Inflammatory Cells Research Articles

Sex and Age-Dependent Effects of miR-15a/16-1 Antagomir on Ischemic Stroke Outcomes

Ischemic stroke is a leading cause of disability and mortality worldwide. Recently, increasing evidence implicates microRNAs (miRs) in the pathophysiology of ischemic stroke. Studies have shown that miR-15a/16-1 is abnormally expressed in brains after ischemic stroke, and its upregulation may increase ischemic damage. Given that sex and age are significant modifiers of stroke outcomes, here we investigated whether inhibiting miR-15a/16-1 with antagomirs mitigates cerebral ischemia/reperfusion (I/R) injury in a sex- and age-dependent manner. Young (3 months) and aged (18 months) male and female C57/BL mice underwent 1-h middle cerebral artery occlusion and 3–7 days reperfusion (tMCAO). We administered miR-15a/16-1 antagomir (30 pmol/g) or control antagomir (NC, 30 pmol/g) via tail vein 2 h post-MCAO. Neurobehavioral testing and infarct volume assessment were performed on days 3 and 7. Compared to controls, antagomir treatment significantly improved neurobehavioral outcomes and reduced infarct volume in tMCAO mice at day 7, with the effects being more pronounced in young mice. Notably, young female mice exhibited superior survival and sensorimotor function compared to young male mice. These results were also replicated in a permanent MCAO (pMCAO) mice model. This suggests miR-15a/16-1 antagomir and estradiol may synergistically regulate genes involved in neurovascular cell death, inflammation, and oxidative stress, with sex and age-dependent expression of miR-15a/16-1 and its targets likely underlying the observed variations. Overall, our findings identify miR-15a/16-1 antagomir as a promising therapeutic for ischemic stroke and suggest that sex and age should be considered when developing miR-based therapeutic strategies.

Unveiling the efficacy and mechanism of Danggui-Shaoyao-San in treating nephrotic syndrome: A meta-analysis and network pharmacology study

Aim of the studyThe purpose of this study was to investigate the efficacy and mechanism of DSS in treating nephrotic syndrome through meta-analysis and network pharmacology methods. Materials and methodsTo conduct a comprehensive search for randomized controlled trials on the efficacy of Danggui Shaoyao San (DSS) in the treatment of nephrotic syndrome, we searched across eight electronic databases from their establishment to May 1, 2023. The Cochrane Collaboration's Risk of Bias 2 tool was used to evaluate the quality of evidence regarding bias risk and outcomes. Statistical analysis was performed using RevMan software (version 5.4). Furthermore, network pharmacology was employed to validate the underlying mechanism. ResultsThis study included 14 articles that involved 1256 patients with nephrotic syndrome. The clinical efficacy of DSS against nephrotic syndrome was significantly higher than that of Western medical treatment alone. In comparison with the control groups, which were administered Western medicines alone, the use of DSS significantly increased plasma albumin levels (mean difference [MD] = 4.32, 95 % confidence interval [CI] [2.37, 6.24], p < 0.00001) and reduced 24 h urinary protein excretion (MD = −0.92, 95 % CI [−1.11, −0.73], p < 0.00001), total cholesterol levels (MD = −1.23, 95 % CI [−1.76, −0.70], p < 0.00001), triglyceride levels (MD = −0.37, 95 % CI [−0.54, −0.20], p < 0.00001). Furthermore, the combination of DSS with Western medicines achieved better control of adverse reactions in comparison with the control groups (relative risk = 0.37, 95 % CI [0.29, 0.49], p < 0.00001). Network pharmacology analysis identified 39 important active compounds and 18 core target genes involved in the treatment of primary nephrotic syndrome by DSS. Gene Ontology enrichment analysis identified 2126 biological processes, 64 cellular components, and 115 molecular functions, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified 149 signaling pathways. Key active compounds include ginsenoside Rg5, ginsenoside Rg1, schisandrin A, berberine, gallic acid, quercetin, and β-sitosterol, while potential core target genes include IL6, AKT1, TNF, VEGFA, IL1B, and TP53. KEGG pathway analysis indicated that DSS is involved in multiple mechanisms, such as neural development, synaptic plasticity, programmed cell death, inflammation, and immunity. ConclusionsDSS has higher efficacy and safety in the treatment of nephrotic syndrome and acts on nephrotic syndrome via mechanisms that involve multiple targets, components, and pathways.

Infections in Inborn Errors of STATs

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is highly conserved and essential for numerous biological functions triggered by extracellular signals, including cell proliferation, metabolism, immune response, and inflammation. Defects in STATs, either loss-of-function or gain-of-function defects, lead to a broad spectrum of clinical phenotypes in humans, including a wide range of infectious complications. The susceptibility to pathogens can stem from defects in immune cells within the hematopoietic compartment, impaired barrier functions of non-hematopoietic compartment, or a combination of both, depending on the specific STAT defect as well as the pathogen exposure history. Effective management involves antimicrobial prophylaxis tailored to the patient’s infection risk and improving disease control with targeted therapies and/or hematopoietic cell transplantation.

Gypenosides alleviates HaCaT keratinocyte hyperproliferation and ameliorates imiquimod-induced psoriasis in mice

Background: Psoriasis is an autoimmune skin condition characterized by hyperproliferation of keratinocytes and chronic immune responses. Gypenosides (Gyp) exhibits anti-proliferative and anti-inflammatory effects on different diseases. However, its functioning and mechanism of Gyp on psoriasis remains unknown. Objective: To explore the effect and mechanism of Gyp on psoriasis. Material and Methods: The impact and mechanism of Gyp on psoriasis in vitro and in vivo were probed through cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, reverse transcription quantitative polymerase chain reaction, hematoxylin and eosin staining, enzyme-linked immunosorbent serologic assay, immunofluorescence, and Western Blotting assays. Results: Gyp inhibited cell proliferation and the release of inflammatory cytokinesin interleukin (IL-22)-induced spontaneously transformed human aneuploid immortal keratinocyte cell line (HaCaT). In addition, Gyp demonstrated enhancement in erythema and scaling as well as reductions in the thickness of epidermal layers, release of inflammatory factors, and Ki-67 (a nuclear protein) level in imiquimod (IMQ)-induced mice. Mechanistically, Gyp upregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) expression and diminished the level of p-p65/p65 and p-STAT3/STAT3 in skin tissues from IMQ-induced mice and IL-22-induced HaCaT cells, which were reversed with the application of ML385, an inhibitor of Nrf2. In addition, the administration of ML385 reversed decrease in cell viability and reduced the expressions of IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in IL-22-induced HaCaT cells caused by Gyp. Conclusion: In summary, Gyp reduced excessive cell growth and inflammation in psoriasis by suppressing nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) through activation of Nrf2.

Berberine ameliorates inflammation by inhibiting MrgprB2 receptor-mediated activation of mast cell in mice

BackgroundBerberine, an isoquinoline alkaloid, is known for anti-inflammatory activities. However, the research on the anti-inflammatory mechanism of berberine is not comprehensive. Recently, studies have shown that MrgprB2 (Mas-related G-protein-coupled receptor B2) in mice and MrgprX2 (Mas-related G-protein-coupled receptor X2) in humans play vital roles in inflammation. Therefore, this study aims to investigate whether the anti-inflammatory activity of berberine is related to MrgprB2 receptor. MethodsThe anti-inflammatory activity of BH (berberine hydrochloride) was evaluated by hindpaw edema analysis, pathological analysis and RT-qPCR. Transgenic mice (MrgprB2−/− mice), HEK293T cell transfection, calcium imaging, electrophysiology, molecular docking and other methods were employed to investigate the potential relationship between the anti-inflammatory activity of BH and the MrgprB2 receptor. ResultsThe results demonstrated that BH significantly alleviated C48/80 (compound 48/80)-induced local inflammation in vivo. This was evidenced by a decrease in paw edema, reduced infiltration of inflammatory cells, inhibition of mast cell activation, and down-regulation of inflammatory factors such as CXCL13 (CXC subfamily 13) and TNF-α (tumor necrosis factor-α). It was also found that knockout of MrgprB2 receptor could block the anti-inflammatory activity of BH in mice. Furthermore, calcium imaging revealed that BH effectively inhibited the activity of MrgprB2 receptor in overexpressed HEK293T cells in vitro. Additionally, it was observed that BH also inhibited MrgprB2-mediated voltage-dependent current changes in mouse peritoneal mast cells. Molecular docking results further indicated that BH had affinity with MrgprX2 protein. ConclusionsThe anti-inflammatory mechanism of BH may be partially attributed to the inhibition of MrgprB2 receptor-mediated mast cell activation.

The Effects of Turmeric and Mangosteen Pericarp Ethanol Extract on Eosinophil Count, TNF-α and TGF-β1 Gene Expression in Asthmatic Rat Model.

Asthma is a chronic respiratory disease that is characterized by inflammation, bronchial hyperreactivity, and airway remodeling. The long-term use of corticosteroids at high doses causes various side effects. Traditional herbal medicine has been suggested as an alternative therapy that is safe and effective in dealing with asthma. Natural plants such as turmeric and mangosteen are known to treat asthma and reduce inflammation. The purpose of this study was to investigate the effects of turmeric and mangosteen pericarp ethanol extracts on the eosinophil counts, TNF-α and TGF-β1 gene expression, and inflammatory cell counts in the histopathology of an asthmatic rat model. The preliminary study used 30 rats, which were divided into a normal group, negative control group (OVA-sensitized), turmeric normal group, mangosteen group, and positive control group. Blood samples were collected after the sensitization period to determine eosinophil counts. TNF-α and TGF-β1 gene expression, and histopathology were observed in the rat's lungs. The follow-up study used 30 rats divided into a normal group, negative control group (OVA-sensitized), combination of turmeric and mangosteen group (54m/200gr rats, 36mg/200gr rats, and 36mg/200gr rats), and positive control group. The examination procedures were the same as in the preliminary study. The administration of single ethanol extracts of turmeric and mangosteen significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p<0.05). The combination of turmeric and mangosteen extracts at all doses significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p<0.05). Both the single and combined administration of turmeric and mangosteen ethanol extracts did not cause significant changes in TNF-alpha and TGF-beta (p>0.05). Turmeric ethanol extract and mangosteen pericarp ethanol extract have a reductional effect on the parameters of asthma based on the eosinophil counts, the inflammatory cell counts and score, and bronchial smooth muscle thickness.

Ultrasound-targeted sirolimus-loaded microbubbles improves acute rejection of heart transplantation in rats by inhibiting TGF-β1-Smad signaling pathway, promoting autophagy and reducing inflammation

Acute rejection (AR) remains a pivotal complication and leading cause of mortality within the first year following heart transplantation (HT). In this study, we assessed the impact of ultrasound-targeted microbubbles loaded with sirolimus (SIR-MBs) on AR in a rat HT model and delved into the underlying mechanisms. We established a rat abdominal ectopic HT model, which was stratified into three groups receiveing the PBS, SIR-MBs + ultrasound-targeted microbubble destruction (UTMD), and sirolimus, respectively. The protective effects of each treatments on survival rate, inflammatory response, autophagy and TGF-β1-Smad signaling pathway-related proteins were evaluted. Additionally, rescue experiment was performed via adding the autophagy inhibitor or TGF-β1 agonist in combination therapy. UTMD combined SIR-MBs mediated 15-fold higher local drug concentration compared to direct sirolimus administration. The infiltration of inflammatory cells in the transplanted hearts indicated that SIR-MBs combined with UTMD were effective in mitigating the inflammatory response, achieving levels significantly lower than those observed in the sirolimus group. Furthermore, after SIR-MBs combined with UTMD treatment, the expression levels of TGF-β1-Smad signaling pathway-related proteins in heart tissues also showed a significant decrease compared to the model control group. Conversely, the expressions of autophagy proteins LC3-II, Beclin-1 and β-arrestin showed an up-regulated trend. Rescue experiments also revealed that the enhancement in survival trends was markedly suppressed following the administration of CsA or SRI-011381, respectively. Collectively, our findings suggest that SIR-MBs combined with UTMD augment the local treatment efficacy for AR in rat HT models by inhibiting the TGF-β1-Smad signaling pathway, promoting autophagy, and alleviating inflammation.

The oxidized hyaluronic acid hydrogels containing paeoniflorin microspheres regulates the polarization of M1/M2 macrophages to promote wound healing

Controlling excessive inflammation of acute wound is an effective means to shorten the healing time. Therefore, targeted control of the inflammatory response of the wound is a promising therapeutic strategy. In this study, paeoniflorin (Pae) was encapsulated in microspheres and combined with oxidized hyaluronic acid hydrogels to prepare the hydrogel loaded with Pae microspheres (Pae-MPs@OHA) to promote the healing of acute wounds in rats. The results demonstrated that the particle size of the Pae-MPs was 6.84 ± 0.51 μm, and the positive charge was 26.87 ± 1.51 mV. The uniform spherical structure of the Pae-MPs was observed by TEM. The Pae-MPs@OHA can maintain colloidal state in the range of 0.1–3.16 Hz. FTIR suggested that Pae could be effectively wrapped in MPs, and SEM indicated that the Pae-MPs@OHA had a uniform network pore structure. The Pae-MPs@OHA can realize the sustained release of Pae for 96 h. Biocompatibility experiments showed that the Pae-MPs@OHA hydrogels were safe and available. The Pae-MPs@OHA hydrogels can accelerate wound healing in rats. HE and masson staining suggested that the Pae-MPs@OHA could reduce inflammatory cell infiltration, promote re-epithelialization and collagen formation. The Pae-MPs@OHA could decrease the number of M1 and increase the number of M2 in macrophages, thus regulating the release of inflammatory factor TNF-α and IL-1β. The results of molecular docking and western blot results also confirmed that the Pae-MPs@OHA could reduce the expression of NF-κB, pNF-κB, NLRP3, ASC and pro-caspase-1. These findings suggest that the Pae-MPs@OHA has great potential for application in the treatment of inflammatory wound.

Subtype prevalence and treatment implication in adolescents and adults with mild-to-moderate asthma: A systematic review and meta-analysis

BackgroundInhaled corticosteroid (ICS) containing regimens are the mainstay for treating asthma despite usually being ineffective in non-eosinophilic asthma (NEA). Data on the prevalence of NEA versus eosinophilic asthma (EA) in mild-to-moderate asthmatics is limited. ObjectiveTo systematically review the subtype prevalence of mild-to-moderate asthma in adolescents and adults using sputum inflammatory cell analysis and their responses to ICS. MethodsWe searched electronic databases (PubMed, Scopus, EMBASE, Cochrane) for studies in adolescents and adults with mild-to-moderate asthma. The primary outcome was the prevalence of asthma subtypes based on sputum inflammatory cell analysis, categorized into EA and NEA. The secondary outcome involved comparing asthma outcomes between different subtypes following ICS therapy. Certainty of evidence was reported for each pooled analysis. ResultsEighteen studies involving 3,533 adolescents and adults with mild-to-moderate asthmatics were reviewed. The pooled prevalence (95% confidence interval, CI) of NEA was estimated at 40.39% (27.54, 53.93) in patients with ICS naïve with very low certainty of evidence. Upon reevaluating sputum cytology, approximately 20% to 30% of patients initially classified as having NEA transitioned to the EA subtype. EA patients showed significant improvements in asthma symptoms, FEV1 [standardized mean difference (95% CI): 0.79 (0.30, 1.27)], and airway hyperresponsiveness [1.34 (0.29, 2.40)] following ICS therapy, while NEA patients exhibited limited response. ConclusionA high proportion of adolescents and adults with mild-to-moderate asthma were identified as having the NEA subtype, which exhibited a poor response to ICS. A thorough diagnostic evaluation before initiating treatment should be integrated into clinical practice.

Lysophosphatidylcholine Acyltransferase 2 Contributes to Increased Allergic and Irritant Inflammation in Mice

ABSTRACTPlatelet‐activating factor (PAF) is an important chemical mediator in the field of inflammation, but its function in the skin is unclear. To unravel the role of PAF, we focused on lysophosphatidylcholine acyltransferase 2 (LPCAT2 also called LPLAT9), a biosynthetic enzyme involved in PAF production, and investigated the role of PAF in allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). We measured the amount of PAF in the skin and investigated the ear swelling responses and leukocyte infiltration into the skin following the application of 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) or croton oil in wild‐type (WT) and LPCAT2 knockout (LPCAT2‐KO) mice. The amount of PAF was increased in the skin of WT mice after TNCB or croton oil application but not detected in LPCAT2‐KO mice. The ear swelling response was decreased in LPCAT2‐KO mice compared with that in WT mice. In the ACD model, the numbers of lymphocytes, eosinophils, macrophages, mast cells and neutrophils were smaller in LPCAT2‐KO mice than in WT mice. In the ICD model, the ear swelling response was also decreased in LPCAT2‐KO mice compared with that in WT mice. When double staining of each inflammatory cell type and LPCAT2 was performed in ACD tissue, marked co‐staining of the eosinophil marker and LPCAT2 was observed. In addition, LPCAT2 expression was observed in the epidermis. These results indicate that PAF is involved in the infiltration of several cell types into the sites of allergic and non‐allergic skin inflammation. Furthermore, eosinophils and keratinocytes are primarily responsible for PAF production in skin inflammation.

Protective effect of Huashi Baidu formula against AKI and active ingredients that target SphK1 and PAI-1

BackgroundHuashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF.MethodsThe present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system.ResultsIn the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF.ConclusionIn brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for broadening the clinical applications of HBF and unravelling its molecular mode of action.

Comparison of the Predictive and Prognostic Capacities of Neutrophil, Lymphocyte and Platelet Counts and Tumor-infiltrating Lymphocytes in Triple-negative Breast Cancer: Preliminary Results of the PERCEPTION Study.

Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype, posing numerous challenges in clinical decision-making. Biomarkers are essential to personalize management of TNBC patients. While tumor infiltrating lymphocytes (TILs) are validated prognostic biomarkers, the requirement for tumor biopsy limits their routine use. Therefore, more accessible and reliable quantitative biomarkers are needed. Given the significant role of systemic inflammatory response in tumor onset and progression, assessing inflammatory cells via liquid biopsies emerges as a promising alternative. The PERCEPTION study, conducted at Centre Jean Perrin in France, aims to determine the correlation between TILs and peripheral blood components at diagnosis. An interim analysis was conducted after enrolling 50% of the estimated population, to evaluate study feasibility and preliminary correlations between blood cell counts and TILs. Sixty-one patients were enrolled over 4.5 years, demonstrating a good inclusion rate with minimal missing data. Preliminary results for 36 analyzable patients showed no correlation between the neutrophil-to-lymphocyte ratio (NLR) and TILs (rs=-0.19, 95%CI=-0.49-0.16, p=0.3). However, a moderate, positive, statistically significant correlation was found between NLR and the CD8/FoxP3 TILs ratio (rs=0.36, 95%CI=0.03-0.64, p=0.043). The probabilistic index of 0.7 (p=0.06) between NLR-high and NLR-low groups for this ratio supports the correlation. The interim analysis of the PERCEPTION study confirms the feasibility of correlating blood cell counts with TILs in TNBC. Although no significant correlation was observed between NLR and TILs, the moderate positive correlation between the CD8/FoxP3 ratio and TILs suggests a potential link between systemic inflammation and local immune response. These findings underscore the potential of blood-based markers as non-invasive surrogates for TILs, encouraging further research to enhance prognosis and guide treatment strategies in TNBC.

Clinical and Histopathological Characteristics of Patients With Myocarditis After mRNA COVID-19 Vaccination.

The effects of myocarditis after mRNA COVID-19 vaccination (mCV) on myocardial tissue, and the association between cardiomyocyte injury and clinical presentation, are not fully understood. We retrospectively registered patients clinically diagnosed with myocarditis after the first or second mCV who underwent endomyocardial biopsy or autopsy from 42 participating centers in Japan. We investigated the histological features and their association with clinical presentation based on cardiomyocyte injury. Forty patients who underwent endomyocardial biopsy were included in the study. Of these, 19 (47.5%) showed mild lymphocytic infiltration and interstitial edema without cardiomyocyte injury. The remaining 21 (52.5%) patients showed cardiomyocyte injury accompanied by infiltrating inflammatory cells: 11 with lymphocytic infiltration, 7 with eosinophilic infiltration, and 3 with myocarditis with both lymphocyte and eosinophil infiltration. Compared with patients without cardiomyocyte injury, those with cardiomyocyte injury were clinically characterized by older age, a balanced sex distribution, less frequent chest pain, and a lower left ventricular ejection fraction. Fifteen of 21 (71.4%) patients with cardiomyocyte injury developed fulminant myocarditis, with 13 (86.7%) requiring mechanical circulatory support; in contrast, none of those without cardiomyocyte injury developed fulminant myocarditis (P<0.001). Our histological examination of patients with myocarditis after mCV revealed varying degrees of cardiomyocyte injury, ranging from pronounced to absent, along with various types of myocarditis. Cardiomyocyte injury was strongly associated with the severity of myocarditis.

Diagnosis and hormonal treatment of cystic ovaries associated with uterine disorders in Egyptian buffaloes: ultrasonography, histopathological and serological investigations

Cystic ovarian disease (COD) with uterine abnormalities is a postpartum reproductive pathology in Egyptian buffaloes causing significant economic losses. In this study, we aimed to employ various diagnostic methods for detecting cystic ovarian disease (COD) in Egyptian buffaloes. tour study assessed the effectiveness of the GnRH/PGF2α protocol as a treatment strategy. Our goal was to determine if this protocol could effectively reduce economic losses associated with cystic ovarian disease and improve herd fertility in Egyptian buffaloes. Eighty Egyptian buffalo cows were included in this study. They were identified to have follicular cysts through rectal examination, which was confirmed by ultrasonography. These buffaloes were then divided into two main groups: the COD Control (untreated) (GA) (n = 40) and COD group (GB) (n = 40) treated with GnRH/PGF2α. According to our immunological studies, buffaloes in the COD-treated group (GB) exhibited significantly lower serum levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) compared to the control group. This observation was consistent with the decline in E2 levels and the increase in P4 levels (p < 0.01–0.001) observed in the treated animals compared to the untreated group. Furthermore, serum cortisol and glucose concentrations decreased in COD-treated buffaloes. Histopathological examination of ovaries and uterine tissue from slaughtered COD buffaloes has revealed significant structural alterations. These include the presence of ovarian cysts of varying sizes with vacuolar degeneration. Additionally, lymphoplasmacytic endometritis was observed in the uterine tissue of affected animals, featuring degeneration and desquamation of the endometrial lining accompanied by infiltration of mononuclear inflammatory cells. Severe and prolonged cases of COD, which did not respond to treatment, exhibited marked adverse pathological changes upon histopathological assessment of the genital tract. In conclusion, hormonal treatment with GnRH/PGF2α appears to be effective in treating COD-affected animals. The study provides valuable insights into the immunological, biochemical, and histopathological aspects of cystic ovaries associated with uterine disorders in Egyptian buffaloes, while also evaluating hormonal treatment for cystic ovarian disease as a means to minimize economic losses and improve herd fertility in this species.

Plastic bronchitis associated with human bocavirus 1 infection in children.

Plastic bronchitis (PB) is a clinical-pathological syndrome characterized by the abnormal accumulation of endogenous substances in the bronchial airways, causing partial or complete obstruction and resulting in impaired lung ventilation. In this retrospective analysis, we aim to summarize the clinical manifestations, imaging characteristics, diagnostic methods, and treatment approaches to enhance clinicians' ability to detect children who are infected withhuman bocavirus 1(hBoV 1) and develop PB. In the period from January 2021 to January 2024, a total of six hBoV 1 infection children were diagnosed with PB through bronchoscopy. The onset of the condition was mainly concentrated between June and December. The detection methods used included metagenomic next-generation sequencing for pathogen identification (three cases) and respiratory pathogen nucleic acid 13-plex detection (oropharyngeal swab) (three cases), both of which confirmed the presence of hBoV 1. Out of the six children with PB, two were girls and four were boys. Their ages ranged from 10 months to 4 years old. Common symptoms reported by all patients included fever, cough,and wheezing. Chest high-resolution computed tomography scans revealed atelectasis in six cases, in addition to pneumonia. After the removal of the plastic bronchi via bronchoscopy, the airway obstruction symptoms in the children were relieved, and no recurrence was observed during the follow-up period. Pathological findings indicated cellulose exudation and inflammatory cell infiltration, consistent with nonlymphatic PB. When children infected with hBoV 1 exhibit persistent or worsening symptoms such as cough, fever, and wheezing despite treatment, clinicians should remain highly vigilant for the potential occurrence of PB. Bronchoscopy plays a crucial role not only in diagnosing the presence of a plastic bronchus but also in effectively treating PB.

Impact of Dual-coated Silver Nanoparticle and Antibiotic Sutures on Wound Healing in Inflammatory Mouse Models

ABSTRACT Background: The use of silver nanoparticles (AgNPs) in biomedicine has emerged in a big way owing to its antibacterial and anti-inflammatory properties. We hypothesize that combining the AgNPs with antibiotics for coating sutures will enhance the antibacterial property of sutures with the added advantage of the immunomodulatory effect of AgNPs on tissue healing. Materials and Methods: Polyglactin sutures were coated with AgNPs using the dip-coating method. The uniform coating and morphology of AgNPs on the suture surface were confirmed using scanning electron microscopy (SEM). Each type of suture – polyglactin plain, antibiotic coated (Triclosan), AgNP coated, and dually coated (antibiotic and AgNP) – was assessed for their antibacterial properties against Gram-positive bacteria, Gram-negative bacteria, and anaerobes. These sutures were utilized in an abdominal and systemic inflammatory mice model for ileal anastomosis. The intestinal tissue was evaluated for acute and chronic inflammation and collagen deposition to assess the healing and inflammatory response. Results: The SEM and energy dispersive X-ray analysis showed successful coating of AgNPs on plain and antibiotic-coated sutures. In comparison with the other groups, the dually coated suture had the best in vitro antibacterial efficacy. The AgNP-coated sutures were able to decrease both acute and chronic inflammatory cell infiltration, but the collagen synthesis and deposition were enhanced. Conclusion: AgNPs can be coated on Polyglactin suture either alone or in combination with antibiotics with preserved antibacterial effects. The dual coating of sutures gives a synergistic antibacterial effect. The AgNP diminishes immune response in the presence of preserved extracellular matrix generation.

Tubercular dactylitis/Spina ventosa-A rare skeletal form of extrapulmonary tuberculosis.

A 9-year-old girl presented with progressive, painful swelling over the left index finger, associated with local signs of inflammation and restriction of finger movements. After the swelling was punctured using a needle, chronic discharging sinus formed. Examination revealed firm swelling over the right parotid area, bilateral cervical and left axillary lymphadenopathy, and firm swelling over the left index finger with a chronic discharging sinus over the lateral aspect of proximal phalanx. Mantoux intradermal injection was reactive (22x24 mm induration). Blood and pus cultures were sterile. Hand radiograph revealed dactylitis (Figure 1A-C). Fine aspiration and cytology of the cervical lymph node showed degenerated inflammatory cells, epithelioid granuloma and acid-fast bacilli. She was initiated on 4-drug antitubercular therapy (ATT). At 2-months follow-up, she was asymptomatic and had the pain and swelling over the left finger have reduced with significant radiological improvement. Tubercular dactylitis or 'spina ventosa' (wind-filled sail) refers to cystic expansion of short, tubular bones. It is commonly seen in younger children (between 1 and 6 years of age) and adults (between 20 and 50 years of age). A common presentation in endemic areas is presence of a painless, fusiform swelling over a single digit, most commonly the proximal phalanx of index or middle finger as in the index case, or over the metacarpals of middle and ring fingers. Earliest radiological clues include periosteitis followed by gradual destruction of bone and cyst formation in the cavity giving a ballooned-out appearance.

HUCMSC-derived exosomes mitigate blood-spinal cord barrier disruption by activating AMPK/mTOR-mediated autophagic flux after acute spinal cord injury

After spinal cord injury (SCI), the integrity of the blood-spinal cord barrier (BSCB) can be disrupted, leading to the secondary injuries such as inflammatory cell infiltration, neuronal death, and spinal cord hematoma. It is important to maintain the integrity of the BSCB to help restore function following SCI. While some studies have demonstrated the therapeutic effects of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos), their role in preserving BSCB integrity remains unclear. In our study, we demonstrated the protective effects of hUCMSC-exos on the BSCB and its mechanism. The results of this study indicate that hUCMSC-exos promote motor function recovery, preserve spinal cord structure, and reduce neuronal loss by inhibiting BSCB leakage following SCI. Experimental investigations conducted in vivo and in vitro have demonstrated that hUCMSC-exos can mitigate the loss of adherens junctions (AJs) and tight junctions (TJs) and stimulate autophagy in spinal cord endothelial cells. The protective effects were also found to be significantly reversed following the inhibition of autophagy using 3-MA. In conclusion, our study demonstrates that hUCMSC-exos protect the integrity of BSCB by promoting the repair of spinal endothelial cells through activation of autophagy, thereby exerting a protective role in SCI.

Choroid Plexus Volume in Pediatric-Onset Multiple Sclerosis.

Recent studies suggest that the choroid plexus (CP) may function as a site of access of inflammatory cells into the CNS in multiple sclerosis (MS). Pediatric-onset MS (POMS) is characterized by a high inflammatory burden, as evidenced by a high relapse rate and volume of T2 lesions, making patients with POMS an informative population to evaluate choroid plexus volume (CPV). The objectives of the study were (1) to evaluate CPV at symptom onset in participants with POMS compared with healthy controls (HCs); (2) to evaluate changes in CPV in the first year of disease in participants with POMS; and (3) to evaluate associations between CPV, brain volumes, relapse activity, and disability in participants with POMS. Baseline 1.5T MRI scans were acquired from 23 participants with POMS and 23 age-matched and sex-matched HCs; 18 participants with POMS also had 12-month follow-up MRI scans. The CP of the lateral ventricles was segmented manually. CP and brain structure volumes were normalized for total intracranial volume. The number of relapses, T2 and gadolinium-enhancing T1 lesion counts, and Expanded Disability Status Scale (EDSS) scores at 12 months were also analyzed. Baseline CPVs were compared between groups using the Wilcoxon exact test, and CPV change from baseline to 12 months in participants with POMS was compared using the Wilcoxon signed-rank test. The relationship between CPV and brain volumetric measures, T2 lesion volumes, lesion count, number of relapses, and EDSS scores was assessed through Spearman correlation. The median normalized CPV was 1.51 × 10-3 (interquartile range [IQR]: 1.32-1.76) in POMS baseline scans and 1.21 × 10-3 (IQR: 1.1-1.47) in HC scans (p = 0.001). CPV did not significantly change at 12 months in the 18 participants with POMS with follow-up scans (p = 0.352). CPV in participants with POMS and HCs correlated with lateral ventricular volume (p = 0.012 for both groups) but did not correlate with brain and T2 lesion volumes or lesion count at baseline, nor with relapse activity or EDSS scores at 12 months in participants with POMS. CPV measured at baseline is greater in participants with POMS than in HCs. Baseline CPV did not predict higher disease activity or worse neurologic outcomes over 1 year. While higher CPV may be an early feature of inflammation in MS, its strong correlation with ventricular volumes could also reflect enlargement secondary to the mechanical attachment of CP to the ventricular wall.

The essential oils from Asarum sieboldii Miq. alleviate allergic rhinitis by regulating tight junction and inflammation; Network analysis and preclinical validation

Ethnopharmacological relevanceEssential oils from herbs, including those from Asarum sieboldii Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. Asarum sieboldii Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on Asarum sieboldii Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking. Aim of the studyWe utilized bioinformatics and network pharmacology to identify the effectiveness of Asarum sieboldii Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from Asarum sieboldii Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR. Materials and methodsCommon genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM10; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 minutes per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response in vitro and in vivo. ResultsThe common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA+PM10 induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM10-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways. ConclusionIntranasal nebulization of ASO improves TJs and alleviates allergic nasal inflammation in AR. It supports the potential pharmaceutical application of ASO treatment for AR.