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Infectious bronchitis virus (IBV) induces severe economic losses in chicken farms due to the emergence of new variants leading to vaccine breaks. The studied IBV strains belong to Massachusetts (Mass), Canadian 4/91, and California (Cal) 1737 genotypes that are prevalent globally. This study was designed to compare the impact of these three IBV genotypes on primary and secondary lymphoid organs. For this purpose, one-week-old specific pathogen-free chickens were inoculated with Mass, Canadian 4/91, or Cal 1737 IBV variants, keeping a mock-infected control. We examined the IBV replication in primary and secondary lymphoid organs. The molecular, histopathological, and immunohistochemical examinations revealed significant differences in lesion scores and viral distribution in these immune organs. In addition, we observed B-cell depletion in the bursa of Fabricius and the spleen with a significant elevation of T cells in these organs. Further studies are required to determine the functional consequences of IBV replication in lymphoid organs.

OBJECTIVES: There is little evidence guiding the management of grade I-II traumatic splenic injuries with contrast blush (CB). We aimed to analyze the failure rate of nonoperative management (NOM) of grade I-II splenic injuries with CB in hemodynamically stable patients. METHODS: A multicenter, retrospective cohort study examining all grade I-II splenic injuries with CB was performed at 21 institutions from January 1, 2014, to October 31, 2019. Patients >18 years old with grade I or II splenic injury due to blunt trauma with CB on CT were included. The primary outcome was the failure of NOM requiring angioembolization/operation. We determined the failure rate of NOM for grade I versus grade II splenic injuries. We then performed bivariate comparisons of patients who failed NOM with those who did not. RESULTS: A total of 145 patients were included. Median Injury Severity Score was 17. The combined rate of failure for grade I-II injuries was 20.0%. There was no statistical difference in failure of NOM between grade I and II injuries with CB (18.2% vs 21.1%, p>0.05). Patients who failed NOM had an increased median hospital length of stay (p=0.024) and increased need for blood transfusion (p=0.004) and massive transfusion (p=0.030). Five patients (3.4%) died and 96 (66.2%) were discharged home, with no differences between those who failed and those who did not fail NOM (both p>0.05). CONCLUSION: NOM of grade I-II splenic injuries with CB fails in 20% of patients. LEVEL OF EVIDENCE: IV.

Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.

Background and Aims The spleen serves as an important relay organ that releases cardioprotective factor(s) upon vagal activation during remote ischaemic conditioning (RIC) in rats and pigs. The translation of these findings to humans was attempted. Methods Remote ischaemic conditioning or electrical auricular tragus stimulation (ATS) were performed in 10 healthy young volunteers, 10 volunteers with splenectomy, and 20 matched controls. Venous blood samples were taken before and after RIC/ATS or placebo, and a plasma dialysate was infused into isolated perfused rat hearts subjected to global ischaemia/reperfusion. Results Neither left nor right RIC or ATS altered heart rate and heart rate variability in the study cohorts. With the plasma dialysate prepared before RIC or ATS, respectively, infarct size (% ventricular mass) in the recipient rat heart was 36 ± 6% (left RIC), 34 ± 3% (right RIC) or 31 ± 5% (left ATS), 35 ± 5% (right ATS), and decreased with the plasma dialysate from healthy volunteers after RIC or ATS to 20 ± 4% (left RIC), 23 ± 6% (right RIC) or to 19 ± 4% (left ATS), 26 ± 9% (right ATS); infarct size was still reduced with plasma dialysate 4 days after ATS and 9 days after RIC. In a subgroup of six healthy volunteers, such infarct size reduction was abrogated by intravenous atropine. Infarct size reduction by RIC or ATS was also abrogated in 10 volunteers with splenectomy, but not in their 20 matched controls. Conclusions In humans, vagal innervation and the spleen as a relay organ are decisive for the cardioprotective signal transduction of RIC and ATS. [ABSTRACT FROM AUTHOR]

Background: Splenic cysts are uncommon and very rarely malignant therefore their treatment isn't standardized. In case of symptomatic cysts different surgical approaches have been suggested. Primary malignant lymphoma of the spleen comprises less than 1% of non-Hodgkin's lymphomas. To our knowledge, only 203 cases of splenic large B-cell lymphoma (LBCL) have been reported to date and only 2 of them were fibrin-associated splenic cysts. Case presentation: 27-year-old model with a 19 × 13 cm splenic cyst without data of malignancy in the preliminary study and therefore treated with laparoscopic deroofing. After histological diagnosis of LBCL with a fibrin/EBV-associated splenic pseudocyst, the patient received 4 cycles of Rituximab and a laparoscopic splenectomy was performed due to resurgence of the pseudocyst. No evidence of malignancy has been found during follow up (EBV viral load every 3 months during the first year, PET-CT every 6 months during the first year and annual afterwards) performed after the splenectomy. Discussion and conclusions: The value of tumor markers and radiology for diagnosis of splenic cysts is put into question. Only 60 cases of Fibrin-associated LBCL (FA-LBCL) have been described in the literature therefore there are no treatment guidelines for them even though surgery together with systemic treatment has been the prevalent route with good results in most cases. [ABSTRACT FROM AUTHOR]

Introduction Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. Materials and Methods Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. Results In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g. neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. Conclusions BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems. [ABSTRACT FROM AUTHOR]

Brain-targeted drug delivery poses a great challenge due to the blood-brain barrier (BBB). In a previous study, we have developed a peptide-modified stealth liposome (SP-sLip) to enhance BBB penetration via the adsorption of apolipoproteins in plasma. SP is an 11-amino acid peptide derived from 25 to 35 of the Amyloid β peptide (Aβ 1–42), which is a nature ligand of apolipoproteins. Although freshly prepared SP-sLip exhibited efficient brain targeting performance, it occured self-aggregation and instability in storage. In this study, we developed a D-peptide ligand according to the reverse sequence of SP with D-amino acids, known as DSP, to improve the stability in storage. Notably, DSP exhibited a reduced tendency for self-aggregation and improved stability in comparison to the SP peptide. Furthermore, compared to SP-sLip, DSP-modified sLip (DSP-sLip) demonstrated enhanced stability (>2 weeks), prolonged blood circulation (AUC increased 44.4%), reduced liver and spleen accumulation (reduced by 2.23 times and 1.86 times) with comparable brain-targeting efficiency. Similar to SP-sLip, DSP-sLip selectively adsorbed apolipoprotein A1, E, and J in the blood to form functionalized protein corona, thus crossing BBB via apolipoprotein receptor-mediated transcytosis. These findings underscored the importance of ligand stability in the in vitro and in vivo performance of brain-targeted liposomes, therefore paving the way for the design and optimization of efficient and stable nanocarriers. DSP-sLip maintained the brain-targeted ability of SP-sLip by selectively adsorbing apolipoproteins in blood and crossing BBB via apolipoprotein receptors. Compared to SP-sLip, DSP-sLip exhibited less aggregation in storage, enhanced stability, extended blood circulation, and reduced liver/spleen accumulation in vivo [Display omitted] • DSP-sLip exhibited less self-aggregation and enhanced stability in storage compared to SP-sLip. • DSP-sLip maintained ability to absorb apolipoproteins in blood to form functionalized protein corona. • DSP-sLip had enhanced stability, prolonged circulation, reduced liver accumulation with comparable brain-targeting efficiency as SP-sLip. [ABSTRACT FROM AUTHOR]

Wang, Bowen, Mengjia Peng,, Liheng Jiang,, Fei Fang,, Juan Wang,, Yan Li,, Ruichen Zhao,, and Yuliang Wang,. A Rare Case of High-Altitude Polycythemia Complicated by Spontaneous Splenic Rupture. High Alt Med Biol. 25:247–250, 2024.—High-altitude polycythemia, a condition characterized by an increase in red blood cellRBC mass, can occur after prolonged exposure to high altitudes. While several studies have explored the complications associated with high-altitude polycythemia, there is currently no literature available on spontaneous spleen rupture caused by high-altitude polycythemia. Here, we reported a case of acute abdominal pain and hemodynamic instability in a 36-year-old male who had been residing at high altitude for 6 years, without any recent history of trauma. Computed tomography imaging revealed significant fluid accumulation in the abdomen, and a tear of the splenic capsule was identified during the following laparotomy. Subsequent evaluations confirmed the presence of polycythemia secondary to prolonged high-altitude exposure as the underlying etiology. This case served as an important reminder that high-altitude polycythemia could lead to serious complications, such as spontaneous spleen rupture. Clinicians should be aware of this potential complication and consider it in the differential diagnosis of patients presenting with abdominal pain and hemodynamic instability in this population. [ABSTRACT FROM AUTHOR]

Aging is associated with chronic oxidative stress, which contributes to the deterioration of the immune system, increasing morbidity and mortality. A positive social environment permits health maintenance and a slower rate of aging. Improvements in immune function and oxidative stress were shown in peritoneal leukocytes and organs of old mice and adult prematurely aging mice (PAM) after cohabitation with adults or exceptional non-prematurely aging mice (ENPAM), respectively, for 2 months, but adults and ENPAM experienced deterioration. This was solved by shortening the cohabitation time to 15 minutes per day for 2 months, where old mice and PAM maintained immune and redox state improvements in their peritoneal leukocytes, as well as a greater longevity, and adults and ENPAM did not show deterioration. However, it is unknown whether the positive effects of this short cohabitation are reflected in the immunity and redox state of the organs. The aim of the present study was to test whether a cohabitation of 15 minutes per day for 2 months maintains these positive effects in the organs of retired breeder female old mice and PAM and avoids the negative ones in adults and ENPAM. After cohabitation the animals were sacrificed, and the thymus and spleen were extracted to evaluate the immune function. The oxidative state was also analyzed in the spleen, liver, heart, lung, and kidney. The results show that after cohabitation, old mice and PAM improved their immunity and redox state, and adults and ENPAM showed no deterioration. This cohabitation can be suggested to improve health and slow down aging. [ABSTRACT FROM AUTHOR]

Maintaining immunoglobulin levels in the body is important to protect the body from exposure to pathogens. One effort can be made by consuming herbs containing immunomodulatory compounds, such as Cheral®, which includes a combination of herbs Phyllanthus niruri and Curcuma longa. This research aims to determine the expression of immunoglobulin M (IgM) and immunoglobulin G (IgG) following the administration of Cheral® to Wistar rats. The study was conducted in vivo, utilizing 24 healthy male Wistar rats for a 90-day treatment period. The research was divided into four treatment groups, including a control group and three dosage groups: Dose 1 (156.25 mg/kg BW), Dose 2 (312.5 mg/kg BW), and Dose 3 (468.75 mg/kg BW). IgM and IgG were isolated from the spleen and analyzed using flow cytometry. Flow cytometry data were analyzed using SPSS with a one-way ANOVA and post hoc test (p-value <0.05). The analysis showed that the relative number of IgM-producing cells in the control group was significantly higher than in the treatment groups, with a difference of 44.40%. In contrast, the relative number of IgG-producing cells in Dose 3 was significantly lower than all other treatment groups, showing a decrease of 29.21%. Overall, the expression of IgG and IgM did not differ substantially across all treatments. The lower IgG and IgM profiles compared to the control group indicate Cheral®'s ability to prevent infections and maintain the immune system of the rats throughout the treatment period. [ABSTRACT FROM AUTHOR]

The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 109/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (n = 35), nine (25.7%; 95% confidence interval 12.5–43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (n = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs. [ABSTRACT FROM AUTHOR]

This study investigates the applicability and reproducibility of shear-wave elastography (SWE) in detecting changes in tissue stiffness of canine carcasses. SWE was performed on six canines by two operators. The target organs were liver, spleen, kidney, and thigh muscles. SWE was performed ante-mortem and up to 48-hours post-mortem at specific intervals. The Mann-Whitney U-test and Spearman correlation coefficient showed insignificant correlation between gender and weight with shear-wave velocity (SWV) in ante-mortem scans. The Kruskal-Wallis H-test showed significant differences in SWV for all organs. Intraclass correlation coefficient (ICC) showed excellent correlation for all target organs except for kidneys. Pairwise comparison showed a similar SWV trend for abdominal organs. Accuracy metrics were calculated for determining the post-mortem interval using SWV values. The liver had the highest accuracy (0.69–0.83) across different post-mortem interval thresholds within the cut-off values of ≥2.0 m/s, 1.8–2.0 m/s, <1.8 m/s indicating ≤6 hours post-mortem, 12–18 hours post-mortem and >18 hours post-mortem. The spleen, kidney and thigh muscle demonstrated moderate-to-poor accuracy within the same cut-off parameters. Post-mortem SWV changes in canine solid organs, and soft tissues, particularly the liver, demonstrate a reproducible pattern, which may have value in determining the post-mortem interval. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effectiveness of management strategies for blunt splenic injuries in adult patients. Patients 18 years and older with blunt splenic injuries registered via the Trauma Quality Improvement Program (2013-2019) were identified. Management strategies initiated within 24 hours of hospital presentation were classified as watchful waiting, embolization, surgery, or combination therapy. Patients were stratified by injury grade. Linear models estimated each strategy's effect on hospital length of stay (LOS), intensive care unit (ICU) LOS, and mortality. Of 81,033 included patients, 86.3%, 10.9%, 2.5%, and 0.3% of patients received watchful waiting, surgery, embolization, and combination therapy, respectively. Among patients with low-grade injuries and compared with surgery, embolization was associated with shorter hospital LOS (9.4 days, Q <.001, Cohen's d =.30) and ICU LOS (5.0 days, Q <.001, Cohen's d =.44). Among patients with high-grade injuries and compared with surgery, embolization was associated with shorter hospital LOS (8.7 days, Q <.001, Cohen's d =.12) and ICU LOS (4.5 days, Q <.001, Cohen's d =.23). Among patients with low- and high-grade injuries, the odds ratios for in-hospital mortality associated with surgery compared with embolization were 4.02 (Q <.001) and 4.38 (Q <.001), respectively. Among patients presenting with blunt splenic injuries and compared with surgery, embolization was associated with shorter hospital LOS, shorter ICU LOS, and lower risk for mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

The recent discovery of disease caused by Nucleospora braziliensis in Nile tilapia (Oreochromis niloticus) is important as it has highlighted the high prevalence of infection and associated mortality in cultured fish. Thus, this study conducted an experimental infection of this microsporidium to evaluate pathological alterations and conduct proteomic analysis. For pathological observation, samples of brain, eyes, gall bladder, gut, heart, kidney, liver, muscle, skin, spleen, and stomach tissue, were collected, and liquid chromatography–mass spectrometry (LC-MS/MS) was performed for proteomic analysis. The most prevalent lesions were brownish color of the liver, gill filament fusion, gut ischemia, hemorrhage of the lips and fins, hepatomegaly, spleen atrophy, splenomegaly, and stomach congestion. The most common microscopic lesions were degeneration, hemorrhage, and inflammation in the brain, gills, gut, kidney, liver, muscle, spleen, and stomach. The digested peptides were identified by LC-MS/MS and the intersection of each group showed that in the spleen there were 121 exclusive proteins in the infected sample and 252 in the control, while in the kidney, 129 proteins were identified in the infected specimen compared to 83 in the control. In conclusion, this study demonstrates the proteome profile of O. niloticus kidney and spleen tissue in response to infection with N. braziliensis. [ABSTRACT FROM AUTHOR]

Improvements in therapies for heart failure with preserved ejection fraction (HFpEF) are crucial for improving patient outcomes and quality of life. Although HFpEF is the predominant heart failure type among older individuals, its prognosis is often poor owing to the lack of effective therapies. The roles of the spleen and bone marrow are often overlooked in the context of HFpEF. Recent studies suggest that the spleen and bone marrow could play key roles in HFpEF, especially in relation to inflammation and immune responses. The bone marrow can increase production of certain immune cells that can migrate to the heart and contribute to disease. The spleen can contribute to immune responses that either protect or exacerbate heart failure. Extramedullary hematopoiesis in the spleen could play a crucial role in HFpEF. Increased metabolic activity in the spleen, immune cell production and mobilization to the heart, and concomitant cytokine production may occur in heart failure. This leads to systemic chronic inflammation, along with an imbalance of immune cells (macrophages) in the heart, resulting in chronic inflammation and progressive fibrosis, potentially leading to decreased cardiac function. The bone marrow and spleen are involved in altered iron metabolism and anemia, which also contribute to HFpEF. This review presents the concept of an interplay between the heart, spleen, and bone marrow in the setting of HFpEF, with a particular focus on extramedullary hematopoiesis in the spleen. The aim of this review is to discern whether the spleen can serve as a new therapeutic target for HFpEF. [ABSTRACT FROM AUTHOR]

Introduction: This work was to explore the efficacy and safety of self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream in atopic dermatitis (AD) of spleen deficiency and dampness accumulation type. Material and method: 120 patients with this kind of atopic dermatitis were grouped: The Observation group (disease health education + basic treatment + mometasone furoate cream + self-made Decoction) and The Control group (disease health education + basic treatment + mometasone furoate cream), 60 cases in each group. The SCORAD score, serum IgE level, peripheral blood eosinophils, adverse events, recurrence rate, and total effective rate after treatment were observed.Result: Through treatment, SCORAD score of the observation group (29.96 ± 2.88) was lower as against controls (36.04 ± 3.12), p < 0.05. Through treatment, the peripheral blood eosinophil count in the observation group was (311.26 ± 50.19) 106/L, which was lower than (582.71 ± 54.75) 106/L in controls; the serum lgE of the observation group was (712.44 ± 93.32) IU/mL, which was lower than the controls (890.12 ± 81.25) IU/mL, p < 0.05. The Observation group (56/60, 93.33%) demonstrated superior total effective rate to the controls (34/60, 56.67%); The recurrence rate of the observation group was 4/60 (6.67%), which was lower than the controls 16/60 (26.67%), p < 0.05.Conclusion: Self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream to treat atopic dermatitis of spleen deficiency and dampness accumulation type has significant efficacy and good safety. [ABSTRACT FROM AUTHOR]

Background: To evaluate the causal relationship between abdominal multiorgan iron content and PD risk using publicly available genome-wide association study (GWAS) data. Methods: We conducted MR analysis to assess the effects of iron content in various abdominal organs on PD risk, followed by reverse analysis. Additionally, MVMR analysis evaluated the independent effects of organ-specific iron content on PD. We utilized genetic variation data from the UK Biobank, including liver iron content (n = 32,858), spleen iron content (n = 35,324), and pancreas iron content (n = 25,617), as well as summary-level data for Parkinson's disease from the FinnGen (n = 218,473) and two other large GWAS datasets of European populations (First dataset n = 480,018; Second dataset n = 2,829). The primary MR analysis used the inverse variance-weighted (IVW) method, confirmed by MR-Egger and weighted median methods. Sensitivity analysis was performed to address potential pleiotropy and heterogeneity. Observational cohort results were validated through replication cohort analysis, followed by meta-analysis. Results: IVW analysis revealed a causal relationship between increased liver iron content and elevated risk of PD (OR = 1.27; 95% CI: 1.05-1.53; p = 0.015). No significant causal relationship was observed between spleen (OR = 1.00; 95% CI: 0.76-1.32; p = 0.983) and pancreatic (OR = 0.93; 95% CI: 0.72-1.20; p = 0.573) iron content and increased risk of PD. Meta-analysis of GWAS data for PD from three different sources using the random-effects IVW method showed a statistically significant causal relationship between liver iron content and the occurrence of PD (OR = 1.17, 95% CI: 1.01-1.35; p = 0.012). Conclusion: This study presents evidence from Mendelian randomization (MR) analysis indicating a significant causal link between increased liver iron content and a higher risk of Parkinson's disease (PD). These findings suggest that interventions targeting body iron metabolism, particularly liver iron levels, may be effective in preventing PD. [ABSTRACT FROM AUTHOR]

γδ T cells facilitate the CD4+ T helper 1 (Th1) cell response against Plasmodium infection by activating conventional dendritic cells (cDCs), although the underlying mechanism remains elusive. Our study revealed that γδ T cells promote the complete maturation and production of interleukin-12 and CXCR3-ligands specifically in type 1 cDCs (cDC1), with minimal impact on cDC2 and monocyte derived DCs (Mo-DCs). During the initial infection phase, γδ T cell activation and temporal accumulation in the splenic white pulp, alongside cDC1, occur via CCR7-signaling. Furthermore, cDC1/γδ T cell interactions in the white pulp are amplified through CXCR3 signaling in γδ T cells, optimizing Th1 cell priming by cDC1. We also demonstrated how transitional Th1 cells arise in the white pulp before establishing their presence in the red pulp as fully differentiated Th1 cells. Additionally, we elucidate the reciprocal activation between γδ T cells and cDC1s. These findings suggest that Th1 cell priming is orchestrated by this reciprocal activation in the splenic white pulp during the early phase of blood-stage Plasmodium infection. [ABSTRACT FROM AUTHOR]

Background: Prediabetes mellitus (PreDM) is a high-risk state for developing type 2 diabetes mellitus (T2DM) and often goes undiagnosed, which is closely associated with obesity and characterized by insulin resistance that urgently needs to be treated. Purpose: To obtain a better understanding of the biological processes associated with both "spleen-dampness" syndrome individuals and those with dysglycaemic control at its earliest stages, we performed a detailed metabolomic analysis of individuals with various early impairments in glycaemic control, the results can facilitate clinicians' decision making and benefit individuals at risk. Methods: According to the diagnostic criteria of TCM patterns and PreDM, patients were divided into 4 groups with 20 cases, patients with syndrome of spleen deficiency with dampness encumbrance and PreDM (PDMPXSK group), patients with syndrome of dampness-heat in the spleen and PreDM (PDMSRYP group), patients with syndrome of spleen deficiency with dampness encumbrance and normal blood glucose (NDMPXSK group), and patients with syndrome of dampness-heat in the spleen and normal blood glucose (NDMSRYP group). Plasma samples from patients were collected for clinical index assessment and untargeted metabolomics using liquid chromatography-mass spectrometry. Results: Among patients with the syndrome of spleen deficiency with dampness encumbrance (PXSK), those with PreDM (PDMPXSK group) had elevated levels of 2-hour post-load blood glucose (2-h PG), glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure (SBP) than those in the normal blood glucose group (NDMPXSK group, P < 0.01). Among patients with the syndrome of dampness-heat in the spleen (SRYP), the levels of body mass index (BMI), fasting blood glucose (FBG), 2-h PG, HbA1c, and fasting insulin (FINS) were higher in the PreDM group (PDMSRYP group) than those in the normal blood glucose group (NDMSRYP group, P < 0.05). In both TCM syndromes, the plasma metabolomic profiles of PreDM patients were mainly discriminatory from the normal blood glucose controls of the same syndrome in the levels of lipid species, with the PXSK syndrome showing a more pronounced and broader spectrum of alterations than the SRYP syndrome. Changes associated with PreDM common to both syndromes included elevations in the levels of 27 metabolites which were mainly lipid species encompassing glycerophospholipids (GPs), diglycerides (DGs) and triglycerides (TGs), cholesterol and derivatives, and decreases in 5 metabolites consisting 1 DG, 1 TG, 2 N,N-dimethyl phosphatidylethanolamine (PE-NMe2) and iminoacetic acid. Correlation analysis identified significant positive correlations of 3α,7α,12α,25-Tetrahydroxy-5β-cholestane-24-one with more than one glycaemia-related indicators, whereas DG (20:4/20:5) and PC (20:3/14:0) were positively and PC (18:1/14:0) was inversely correlated with more than one lipid profile-related indicators. Based on the value of correlation coefficient, the top three correlative pairs were TG with PC (18:1/14:0) (r = − 0.528), TG with TG (14:0/22:4/22:5) (r = 0.521) and FINS with PE-NMe (15:0/22:4) (r = 0.52). Conclusion: Our results revealed PreDM patients with different TCM syndromes were characterized by different clinical profiles. Common metabolite markers associated with PreDM shared by the two TCM syndromes were mainly lipid species encompassing GP, GL, cholesterol and derivatives. Our findings were in line with the current view that altered lipid metabolism is a conserved and early event of dysglycaemia. Our study also implied the possible involvement of perturbed bile acid homeostasis and dysregulated PE methylation during development of dysglycaemia. [ABSTRACT FROM AUTHOR]

Live attenuated vaccines (LAVs) whose virulence would be controlled at the tissue level could be a crucial tool to effectively fight intracellular bacterial pathogens, because they would optimize the induction of protective immune memory while avoiding the long-term persistence of vaccine strains in the host. Rational development of these new LAVs implies developing an exhaustive map of the bacterial virulence genes according to the host organs implicated. We report here the use of transposon sequencing to compare the bacterial genes involved in the multiplication of Brucella melitensis, a major causative agent of brucellosis, in the lungs and spleens of C57BL/6 infected mice. We found 257 and 135 genes predicted to be essential for B. melitensis multiplication in the spleen and lung, respectively, with 87 genes common to both organs. We selected genes whose deletion is predicted to produce moderate or severe attenuation in the spleen, the main known reservoir of Brucella, and compared deletion mutants for these genes for their ability to protect mice against challenge with a virulent strain of B. melitensis. The protective efficacy of a deletion mutant for the plsC gene, implicated in phospholipid biosynthesis, is similar to that of the reference Rev.1 vaccine but with a shorter persistence in the spleen. Our results demonstrate that B. melitensis faces different selective pressures depending on the organ and underscore the effectiveness of functional genome mapping for the design of new safer LAV candidates. Author summary: Brucellosis is one of the most widespread bacterial zoonoses worldwide. We report here the use of transposon sequencing to compare the bacterial genes involved in the multiplication of Brucella melitensis, a major causative agent of brucellosis, in the lungs and spleens of infected mice. We found 257 and 135 genes predicted to be essential for B. melitensis multiplication in the spleen and lung, respectively, with 87 genes common to both organs, which demonstrates that B. melitensis faces different selective pressures depending on the organ. Then, we selected genes whose deletion is predicted to produce moderate or severe attenuation in the spleen, the main known reservoir of Brucella, and compared deletion mutants for these genes for their ability to protect mice against challenge with a virulent strain of B. melitensis. We observed that the protective efficacy of a deletion mutant for the plsC gene, implicated in phospholipid biosynthesis, is similar to that of the reference Rev.1 vaccine but with a shorter persistence in the spleen. Our results demonstrate the effectiveness of functional genome mapping for the design of new safer live attenuated vaccine candidates. [ABSTRACT FROM AUTHOR]

Background: Infection with the filarial nematode Loa loa, endemic in Central and Western Africa, has been associated with increased morbidity and mortality. A number of reports described the presence of spleen nodules, originating from degenerating microfilariae, in humans and animals infected with L. loa. The long-term consequences of this process on individuals chronically exposed to infection in terms of spleen function and possible link with excess mortality are unknown. The aim of this study was to evaluate the prevalence of focal spleen lesions, their evolution over time, and markers of spleen function, in individuals with L. loa infection living in highly endemic areas of Gabon. Methodology/principal findings: This was a cross-sectional study followed by a longitudinal study of the subset of individuals with spleen nodules. Two hundred sixteen participants from Ngounié and Moyen-Ogooué provinces of Gabon, reporting a history of eyeworm migration and/or Calabar swelling, were included. Participants were categorized into infected microfilaraemic with low (N = 74) and high (N = 10) microfilaraemia, and symptomatic amicrofilaraemic (N = 132), based on blood microscopy. Howell-Jolly bodies in erythrocytes, as indirect marker of spleen functional impairment, were within normal ranges. On ultrasound, no evident signs of spleen fibrosis or hypotrophy were observed. Multiple spleen hypoechoic centimetric macronodules were observed in 3/216 participants (1.4%), all with microfilaraemic L. loa infection (3.4% of microfilaraemics); macrondules disappeared at the 6-months follow-up examination in 2/3 individuals. Spleen hypoechoic micronodules, persisting at the 6-months follow-up, were detected in 3/216 participants (1.4%), who were all amicrofilaraemic. Conclusions/significance: Transitory spleen macronodules are present in a small but consistent proportion of individuals with microfilaraemic loiasis, appearing a rather benign phenomenon in terms of impact on spleen morphology and function. Their occurrence should be taken into consideration to avoid misdiagnosis and mistreatment. Prevalence and significance of spleen micronodular ultrasound patterns in the general population would be also worth evaluating. Author summary: Loa loa is a vector borne, filarial worm affecting an estimated 20 million people in Central and West Africa. Long considered a benign infection, more recently it has been associated with substantial morbidity and increased mortality in individuals with high L. loa microfilaraemia, prompted to reconsider the importance this infection and investigate the potential pathophysiological mechanisms. The spleen has a central role in the response to pathogens, including parasites; therefore, its dysfunction may lead to an increase in the risk and severity of infectious diseases, which might contribute to the observed excess mortality in hypermicrofilaremic loiasis. The presence of spleen centimetric nodules, originating from degradation of microfilariae, in humans and animals infected with L. loa, has been described, but the long-term consequences of this process on individuals chronically exposed to infection in terms of spleen function are unknown. In this study performed in individuals with L. loa infection living in highly endemic areas of Gabon, we found a prevalence of 3.4% spleen nodules in microfilaraemic participants, while no such lesions were observed in symptomatic amicrofilaraemic participants. Nodules were transitory and appeared to be a rather benign phenomenon in terms of impact on spleen morphology and function. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to clarify surgical complications associated with open surgery for congenital diaphragmatic hernia (CDH). Methods: We performed an exploratory data analysis of the clinical characteristics of surgical complications of neonates with CDH who underwent laparotomy or thoracotomy between 2006 and 2021. Data of these patients were obtained from the database of the Japanese CDH Study Group. Results: Among 1,111 neonates with left or right CDH, 852 underwent open surgery (laparotomy or thoracotomy). Of these 852 neonates, 51 had the following surgical complications: organ injury (n = 48; 6% of open surgeries); circulatory failure caused by changes in the organ location (n = 2); and skin burns (n = 1). Injured organs included the spleen (n = 30; 62% of organ injuries), liver (n = 7), lungs (n = 4), intestine (n = 4), adrenal gland (n = 2), and thoracic wall (n = 2). Fourteen of the patients who experienced organ injury required a blood transfusion (2% of open surgeries). The adjusted odds ratio of splenic injury for patients with non-direct closure of the diaphragm was 2.2 (95% confidence interval, 1.1–4.9). Conclusion: Of the patients who underwent open surgery for CDH, 2% experienced organ injury that required a blood transfusion. Non-direct closure of the diaphragmatic defect was a risk factor for splenic injury. [ABSTRACT FROM AUTHOR]

AbstractPhillinus gilvus (Schwein.) Pat has pharmacological effects such as tonifying the spleen, dispelling dampness, and strengthening the stomach, in which sterol is one of the main compounds of P. gilvus, but there has not been thought you to its extraction and detailed identification of its composition, in the present study, we used artificial neural network (ANN) and response surface methodology (RSM) to optimize the conditions of ultrasonic-assisted extraction, and the parameters of the independent and interaction effects were evaluated. Ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to identify the major components in the purified extract. The results showed that the optimal extraction process conditions were: ultrasonic time 96 min, ultrasonic power 140 W, liquid to material ratio 1:25 g/ml, and ultrasonic temperature 30.7 °C. The compliance rates of the predicted and experimental values for the artificial neural network model and the response surface model were 98.3% and 96.12%, respectively, indicating that both models have the potential to be used for optimizing the extraction process of P. gilvus in industry. A total of 120 compounds and 30 major steroids were identified by comparison with the reference compounds. Among the major steroidal components are these findings will contribute to the isolation and utilization of active ingredients in P. gilvus. [ABSTRACT FROM AUTHOR]

To investigate the protective effect of selenated Acanthopanax polysaccharide (Se-ASPS) against D-galactose-induced (D-gal) oxidative damage in mice. The oxidative damage model of mice was established by intrabitoneal injection of D-gal. The mice in the high, medium and low dose groups were supplemented with 200, 100 and 50 mg/kg·bw of selenated Acanthopanax polysaccharide, respectively. The mice were gavaged continuous intragastric administration for 28 days. Changes in body weight and feed intake and organ indices of mice in each group were compared, and HE staining was used to observe liver lesions in mice. Serum, heart, liver, spleen and kidney tissues were analyzed for SOD, CAT, GSH-Px, MDA, AST, ALT using the kit. Compared with the D-gal model group, both selenated Acanthopanax polysaccharide groups significantly increased the body weights of mice (P<0.05), and the selenated Acanthopanax polysaccharide highdose group significantly increased the organ index of mice (P<0.05). HE staining revealed that selenated Acanthopanax polysaccharide could repair the damage caused by D-galactose to mouse liver tissue. The high-dose group of selenated Acanthopanax polysaccharides significantly increased the activities of SOD, GSH-Px, and CAT enzymes in serum, heart, liver, spleen, and kidney tissues of mice (P<0.05), and significantly decreased the contents of MDA, AST, and ALT (P<0.05), with the high-dose group showing the most prominent performance (P<0.01). Se-ASPS can significantly protect the organism against oxidative damage caused by D-gal. [ABSTRACT FROM AUTHOR]

In Internal Radiotherapy, radiopharmaceutical dosimetry provides an accurate estimation of absorbed radiation doses to organs at risk and tumours. In this paper Velocity Theranostics (Varian Medical Systems), is investigated. Its performances are compared to OLINDA 2.0 in both an anthropomorphic phantom and a group of patients. Velocity Theranostics was evaluated with a cohort of patients (15) treated with 177Lu radiolabelled peptides. The absorbed doses were calculated for the liver, spleen and kidneys, separately with OLINDA 2.0 and Velocity Theranostics using the same set of images. To reduce the contribution of Time-integrated activities (TIAs) on the results and to merely compare the dose calculation algorithms, the OLINDA 2.0 absorbed doses were calculated using the TIA values calculated in Velocity Theranostics. The absorbed doses from Velocity Theranostics were found to be correlated with the doses from OLINDA 2.0 with the TIAs from Theranostics (Lin's coefficient = 0.894 and R2 = 0.9531). Absorbed doses from Velocity Theranostics are reliable at least as reliable as those for OLINDA 2.0, with many advantages regarding accuracy of calculations and robustness. In conclusion, the personalisation of dosimetry may be totally fulfilled by computational systems for absorbed dose in internal radiotherapy, equipped with a complete workflow and borrowed from external radiotherapy. [ABSTRACT FROM AUTHOR]

Single B-cell antibody generation technology is an advanced method that offers several advantages, including rapid production, high efficiency, and high yield. The antibodies generated via this technique retain their natural conformation and are well suited for applications in pathogen diagnosis, disease treatment, and investigations of virus cross-species transmission mechanisms. Our study aimed to establish a platform for generating single B-cell antibodies specifically targeting the foot-and-mouth disease virus (FMDV) 146S antigen in mice. Female BALB/c mice were immunized with inactivated O-type FMDV 146S antigen, and spleen cells were collected for further analysis. Flow cytometric sorting was performed using a biotin-labeled O-type FMDV 146S antigen as a decoy to identify and select CD19 + /CD21/35 + /CD43-/IgM-/Biotin + antigen-specific individual B cells. The gene sequences encoding the variable regions of the heavy and light chains of the murine IgG antibodies were obtained via single-cell nested PCR amplification. Separate constructs were created for the heavy and light chain plasmids to ensure the proper expression of intact IgG antibodies. These plasmids were cotransfected into human embryonic kidney 293T (HEK293T) cells, leading to the successful production and purification of 15 specific monoclonal antibodies (mAbs), 10 which exhibited activity in ELISA tests, and six antibodies that displayed activity in IFA tests. These findings highlight the successful development of a method for generating mouse-derived single B-cell antibodies that target FMDV. This achievement provides a solid foundation for diagnostic techniques and the analysis of antigenic structural variations. [ABSTRACT FROM AUTHOR]

Background The largest and most significant lymphatic organ in the human body is the spleen. These days, its hematological and immunological actions are fully appreciated. The shape of the spleen varies from a slightly curved wedge to a domed tetrahedron. The size and weight of the spleen vary with age. Methods The present study was conducted on 65 human spleens after getting the ethical clearance. Specimens were collected depending on the availability of cadavers or unclaimed autopsy bodies. The morphological features of the spleen like its length, breadth, width and weight were measured. The shape, poles, borders, surfaces, notches and the impressions on the spleen were observed. Accessory splenic tissues, if they were present, were noted. The sample size was calculated using mobile app nCalculator Application. Results Out of 65 spleens, 40(61.54%), 14 (21.53%), 8(12.61%), 2 (3.08%) 1(1.50%) were wedge, tetrahedral, triangular, oval and irregular in shape respectively. Most of the spleens had weights in the range of 80 to 300 gm, the lengths varied between 7.4 cm and 14.3 cm, the breadth varied between 3.3 cm and 9.9 cm, the widths varied from 2 cm to 8 cm. In all the spleens two poles, two borders and two surfaces were observed. In 54(83.08%) specimens, splenic notches were found on the superior border but in 11(16. 92%) on the inferior border. Accessory spleen was found in 6(9.23%) specimens. Conclusions The findings of the present study will be fundamental importance to the physicians, surgeons and radiologists and of course, this knowledge is very important for the anatomists during their routine classroom dissections. [ABSTRACT FROM AUTHOR]

Objective: To establish a mice model that is more in line with the human immunocompromised state, and to investigate the regulatory effect of Rosa laevigata Michx., probiotics and their combination on their immune function. Methods: Immunosuppressive model of mice was established by using cyclophosphamide with different dosage, time and end point, and compared with immunosuppressive model induced by hydrocortisone and cyclosporine A, immunosuppressive model of mice was established by injecting 25 mg/kg cyclophosphamide 7 times every other day, without recovery period; changes in the proportion of lymphocytes in spleen （CD4+T cells, CD8+T cells, CD19+B cells） were analyzed by flow cytometry; qRT-PCR was used to detect expression levels of inflammatory factors （IL-1β and IL-6） mRNA in spleen. Results: After continuous injection of 80 mg/kg cyclophosphamide for 3 days, the thymus was atrophied, the spleen was significantly swelling, proportion of immune cells CD4+T cells, CD8+T cells and CD19+B cells in spleen were significantly decreased, while mRNA expressions of IL-1β and IL-6 were up-regulated. After 7 injections of 25 mg/kg cyclophosphamide every other day, the thymus and the spleen were significantly atrophied, proportion of CD4+T cells and CD8+T cells in spleen showed an increasing trend, and mRNA expressions of IL-1β and IL-6 were up-regulated; after 1 week or 2 weeks recovery period from cyclophosphamide injection, weight and index of immune organs, proportion of spleen lymphocytes and mRNA expressions of inflammatory cytokines in spleen were significantly reversed; Rosa laevigata Michx. combined with probiotics could significantly reverse the up-regulation of CD4+T cells and inflammatory factor IL-1β caused by cyclophosphamide. Conclusion: In this study, an immunocompromised mice model has been established with 7 injections of 25 mg/kg cyclophosphamide every other day and without recovery period. And a certain positive immunomodulatory effect of the combination of Rosa laevigata Michx. and probiotics has been found. [ABSTRACT FROM AUTHOR]

Wandering spleen (WS) is a rare condition where the spleen is abnormally mobile due to lax or poorly developed ligaments, leading to complications like torsion and laceration after trauma. We describe a case of a 31-year-old postpartum female who presented with severe abdominal pain following blunt trauma. Diagnostics showed an enlarged, ectopic spleen, and significant hematoma. Surgical exploration revealed a 10-cm splenic laceration, necessitating a splenectomy due to extensive blood loss and organ damage. This case highlights the challenges of diagnosing WS, particularly in postpartum patients with increased ligamentous laxity, emphasizing the need for vigilant monitoring and potentially preventive surgical measures to manage this complex condition effectively. [ABSTRACT FROM AUTHOR]

Probiotics are well-known to be directly or indirectly involved in the host immune system. In this study, we analyzed the immune-boosting effects of lactic acid bacteria, including Limosilactobacillus and Lactococcus, in immunocompetent C57BL/6J mice. Three different lactic acid bacteria strains were orally administered to C57BL/6J mice for 8 weeks. Then, liver, spleen, and whole blood were harvested after sacrificing the animals. There were no significant changes in whole-body weight, weight of organs, or complete blood cell count by oral administration of lactic acid bacteria. The frequencies of CD3+, CD4+, and CD8+ T cells were significantly increased in the Limosilactobacillus reuteri MG5462 group compared to control. The frequency of NK1.1+ cells was significantly increased in the Lactococcus lactis MG5474 group compared to control. On the other hand, splenocyte proliferations and natural killer cytotoxicity did not differ between groups. In addition, the MG5462 group had a significant increase in the production of TNF-α compared to the control, which is consistent with the upregulation of T cells in the MG5462 group. Therefore, Limosilactobacillus reuteri could be a functional food additive to boost immunity by positively affecting T cell populations. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) continues to spread in Africa, Europe, Asia and the island of Hispaniola, increasing the need to develop more streamlined and highly efficient surveillance and diagnostic capabilities. One way to achieve this is by further optimization of already established standard operating procedures to remove bottlenecks for high-throughput screening. Real-time polymerase chain reaction (real-time PCR) is the most sensitive and specific assay available for the early detection of the ASF virus (ASFV) genome, but it requires high-quality nucleic acid extracted from the samples. Whole blood from live pigs and spleen tissue from dead pigs are the preferred samples for real-time PCR. Whole blood can be used as is in nucleic acid extractions, but spleen tissues require an additional homogenization step. In this study, we compared the homogenates and swabs prepared from 52 spleen samples collected from pigs experimentally inoculated with highly and moderately virulent ASF virus strains. The results show that not only are the spleen swabs more sensitive when executed with a low-cell-count nucleic acid extraction procedure followed by real-time PCR assays but they also increase the ability to isolate ASFV from positive spleen samples. Swabbing is a convenient, simpler and less time-consuming alternative to tissue homogenization. Hence, we recommend spleen swabs over tissue homogenates for high-throughput detection of ASFV by real-time PCR. [ABSTRACT FROM AUTHOR]

Background: Preserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons' decision-making. Methods: In this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions. Results: After manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3). Conclusion: Continuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The Baveno VI criteria have set the stage for noninvasive assessment of compensated advanced chronic liver disease (ACLD). The algorithm combining liver stiffness measurement (LSM, <20 kPa) and platelet count (>150,000/µL) safely avoids screening endoscopy for varices needing treatment (VNT) but identifies only a relatively low number of patients. We aimed to evaluate the value of spleen stiffness measurement (SSM) using spleen-dedicated elastography in ruling out VNT. METHODS: In this real-life multicenter retrospective derivation-validation cohort, all consecutive patients with ACLD (defined by LSM ≥10 kPa) with available upper endoscopy, laboratory results, spleen diameter, LSM, and SSM measured with spleen-dedicated transient elastography were included. VNT were defined as medium-to-large varices or small varices with red spots. RESULTS: In the derivation cohort (n = 201, 11.9% VNT), SSM demonstrated excellent capability at identifying VNT (area under the receiver operating characteristic curve [AUROC] 0.88), outperforming LSM (AUROC 0.77, P = 0.03) and platelets (AUROC 0.73, P = 0.002). In comparison with Baveno VI criteria (33.8% spared endoscopies), the sequential Baveno VI plus SSM and a novel spleen size and stiffness model were able to increase the number of patients avoiding endoscopy (66.2% and 71.1%, respectively) without missing more than 5% of VNT. These findings were confirmed in an external validation cohort of patients with more advanced liver disease (n = 176, 34.7% VNT) in which the number of spared endoscopies tripled (27.3% and 31.3% for SSM-based algorithms) compared with Baveno VI criteria (8.5%). DISCUSSION: Spleen stiffness-based algorithms are superior to Baveno VI criteria in ruling out VNT in patients with ACLD and double the number of patients avoiding screening endoscopy. [ABSTRACT FROM AUTHOR]

Administration of oxygen microbubbles (OMBs) has been shown to increase oxygen and decrease carbon dioxide in systemic circulation, as well as reduce lung inflammation and promote survival in preclinical models of hypoxia caused by lung injury. However, their impact on microenvironmental oxygenation remains unexplored. Herein, we investigated the effects of intraperitoneal administration of OMBs in anesthetized rats exposed to hypoxic ventilation (FiO2 = 0.14). Blood oxygenation and hemodynamics were evaluated over a 2 h time frame, and then organ and tissue samples were collected for hypoxic and metabolic analyses. Data showed that OMBs improved blood SaO2 (~14%) and alleviated tissue hypoxia within the microenvironment of the kidney and intestine at 2 h of hypoxia. Metabolomic analysis revealed OMBs induced metabolic differences in the cecum, liver, kidney, heart, red blood cells and plasma. Within the spleen and lung, principal component analysis showed a metabolic phenotype more comparable to the normoxic group than the hypoxic group. In the spleen, this shift was characterized by reduced levels of fatty acids and 2-hydroxygluterate, alongside increased expression of antioxidant enzymes such as glutathione and hypoxanthine. Interestingly, there was also a shuttle effect within the metabolism of the spleen from the tricarboxylic acid cycle to the glycolysis and pentose phosphate pathways. In the lung, metabolomic analysis revealed upregulation of phosphatidylethanolamine and phosphatidylcholine synthesis, indicating a potential indirect mechanism through which OMB administration may improve lung surfactant secretion and prevent alveolar collapse. In addition, cell-protective purine salvage was increased within the lung. In summary, oxygenation with intraperitoneal OMBs improves systemic blood and local tissue oxygenation, thereby shifting metabolomic profiles of the lung and spleen toward a healthier normoxic state. [ABSTRACT FROM AUTHOR]

Splenic vein aneurysm (SVA) rupture is a rare clinical entity, with few case reports detailing its occurrence during pregnancy. We describe a case of a SVA rupture and present a systematic review of the literature in relation to splenic vein rupture, with or without aneurysm. Our case was of a 30‐year‐old woman, Para 4 at 37 weeks' gestation who presented with significant abdominal pain and subsequent maternal collapse. Massive intra‐abdominal hemorrhage was identified, with splenic vessel rupture suspected. A splenectomy and partial pancreatectomy were performed along with massive blood product transfusion. There was both maternal and fetal survival with no long‐term sequelae at follow‐up. Histological examination of the spleen and its vessels noted a SVA rupture. In a subsequent systematic review of the literature, we identified 10 cases of splenic vein rupture with only two previously documented cases of SVA rupture in pregnancy. Maternal and fetal survival has only been reported in two cases of splenic vein rupture, with ours being a third. [ABSTRACT FROM AUTHOR]

The spleen has an essential role in immune responses regulation and is considered the biggest peripheral immune organ. Citicoline is used for various brain disorders management. This study aimed to examine the using possibility of citicoline to treat γ-radiation-induced splenic inflammation in rats. Eighteen male albino rats were classified into: Group 1 (control) animals were kept as control. Group 2 (γ-radiation) animals were total-body γ-irradiated with 6 Gy. Group 3 (γ-radiation + citicoline) rats were γ-irradiated with 6 Gy, then injected intraperitoneally with citicoline (300 mg/kg/d) 5 min after irradiation for one week. Levels of TNF-α, IL-1β, iNOS, NF-κB, JAK2, and STAT3 were determined in spleen tissue, along with histopathological examination. Rats exposure to gamma-radiation led to elevation in splenic TNF-α, IL-1β, NF-κB, iNOS, JAK2, and STAT3 levels significantly. Treatment with citicoline after gamma-radiation exposure improved this elevation, and modulated gamma-radiation-induced histopathological alterations. This data showed that citicoline inhibited γ-radiation-induced splenic inflammation via suppressing NF-κB and JAK2/STAT3 signaling pathways in spleen tissue. [ABSTRACT FROM AUTHOR]

Objectives: Splenic lesions might exhibit overlapping imaging features, varying from benign entities like cysts and hemangiomas to malignancies such as lymphoma and angiosarcoma. This meta-analysis aims to delineate imaging characteristics that distinguish malignant from benign splenic lesions. Methods: Adhering to PRISMA guidelines, we searched PubMed, Scopus, and Web of Science for studies on imaging features differentiating malignant from benign splenic lesions. We extracted data on splenic pathology and imaging characteristics and assessed the methodological quality via QUADAS-2. Odds ratio meta-analyses were performed using STATA (Version 17.0, Stata Corp, College Station, TX). Results: Portal phase hypoenhancement, hypovascular enhancement pattern, diffusion restriction, and late phase hypoenhancement, with odds ratios above 10, highly indicate malignancy. Other features suggestive of malignancy include solid morphology, lymphadenopathy, presence of perisplenic fluid, arterial hypoenhancement, hypoechogenicity on ultrasound, splenomegaly, and presence of multiple lesions. In contrast, cystic morphology, hypervascular-washout and hypervascular-persistent pattern of enhancement, late phase hyperenhancement, anechogenicity on ultrasound, portal phase hyperenhancement, well-defined borders, and calcification are in favour of benign pathology. Conclusion: The study underscores the critical role of contrast-enhanced and diffusion-weighted imaging in distinguishing malignant from benign splenic lesions, emphasizing the role of features like portal phase hypoenhancement and restricted diffusion in diagnosing malignancies. Additionally, the study emphasizes the value of contrast-enhanced ultrasound, which allows for the visualization of key contrast-enhancement patterns without the risk of ionizing radiation exposure. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and effectiveness of percutaneous transsplenic access (PTSA) for portal vein (PV) interventions among patients with PV disease. Materials and methods: Adult patients with PV disease were enrolled if they required percutaneous catheterization for PV angioplasty, embolization, thrombectomy, variceal embolization, or transjugular intrahepatic portosystemic shunt (TIPS) placement for a difficult TIPS or recanalization of a chronically occluded PV. The procedures were performed between January 2018 and January 2023. Patients were excluded if they had an active infection, had a chronically occluded splenic vein malignant infiltration of the needle tract, had undergone splenectomy, or were under age 18 years. Results: Thirty patients (15 women, 15 men) were enrolled. Catheterization of the PV through PTSA succeeded for 29 of 30 patients (96.7%). The main adverse effect recorded was flank pain in 5 of 30 cases (16.7%). No bleeding events from the spleen, splenic vein, or percutaneous access point were recorded. Two cases (6.7%) each of hepatic bleeding and rethrombosis of the PV were reported, and a change in hemoglobin levels (mean [SD], − 0.5 [1.4] g/dL) was documented in 14 cases (46.7%). Conclusion: PTSA as an approach to accessing the PV is secure and achievable, with minimal risk of complications. Minimal to no bleeding is possible by using tract closure methods. [ABSTRACT FROM AUTHOR]

Non-cutaneous extranodal mature T- and natural killer (NK)-cell neoplasms represent a broad spectrum of neoplasms involving various extranodal sites, predominantly in the liver, spleen, bone marrow, gastrointestinal tract, and nasal cavity, ranging from indolent to highly aggressive diseases. Extranodal NK/T-cell lymphoma (ENKTL), aggressive NK-cell leukaemia (ANKL), and EBV-positive T-cell and NK-cell lymphoid proliferations and lymphomas of childhood, are strongly associated with Epstein-Barr virus (EBV). Overlapping clinical and histopathological features exist between entities, making differentiation challenging. A multidisciplinary approach is essential in establishing the correct diagnosis. Recent advances in genomics have provided new insights into the pathogenesis, aided in the diagnosis, prognostication, and identification of potential therapeutic targets. This article focuses on the clinicopathologic features of these entities, incorporating recent advances in genetic characterization, and highlighting features that assist in distinguishing these conditions from potential mimickers. [ABSTRACT FROM AUTHOR]

Bovine casein (CN) is abundant in cow milk (CM) and is a major allergen in CM. Recently, several studies have investigated the allergenicity of CN in vivo and in vitro. In this study, the potential antigenicity of enzymatically hydrolyzed CN in vitro was evaluated, and the results showed that Alcalase hydrolysis remarkably reduced the IgG-binding capacity of CN by 36.22–77.84%. Additionally, the IgE-binding capacity of CN was reduced by Alcalase (65.29%) and Protamex (68.49%) treatments. The allergenicity of CN in vivo was also assessed, and the results showed that the allergic symptoms of BALB/c mice were effectively relieved; the levels of IgG, IgE, mMCP-1, histamine, and Th2-related cytokines were reduced; and allergic inflammation of the lungs, jejunum, and spleen was significantly alleviated. These findings suggest that Alcalase, Protamex, and Flavourzyme hydrolysis could effectively reduce sensitization to CN, and our research provides a foundation for developing hypoallergenic dairy products. [ABSTRACT FROM AUTHOR]

Background Methods Key Results Conclusions and Inferences The traditional herbal medicine Atractylodes macrocephala Koidz. (A. macrocephala) is commonly utilized for alleviating symptoms associated with spleen deficiency, abdominal distension, diarrhea, and constipation. These pharmacological effects are attributed to a variety of active constituents. However, the specific bioactive compounds responsible for promoting defecation and gastrointestinal transit in A. macrocephala remain unidentified.The primary polysaccharide characteristics of PAMK was elucidated by HPLC, FT‐IR, and HGPGC. Efficacy of PAMK (0.07, 0.14, and 0.28 mg/g) on mice was evaluated in a spleen deficiency constipation mouse model by analyzing stool parameters, constipation‐related physiological indexes, and SCFAs. The expression levels of 5‐HT3R, 5‐HT4R, and related receptor genes were examined by RT‐qPCR, and neurotransmitters were examined using ELISA. Finally, the diversity of gut microbiota was analyzed with 16S rDNA sequencing.The results showed that PAMK significantly reduced the gastrointestinal transport time and increased the number of fecal pellets and fecal water content in spleen deficiency constipation model mice. PAMK kept the balance of 5‐HT, SCFAs, TPH‐1, SERT, CgA, and neurotransmitter levels (VIP, SP, MTL) in mice colon. In addition, PAMK could regulate the abundance of gut microbiota such as Alistopes, Bacteroides, and Odoribacter in spleen deficiency constipation model mice gut.It can be concluded that PAMK effectively ameliorated the symptoms of spleen deficiency constipation in mice by modulating the expression of 5‐HT and its associated receptors. The underlying mechanism was elucidated, providing a solid theoretical foundation for the therapeutic application of A. macrocephala in treating spleen deficiency constipation and offering potential for developing novel approaches to address this condition. [ABSTRACT FROM AUTHOR]

Background: Brain inflammation plays a key role in ischemia/reperfusion (I/R) injury and is the main cause of "ineffective or futile recanalization" after successful mechanical thrombectomy (MT) in acute ischemic stroke (AIS). One of the primary sources of inflammatory cells after AIS are derived from the spleen. As an innovative and potential neuroprotective strategy after stroke, Remote Administration of Hypothermia (RAH) temporarily suppresses immune activities in the spleen, reduces the release of inflammatory cells and cytokines into blood, and thus reversibly diminishes inflammatory injury in the brain. Methods: This single-center, prospective, randomized controlled study (RCT) is proposed for AIS patients with anterior circulation large vessel occlusion (LVO). Subjects will be randomly assigned to either the control or intervention groups in a 1:1 ratio (n = 40). Participants allocated to the intervention group will receive RAH on the abdomen above the spleen prior to recanalization until 6 h after thrombectomy. All enrolled patients will receive standard stroke Guideline care. The main adverse events associated with RAH are focal cold intolerance and abdominal pain. The primary outcome will assess safety as it pertains to RAH application. The secondary outcomes include the efficacy of RAH on spleen, determined by spleen volumes, blood inflammatory factor (cells and cytokines), and on brain injury, determined by infarction volumes and poststroke functional outcomes. Discussion: This study aims to examine the safety and preliminary effectiveness of RAH over the spleen during endovascular therapy in AIS patients. The results of this study are expected to facilitate larger randomized clinical trials and hopefully prove RAH administration confers adjuvant neuroprotective properties in AIS treated with MT. [ABSTRACT FROM AUTHOR]

The liver is essential for nutritional balance in fish, and liver damage in farmed fish often arises from factors like overfeeding, causing various health issues. Clinical observations indicate that liver diseases frequently involve spleen dysfunction, and there is evidence to suggest that the spleen has a significant impact on liver function. However, there has been no discussion on the role of the spleen in maintaining liver health in fish. To understand the role of fish spleen in liver metabolism, this study selected Nile tilapia (Oreochromis niloticus) as the experimental material and first established a tilapia splenectomy model. Various biochemical parameters of the liver and serum were measured, and the liver metabolism characteristics of the splenectomy group (SP group) and the sham operation group (SO group) were analyzed using metabolomics. After splenectomy, biochemical parameters of the liver and serum showed abnormalities, including significant increases in total cholesterol (T-CHO) and serum total bile acid (TBA) levels, alongside a significant decrease in liver TBA levels, suggesting impaired metabolic function and cholesterol deposition in the liver. Metabolomics analysis showed that metabolites such as lipids, lipid-like molecules, and organic acids and derivatives were differentially regulated between the SO and SP group. KEGG analysis showed that differential metabolites were enriched in lipid metabolism and amino acid metabolism. The metabolic pathway analysis of differential metabolites showed that after splenectomy, the low-activity urea cycle in the liver may accelerate lipid synthesis, while low concentrations of aromatic amino acids and taurine may inhibit lipid catabolism. These results indicate that after splenectomy, the liver metabolic capacity is impaired, which causes abnormal lipid metabolism by interfering with amino acid metabolism, making splenectomy tilapia liver at risk of liver disease, including cholesterol deposition, hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our results show that the spleen is involved in regulating liver lipid and amino acid metabolism, and the spleen may interfere with lipid metabolism by regulating liver amino acid metabolism. Our data can provide support for further research on liver and spleen functions and the immune-nutrient metabolism mechanisms in fish, as well as new ideas for healthy fish farming. [ABSTRACT FROM AUTHOR]

Aluminum hydroxide has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. Animals were splitted in 3 treatment groups: vaccine group, adjuvant alone group and control group. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which also allowed isoform-level analysis. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response and cell cycle. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species. [ABSTRACT FROM AUTHOR]

Background: Aging is associated with significant structural and functional changes in the spleen, leading to immunosenescence, yet the detailed effects on splenic vascular endothelial cells (ECs) and their immunomodulatory roles are not fully understood. In this study, a single-cell RNA (scRNA) atlas of EC transcriptomes from young and aged mouse spleens was constructed to reveal age-related molecular changes, including increased inflammation and reduced vascular development and also the potential interaction between splenic endothelial cells and immune cells. Results: Ten clusters of splenic endothelial cells were identified. DEGs analysis across different EC clusters revealed the molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the loss in vascular development function of aged ECs. Notably, four EC clusters with immunological functions were identified, suggesting an Endothelial-to-Immune-like Cell Transition (EndICLT) potentially driven by aging. Pseudotime analysis of the Immunology4 cluster further indicated a possible aging-induced transitional state, potentially initiated by Ctss gene activation. Finally, the effects of aging on cell signaling communication between different EC clusters and immune cells were analyzed. Conclusions: This comprehensive atlas elucidates the complex interplay between ECs and immune cells in the aging spleen, offering new insights into endothelial heterogeneity, reprogramming, and the mechanisms of immunosenescence. [ABSTRACT FROM AUTHOR]

Effects of pulsed electromagnetic fields (PEMF) on immunological factors in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) model were investigated. Hairless mice were randomly assigned to control, acetone and olive oil solution-treated (AOO), PEMF 15 Hz, PEMF 75 Hz, and sham groups (n = 5 each). AOO solution was used to dissolve DNCB. Both PEMF and sham groups were exposed to similar DNCB doses, causing similar AD symptoms. After AD induction for five weeks, only the PEMF groups were exposed to PEMF stimulations (15 Hz, 75 Hz, and 15 mT) inside the solenoid coil, for two weeks. In both groups, splenomegaly was observed, as AD was induced by hyperimmune reactions caused by DNCB sensitization. However, splenomegaly did not occur in the PEMF-exposed groups, and spleen weight decreased similarly to that of the control. Hence, the total splenocytes in the PEMF group were similar to those in the control group, whereas the sham group showed three times the number of splenocytes compared with the PEMF group. The serum immunoglobulin E levels did not significantly change in the PEMF group; however, they increased more than fourfold in the sham group. These results demonstrate that PEMF stimulation ameliorated the abnormal symptoms caused by hyperimmune reactions. [ABSTRACT FROM AUTHOR]

Background: Extraskeletal osteosarcoma is an extremely rare malignancy that accounts for 1% of soft tissue sarcoma and 4.3% of all osteosarcoma. Extraskeletal osteosarcoma can develop in a patient between the ages of 48 and 60 years. The incidence of extraskeletal osteosarcoma is slightly higher in male patients than in females. Case presentation: A 50-year-old Caucasian male patient presented with a 6-month history of intermittent lower-left back pain that limits his activity. Prior ultrasonography and abdominal computed tomography scan showed a diagnosis of kidney stone and tumor in the lower-left abdomen. The computed tomography urography with contrast revealed a mass suspected as a left retroperitoneal malignant tumor. Hence, the tumor was resected through laparotomy and the patient continued with histopathological and immunohistochemistry examination with the result of extraskeletal osteosarcoma. Conclusion: Extraskeletal osteosarcoma presents diagnostic challenges requiring multimodal examination, including histological and immunohistochemistry analyses. This case underscores the aggressive nature and poor prognosis despite undergoing the current suggested treatment. [ABSTRACT FROM AUTHOR]

Since PCV4 was first described in 2019, the virus has been identified in several countries in Southeast Asia and Europe. Most studies have been limited to detecting PCV4 by PCR. Thus, PCV4 has an unclear association with clinical disease. This study utilized 512 porcine clinical lung, feces, spleen, serum, lymphoid tissue, and fetus samples submitted to the ISU-VDL from June–September 2023. PCV4 was detected in 8.6% of samples with an average Ct value of 33. While detection rates among sample types were variable, lymphoid tissue had the highest detection rate (18.7%). Two ORF2 sequences were obtained from lymphoid tissue samples and had 96.36–98.98% nucleotide identity with reference sequences. Direct detection of PCV4 by RNAscope revealed viral replication in B lymphocytes and macrophages in lymph node germinal centers and histiocytic and T lymphocyte infiltration in the lamina propria of the small intestine. PCV4 detection was most commonly observed in nursery to finishing aged pigs displaying respiratory and enteric disease. Coinfection with PCV2, PCV3, and other endemic pathogens was frequently observed, highlighting the complex interplay between different PCVs and their potential roles in disease pathogenesis. This study provides insights into the frequency of detection, tissue distribution, and genetic characteristics of PCV4 in the US. [ABSTRACT FROM AUTHOR]

Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols. [ABSTRACT FROM AUTHOR]

Characteristics of livers and spleens of people with multiple sclerosis (pwMS) could constitute good biomarkers of MS-related characteristics such as the disability status. To test the hypothesis "the gross anatomical features of livers and spleens, are not similar between pwMS with different disease characteristics" a cross-sectional study was conducted on pwMS seen at the Isfahan MS clinic, Iran, from February until December 2023. Definitive, otherwise-healthy, pwMS were enrolled after an initial laboratory evaluation. Presence/absence and grading of non-alcoholic fatty liver disease (NAFLD) and the span of spleen were determined by a radiologist using high-resolution abdominopelvic ultrasonography. 193 pwMS (160 women) were enrolled. Of whom, 143 (74.1%) were receiving first-line disease-modifying therapies (DMTs), 24 (12.4%) fingolimod, and 26 (13.5%) rituximab. The span of spleen was negatively associated with EDSS (adjusted β [SE] − 4.08 [1.52], p < 0.01), as well as 6 m-CDW (adjusted β [SE] − 6.94 [3.56], p = 0.05), unlike age, DMTs, and MS duration (all with p > 0.05). Receiver operating characteristic analysis showed, spleen span performs significant but poor in discrimination of EDSS > 1 from EDSS = 1 (area under curve [AUC] 0.62, SE 0.05, p < 0.01), yet, significant and fair in discrimination of presence from absence of 6 m-CDW (AUC 0.72, SE 0.06, p < 0.01). Other findings were unremarkable. Further longitudinal, prospective studies are warranted to confirm whether smaller spleens are predictive of higher disability accrual rate in pwMS. Particularly, findings require further validation in untreated/treatment-naïve pwMS, and ones with higher EDSS scores. [ABSTRACT FROM AUTHOR]