect against inflammatory injury of oxidative stress in ARPE-19 cell

AIM: To test the effect of autophagy on inflammatory damage resulting from oxidative stress in adult retinal pigment epithelial cell line (ARPE-19). METHODS: ARPE-19 cells were pretreated with 200 and 600 µmol/L hydrogen peroxide (H2O2) at various time intervals. The changes of cell morphology, cell viability, reactive oxygen species (ROS) level, autophagic activity, and the inflammatory cytokines (TNFα, IL-6, and TGFβ) were measured at baseline and after treatment with autophagy inducer rapamycin (Rapa) and suppressor wortmannin (Wort) or shATG5. RESULTS: The levels of ROS, cytokines (TNFα, IL-6, and TGFβ), and autophagic activity were significantly increased in ARPE-19 cells after pretreated with H2O2 (all P<0.05) and IL-10 was significantly decreased (P<0.05). By upregulating autophagy, Rapa significantly reduced oxidative stress-induced secretion of pro-inflammatory factors (TNFα and IL-6) and ROS (all P<0.05), yet elevated the production of TGFβ (P<0.05). In contrast, suppression of autophagy through Wort or ATG5 knockdown reduced cell viability, increased cell apoptotic rate, and exacerbated the generation of ROS and inflammatory cytokines (TNFα, IL-6, and TGFβ; all P<0.05). CONCLUSION: Autophagy demonstrates a protective effect on ARPE-19 cell through mitigating oxidative damage and oxidative stress-induced inflammatory response. Regulation of autophagy may be a potential way for age-related macular degeneration.

Role of neurogenic inflammation in intervertebral disc degeneration

In healthy intervertebral discs (IVDs), nerves and blood vessels are present only in the outer annulus fibrosus, while in degenerative IVDs, a large amount of nerve and blood vessel tissue grows inward. Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration. Recently, non-neuronal cells, including IVD cells and infiltrating immune cells, have emerged as important players in neurogenic inflammation. IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system. In return, IVD cells and immune cells produce neuropeptides and nerve growth factor, which stimulate nerve fibers. This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD. Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs. These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs. Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain.

Fractional exhaled nitric oxide and respiratory symptoms in central sterile supply department workers exposed to different ventilation systems

ABSTRACT Objective: To verify the association between different types of ambient ventilation in Central Sterile Supply Department (CSSD), fractional exhaled nitric oxide (FeNO) values, and respiratory symptoms of workers . Methods: CSSD workers from five hospitals were evaluated in three different ventilation systems: negative air pressure, air conditioning, and natural ventilation. The prevalence of respiratory symptoms was evaluated by The European Community Respiratory Health Survey. The respiratory inflammatory response was evaluated utilizing FeNO level measurements. Results: There was a general prevalence of respiratory symptoms in 5% of the workers investigated; there was no association between respiratory symptoms and ventilation systems (p = 0.170). Of the total workers investigated, 22% had FeNO levels ≥ 25 parts per billion (ppb), considered above the normal range, and there was a statistically significant difference between ventilation systems (p = 0.009) favoring natural ventilation. Conclusion: Exposure to the natural ventilation system reduced the chance of developing FeNO levels ≥ 25 by 94.3%.

Aminopeptidase N‐Activated Self‐immolative Hydrogen Sulfide Donor for Inflammatory Response‐Specific Wound Healing

Hydrogen sulfide (H2S) plays crucial inflammatory modulating roles, representing a promising candidate for anti‐inflammatory therapies. However, current H2S delivery approaches lack sufficient specificity against inflammatory response. Herein, regarding the overexpressed aminopeptidase N (APN) at the inflammation sites, an APN‐activated self‐immolative carbonyl sulfide (COS)/H2S donor (AlaCOS) was developed for inflammatory response‐specific H2S delivery. The compound showed sustained H2S generation upon APN activation in the presence of carbonic anhydrase (CA), and the responsiveness could be well regulated by modulating the amino acid sequence. Due to the inflammatory response‐specific sustained H2S delivery, AlaCOS provided potent anti‐inflammatory capability, which was further validated by RNA sequencing. In vivo experiments on a full‐thickness cutaneous wound murine model also showed the strong promoting effect on wound healing, mainly due to the regulation of the inflammatory response by AlaCOS. By introducing a caged coumarin fluorophore to the molecular architecture, self‐reporting fluorescence could be generated accompanied with APN‐mediated COS/H2S release, which achieved the visualization of H2S delivery in vitro and in vivo. This work not only offers a useful tool for studying the bioactivity of H2S on inflammation, but also provides new insights for developing novel therapies to cope with inflammation‐associated diseases.

Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration

Abstract Cellular senescence contributes to inflammation and organ dysfunction during aging. While this process is generally characterized by irreversible cell cycle arrest, its morphological features and functional impacts vary in different cells from various organs. In this study, we examined the expression of multiple senescent markers in the lungs of young and aged humans and mice, as well as in mouse lung endothelial cells cultured with a senescence inducer, suberoylanilide hydroxamic acid (SAHA), or doxorubicin (DOXO). We detected increased levels of p21, γH2AX, and SA-β-Gal and decreased Ki-67 and Lamin B1 in aged lungs and senescent lung endothelial cells. Importantly, the expression of senescent markers was associated with an inflammatory response in aged mouse lungs characterized by neutrophil infiltration, increased expression of intercellular adhesion molecule 1 (ICAM-1), and decreased protein levels of VE-cadherin and ZO-1. As the latter two are critical constituents of endothelial cell–cell junctions, we hypothesized that their decreased expression could lead to compromised junction barrier integrity. Indeed, senescent endothelial cells (ECs) exhibited impaired barrier properties, as measured by increased permeability to solutes of small size (3-kD) and albumin (70-kD). When co-cultured with neutrophils, senescent ECs and their supernatant promoted neutrophil chemotaxis and trans-endothelial migration. Taken together, our results suggest that lung EC senescence weakens cell–cell junctions, impairs barrier function, and promotes neutrophil adhesion and migration, which may contribute to the development of inflammation and related pathologies in the lungs during aging.

Aminopeptidase N‐Activated Self‐immolative Hydrogen Sulfide Donor for Inflammatory Response‐Specific Wound Healing

Hydrogen sulfide (H2S) plays crucial inflammatory modulating roles, representing a promising candidate for anti‐inflammatory therapies. However, current H2S delivery approaches lack sufficient specificity against inflammatory response. Herein, regarding the overexpressed aminopeptidase N (APN) at the inflammation sites, an APN‐activated self‐immolative carbonyl sulfide (COS)/H2S donor (AlaCOS) was developed for inflammatory response‐specific H2S delivery. The compound showed sustained H2S generation upon APN activation in the presence of carbonic anhydrase (CA), and the responsiveness could be well regulated by modulating the amino acid sequence. Due to the inflammatory response‐specific sustained H2S delivery, AlaCOS provided potent anti‐inflammatory capability, which was further validated by RNA sequencing. In vivo experiments on a full‐thickness cutaneous wound murine model also showed the strong promoting effect on wound healing, mainly due to the regulation of the inflammatory response by AlaCOS. By introducing a caged coumarin fluorophore to the molecular architecture, self‐reporting fluorescence could be generated accompanied with APN‐mediated COS/H2S release, which achieved the visualization of H2S delivery in vitro and in vivo. This work not only offers a useful tool for studying the bioactivity of H2S on inflammation, but also provides new insights for developing novel therapies to cope with inflammation‐associated diseases.

L-selectin Promotes Migration, Invasion and Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via NF-kB Signaling Pathway

L-selectin Promotes Migration, Invasion and Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via NF-kB Signaling Pathway

Immune-Boosting and Antiviral Effects of Antioxidants in COVID-19 Pneumonia: A Therapeutic Perspective

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has profoundly impacted global health, with pneumonia emerging as a major complication in severe cases. The pathogenesis of COVID-19 is marked by the overproduction of reactive oxygen species (ROS) and an excessive inflammatory response, resulting in oxidative stress and significant tissue damage, particularly in the respiratory system. Antioxidants have garnered considerable attention for their potential role in managing COVID-19 pneumonia by mitigating oxidative stress and modulating immune responses. This review provides a comprehensive overview of the literature on the use of antioxidants in hospitalized patients with mild-to-moderate COVID-19. Studies exploring antioxidants, including vitamins, trace elements, nitric oxide (NO), ozone (O3), glutathione (GSH), L-carnitine, melatonin, bromelain, N-acetylcysteine (NAC), and numerous polyphenols, have yielded promising outcomes. Through their ROS-scavenging properties, these molecules support endothelial function, reduce the thrombosis risk, and may help mitigate the effects of the cytokine storm, a key contributor to COVID-19 morbidity and mortality. Clinical evidence suggests that antioxidant supplementation may improve patient outcomes by decreasing inflammation, supporting immune cell function, and potentially shortening recovery times. Furthermore, these molecules may mitigate the symptoms of COVID-19 by exerting direct antiviral effects that inhibit the infection process and genomic replication of SARS-CoV-2 in host cells. Moreover, antioxidants may work synergistically with standard antiviral treatments to reduce viral-induced oxidative damage. By integrating findings from the literature with real-world data from our clinical experience, we gain a more profound understanding of the role of antioxidants in managing COVID-19 pneumonia. Further research combining comprehensive literature reviews with real-world data analysis is crucial to validate the efficacy of antioxidants and establish evidence-based guidelines for their use in clinical practice.

Paravertebral crystal deposition disease: a retrospective study of clinical presentation, prevalence, and CT imaging findings

Abstract Objectives Paravertebral crystal deposition disease, characterized by the deposition of crystals around the vertebral bodies leading to acute inflammation and pain, is a condition that remains largely unrecognized. This study aims to elucidate the prevalence, clinical features, and CT findings associated with this disease. Methods We retrospectively analyzed 14,839 consecutive patients who underwent chest and/or abdominal CT (September 2017 to September 2024) owing to chest, abdominal, or back pain. Cases demonstrating paravertebral calcification with a surrounding soft tissue density of ≥ 5 mm were identified and further evaluated. Results Twenty-four cases of paravertebral crystal deposition disease were identified, with a prevalence of 0.16% (95% CI: 0.10, 0.24). The mean age was 46.2 years, with a female predominance (n = 15, 63%). Back pain was the most common presenting symptom (n = 15, 63%). Calcifications were primarily located at the lower thoracic and upper lumbar spine (Th6/7-L1/2) in 18 cases (75%) and in the anterior median to anterior right region of the vertebral body in 21 cases (86%). Mean of maximum CT values of the crystal deposition was approximately 800 HU; in follow-up cases, the depositions either resolved or exhibited morphological changes. Conclusions This study adds to the current knowledge base by identifying a 0.16% prevalence of paravertebral crystal deposition disease in patients with torso pain—often overlooked in clinical practice, primarily affecting middle-aged women. CT imaging shows calcifications mainly in the lower thoracic and upper lumbar spine. Considering this self-limiting disease in differential diagnoses can improve diagnostic accuracy and patient management.

The measurement of microplastics in surface water and their impact on histopathological structures in wading birds of district Lahore

Plastics are globally considered a significant threat, particularly to metropolitan areas, due to the extensive use of plastic products. This research is the first of its kind to document microplastics contamination and its effects on Red wettled lapwing (Vanellus indicus). The concentration of microplastics (MPs) was measured from surface water at different locations including canals and drains, which are the primary sources of MPs pollution in the metropolitan city Lahore, Pakistan. The highest MPs concentration was recorded in the main stream of the Ravi River, with an average concentration of 5,150 ± 7.5 particles/m3. In addition, considering the different shapes of MPs, fibers were found to be most abundant at Site I (Main Stream of River Ravi), with the highest mean concentration of 92.4 ± 0.3 particles/m3, whereas the lowest mean concentration of 29.9 ± 0.1 particles/m3 was observed. In contrast, fragments were predominant at Site II (Shahdara Drain), with the highest and lowest mean concentrations of 42.6 ± 0.3 and 21.7 ± 0.1particles/m3, respectively. Chemical analysis revealed that most fragments, fibers; and beads belonged to the polyethylene class, while sheets were categorized as polypropylene and foam as polystyrene. The large MPs with particle size ranging from 400 μm to 5 mm were most abundant at both locations. Particles smaller than 0.5 mm were the most prevalent (56%) at Site I, while Site II showed the lowest proportions for size ranges 0.5–1 mm (24%), 1–2 mm (16%), 2–3 mm (8%), 3–4 mm (5%), and 4–5 mm (3%). The frequency of occurrence (%FO; prevalence) of plastics in necropsied birds was 89.7%. A total of 120 items were analyzed: 64 fibers, 23 fragments, 10 pieces of foam, 14 pieces of sheet, and 9 beads. Of the total ingested plastic debris analyzed, the largest proportion was comprised of polyethylene, making up 46% of the samples. Birds from Site I (Main Stream of River Ravi) had 100% of their organs containing plastic items compared to those from Site II (Shahdara Drain). Quantitative and qualitative histopathological analyses were performed to examine variations in prevalence percentage, frequency, and histological alteration indices (HAI) as a consequence of MPs exposure on the health of wild species. Tissue samples from the liver and kidneys of the Red-wattled lapwing were analyzed, and comparisons were made to assess the extent of damage and degree of alteration in bird organs. The study evaluated the impacts of ingested MPs, which induced inflammatory and anatomical responses in V. indicus. Significant tissue damage was observed, including considerable inflammatory responses, evident cellular swelling in many renal tubular epithelial cells, and pyknotic nuclei, which were major causes of necrosis and apoptosis. Prevalence percentage and frequency were significantly higher at Site I compared to Site II. The highest prevalence percentages in the liver and kidneys were 90% and 85%, respectively, manifesting as degeneration of hepatocytes and necrosis in renal tubular epithelial cells in response to 0.5–1 mm sized MPs. The lowest prevalence percentage, 5%, was observed as congestion of sinusoids and hyperemia in response to 4–5 mm sized MPs. The frequency and prevalence percentages followed the order: 0.5 mm > 0.5–1 mm > 1–2 mm > 2–3 mm > 3–4 mm > 4–5 mm > 0 mm (0 mm as control).This investigation contributes to the growing documentation of MPs abundance in freshwater ecosystems and provides a baseline for future studies on MPs pollution in the Ravi River.

Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS

IntroductionThe severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between disrupted sympathetic regulation and splenocyte apoptosis in high thoracic SCI, leading to pulmonary dysfunction. The aim of this study was to investigate whether mice with low-level SCI exhibit increased susceptibility to acute lung injury by eliciting systemic inflammatory responses that operate independently of the sympathetic nervous system. MethodsHere, we employed T9 contusion SCI and exposed mice to aerosolized lipopolysaccharide (LPS) to simulate lung inflammation associated with acute respiratory distress syndrome (ARDS). Twenty-four hours post-LPS exposure, lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed. ResultsLPS markedly induced proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in SCI mice compared to controls, indicating an exaggerated inflammatory response. Infiltration of Ly6G/C positive neutrophils and macrophages was significantly higher in SCI mice lungs post-LPS exposure. Interestingly, spleen size and weight did not differ between control and SCI mice, suggesting that T9 SCI alone does not cause spleen atrophy. Notably, bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS. DiscussionsThis study demonstrated an increase in lung inflammation and immune responses subsequent to low-level T9 SCI, underscoring the widespread influence of systemic inflammation post-SCI, especially pronounced in specific organs like the lungs.

Tangeretin alleviates sepsis-induced acute lung injury by inhibiting ferroptosis of macrophage via Nrf2 signaling pathway

BackgroundSepsis-induced acute lung injury (ALI) is a severe clinical condition accompanied with high mortality. Tangeretin, which is widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether tangeretin protects against sepsis-induced ALI and the potential mechanisms remain unclear.MethodsWe established an ALI model via intraperitoneally injected with 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied intraperitoneally 30 min before LPS treatment. Dexamethasone (Dex) was used as a positive control. Hematoxylin and eosin (HE) staining and protein content in bronchoalveolar lavage fluid (BALF) were determined to detect the degree of lung injury. RNA-seq was also applied to explore the effect of tangeretin on ALI. In vitro, RAW264.7 were treated with Nrf2 siRNA, the expression of ferroptosis-associated biomarkers, including glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) were assessed. Glutathione (GSH), malondialdehyde (MDA) levels, reactive oxygen species (ROS) and inflammatory factors were also determined both in vivo and in vitro. Furthermore, mice were treated with an Nrf2 inhibitor (ML385) to verify the mechanism of tangeretin in inhibiting sepsis-induced lung injury and ferroptosis. Data were analyzed using one way analysis of variance or two-tailed unpaired t tests.ResultsOur study demonstrated that tangeretin significantly alleviated lung injury, reversed the LPS-induced reduction in GPX4 and GSH, and mitigates the elevation of PTGS2 and MDA levels. Tangeretin also reduced 4-HNE and iron levels. Besides, the levels of LPS-stimulated inflammatory factors IL-6, IL-1β and TNF-α were also decreased by tangeretin. RNA-seq and bioinformatics analysis demonstrated that tangeretin inhibited inflammatory response. Mechanistically, we identified that tangeretin inhibited the GPX4-dependent lipid peroxidation through activation of Nrf2. The silence of Nrf2 abolished the inhibitory effect of tangeretin on oxidative stress, inflammatory response and ferroptosis in RAW264.7 cells. Additionally, all the protective effects of tangeretin on ALI were abolished in Nrf2 inhibitor-treated mice.ConclusionWe identified that ferroptosis as a critical mechanism contributing to sepsis-induced ALI. Tangeretin, a promising therapeutic candidate, effectively mitigates ALI through inhibiting ferroptosis via upregulating Nrf2 signaling pathway.

Mutated IL-32θ (A94V) inhibits COX2, GM-CSF and CYP1A1 through AhR/ARNT and MAPKs/NF-κB/AP-1 in keratinocytes exposed to PM10

Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter’s (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses. This study revealed that one-point mutated IL-32θ (A94V) plays an important role in attenuating skin inflammation. IL-32θ (A94V) inhibited PM-induced COX-2, a pro-inflammatory cytokine GM-CSF and CYP1A1 in PM-exposed human keratinocytes HaCaT cells. IL-32θ (A94V) modulating effects were mediated via down-regulating ERK/p38/NF-κB/ AP-1 and AhR/ARNT signaling pathways. Our study indicates that PM triggers skin inflammation by upregulating COX-2, GM-CSF and CYP1A1 expression. IL-32θ (A94V) suppresses the expressions of COX-2, GM-CSF, and CYP1A1 by blocking the nuclear translocation of NF-κB and AP-1, as well as inhibiting the activation of the AhR/ARNT signaling pathway. Our findings offer valuable insights into developing therapeutic strategies and potential drugs to mitigate PM-induced skin inflammation by inhibiting the ERK/p38/NF-κB/AP-1 and AhR/ARNT signaling pathways.

Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation.

This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.

Changes and Long-Term Effects of the Immune System after COVID-19 Infection

Following the pandemic in 2020, physical health has generally declined. All of this is brought on by modifications to the body's immune system and the consequences of sequelae. The current research gap is caused by the neglect of COVID-19's after effects. In this paper, the relationship between immune system changes, complications and their physical conditions was studied, and preliminary results on the harm and prevention of the sequelae were obtained. The immune system's alterations during the epidemic infection and its consequences are the main topics of this article, including cytokine storms, inflammatory responses, and changes in immune cells. At the same time, the article explores the relationship between complications and underlying health conditions, such as chronic diseases and autoimmune diseases, and the harm they cause. Through observation and analysis in the later stages of the epidemic, the article explores the reasons for the general decline in people's physical fitness and changes in the immune system. In the future, it is hoped that there will be improvements in disease analysis and prevention measures after pandemic diseases.

Can we diagnose noninvasive follicular thyroid neoplasm with papillary-like nuclear features before surgery?

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) can be differentiated from invasive encapsulated follicular variant of papillary thyroid carcinoma (eFV-PTC) by the presence of a tumor capsule or blood vessel invasion in histological examination. The objective of this study was to investigate whether it is possible to distinguish between NIFTP and invasive eFV-PTC before surgery. Patients diagnosed with NIFTP and invasive eFV-PTC from 2017 to 2023 were analyzed for biochemical, ultrasonographic, and cytological features. No differences were found in thyroid function tests, thyroid autoantibody levels, tumor size, or ultrasonographic characteristics. However, patients with invasive eFV-PTC had higher preoperative neutrophil-to-lymphocyte ratio (NLR) values and a higher Bethesda cytology category compared to those with NIFTP. In the multivariable analysis, NLR was the only significant predictor of invasive eFV-PTC. Nevertheless, there was no reliable NLR cutoff for distinguishing between the two entities. Overall, this study substantiates considerable overlap in demographic and clinical data between NIFTP and invasive eFV-PTC. Although the higher NLR observed in thyroid cancer does not provide strong discrimination, it suggests that the invasive nature of tumor cells might elicit a more profound systemic inflammatory or immune response.

Acute and chronic systemic inflammation associated with canine nodular splenic lesions composed of heterogeneous cell components: four cases (2020‐2024)

ObjectivesTo describe the clinical presentation and clinicopathological findings of dogs with nodular splenic lesions composed of heterogeneous cell components associated with systemic inflammation and to provide information on the outcome after surgical resection.Materials and MethodsMedical records were searched for dogs with histologically and immunohistochemically characterised nodular splenic lesions with mixed stromal, histiocytic and lymphoid cells and the presence of systemic inflammatory markers at the time of diagnosis.ResultsFour dogs were included, of which three had an undifferentiated splenic stromal sarcoma and one had a splenic leiomyosarcoma. Fever and abdominal pain were reported in three and four cases, respectively. All dogs showed hyperglobulinaemia and marked changes in the serum protein electrophoresis profile. C‐reactive protein and fibrinogen concentrations were both increased in three cases. These abnormalities completely resolved after splenectomy. Moreover, two dogs had concomitant glomerular disease and one dog had liver amyloidosis. Three dogs were still alive and asymptomatic 1, 6 and 9 months after surgery. One dog died 16 months after the initial presentation due to complications related to progressive renal failure.Clinical SignificanceBased on this report, nodular splenic lesions with heterogeneous cell components may directly be associated with a pro‐inflammatory state and should be considered as part of the differential diagnosis of fever and hyperglobulinaemia in dogs. Furthermore, early recognition and treatment of these lesions could reduce the risk of systemic complications potentially associated with amyloid deposit and organ failure.

Lipid-encapsulated gold nanoparticles: an advanced strategy for attenuating the inflammatory response in SARS-CoV-2 infection

BackgroundNanodrugs play a crucial role in biomedical applications by enhancing drug delivery. To address safety and toxicity concerns associated with nanoparticles, lipid-nanocarrier-based drug delivery systems have emerged as a promising approach for developing next-generation smart nanomedicines. Ginseng has traditionally been used for various therapeutic purposes, including antiviral activity. This study aimed to prepare a biocompatible and therapeutically potent Korean ginseng nanoemulsion (KGS-NE) using ginseng seed oil (GSO), optimize its encapsulation and drug delivery efficiency, and evaluate its antiviral activity.ResultsVarious techniques were utilized to confirm the KGS-NE formation. Energy-dispersive X-ray spectroscopy identified gold nanoparticles with the highest Au peak at 2.1 keV. Selected area diffraction patterns revealed crystallographic structures. FT-IR spectrometry detected functional groups, with peaks at 2922.09 cm−1 (alkene C–H stretching), 1740.24 cm−1 (aldehyde C=O stretching), and 1098.07 cm−1 (C–O stretching in secondary alcohol). Storage stability studies showed that KGS-NE maintained its size and stability for 6 months at 4 °C. The KGS-NE exhibited a dose-dependent suppression of HCoV-OC43 viral replication in Vero E6 cells. RNA sequencing analysis unveiled differentially expressed genes (DEGs) specifically involved in the ABC transporters signaling pathway. KGS-NE oral administration facilitated the recovery of mice induced with the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, as confirmed by inflammatory markers expression in lung tissue. In the Syrian hamster infected with the SARS-CoV-2 model, the lungs dissected showed enlarged morphology and induced inflammatory cytokines. This effect was mitigated with KGS-NE oral administration, as observed through H&E and qRT-PCR analysis. Biochemical analysis at various oral administration concentrations demonstrated that KGS-NE had no adverse effects on the kidney and liver.ConclusionsOur findings strongly suggest that oral administering KGS-NE in mice and Syrian hamster models has the potential to effectively mitigate lung inflammation against coronavirus. This indicates a promising new strategy for developing the antiviral nano-agent against SARS-CoV-2.Graphical

Identifying Novel Aging-Related Biomarkers for Age-related Macular Degeneration with Integrative Bioinformatics Approaches

Age-related macular degeneration (AMD) is the leading cause of visual impairment in older adults worldwide and is a condition that causes visual deprivation. There exist two subcategories of this disease with the wet form of this disease being the focus of our study. Using bioinformatic analysis, this research conducted investigations to uncover the genes related to aging that may be biomarkers for the development of AMD. First, we compared the expression levels of samples from AMD/CNV patients and a control group using the GEO microarrays (GSE29801) in order to obtain differentially expressed genes (DEGs). WGCNA, combined with functional enrichment analysis, is utilized to discover and validate the gene module crucial for AMD. Differentially expressed aging-related genes (DEARGs) were identified by overlapping significant gene sets. The subcellular location of hub DEARGs and their corresponding cell subpopulations were determined and predicted using the Geo dataset GSE155288. Pan-cancer analyses were used to confirm those hub DEARGs function in other diseases. Moreover, both Protein-Protein Interaction (PPI) and AlphaFold prediction were employed to validate the protein interaction among the key DEARGs. Lastly, a potential target drug was selected, with portions of them validated through drug-protein interactions. In further analysis of our result, the collect gene set of 7 DEARGs was divided into the immune-related group and the non-immune-related group. These groups uncovered two distinct pathways of AMD development, with one triggering inflammatory responses by promoting macrophage proliferation and the other inducing choroidal neovascularization formation due to malfunctioning growth regulator genes