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Pancreatic endometriosis is an extremely rare condition, with only a few cases described in the literature. Definitive diagnosis is often difficult to elucidate and will almost always require biopsy or surgical resection. We present a case of a female in her early thirties with a well-known history of widespread endometriosis presenting with vague epigastric pain. CT imaging showed an 11 cm well-circumscribed simple-appearing cyst in the lessor sac. Its origin could not be determined preoperatively but it appeared to involve the parenchyma of the body of the pancreas. Due to the associated pain and indeterminate nature, subtotal surgical resection of the extrapancreatic cyst was performed with the intrapancreatic cyst being managed by a cystogastrostomy to the adjacent stomach in a planned pancreas-sparing procedure following intraoperative confirmation it was arising within the pancreas. Pathological evaluation of the resected cyst confirmed it to be an endometrial cyst. The cystogastrostomy anastomosis subsequently obstructed a few weeks postoperatively and symptoms recurred from cyst enlargement. Redo robotic resection with resection of the remnant cyst, cystogastrostomy and en bloc spleen-preserving distal pancreatectomy was performed. The patient had an uneventful recovery. She has had no recurrence of cyst or symptoms since. A procedure video is included in the report.

Giant splenic artery aneurysms are rare and associated with high morbidity and mortality. Early detection is the key to decreasing morbidity and mortality. We present a giant splenic artery aneurysm which was managed by en bloc resection of the spleen, distal pancreas.

Background Non-operative management (NOM) is the standard of care for the majority of children with blunt liver and spleen injuries (BLSI). The shock index pediatric age-adjusted (SIPA) was previously shown to predict the need for blood transfusions in pediatric trauma patients with BLSI. We combined SIPA with base deficit (BD) and International Normalized Ratio (INR) to create the BIS score. We hypothesized that the BIS score would predict the need for blood transfusions and/or failure of NOM in pediatric trauma patients with BLSI. Methods Patients (≤ 18 years) who presented to our Level I pediatric trauma center with BLSI from 2009 to 2019 were identified. BIS scores were calculated by giving 1 point for each of the following: base deficit ≤ -8.8, INR ≥ 1.5, or elevated SIPA. Receiver operating characteristic curves (ROC) were generated for BIS scores ≥ 1, ≥ 2, and ≥ 3. Area under the curve (AUC), sensitivity, and specificity of each score were calculated for ability to predict need for blood transfusions and/or failure of NOM. Results Of 477 children included, 19.9% required a blood transfusion and 6.7% failed NOM. A BIS score ≥ 1 was the best predictor of the need for blood transfusions with an AUC of 0.81 and a sensitivity of 96.0%. A BIS score ≥ 1 was also the best predictor of failure of NOM with an AUC of 0.72 and a sensitivity of 97.0%. Conclusion The BIS score is a highly sensitive tool that identifies pediatric patients with BLSI at risk for blood transfusions and/or failure of NOM. Level of evidence Level III. Type of study Retrospective comparative study.

SUMMARY We present a case of a large splenic pseudocyst in a 16-year-old female, who presented with a left upper quadrant mass and features of gastric outlet obstruction. We discuss the difficulties in diagnosis, the management options and why the definitive treatment of distal pancreatectomy and splenectomy was necessary.

Background Splenectomy is an effective intervention in primary immune thrombocytopenia (ITP). Attempts to define pre-clinical predictors of platelet response to splenectomy are inconsistent. Based on international studies defining the likelihood of platelet response using platelet sequestration, patients with relapsed/refractory ITP being considered for splenectomy at a regional Australian hospital were assessed with 111 Indium-labelled autologous platelet sequestration (ILAPS) studies. Aims To audit the use of ILAPS in an Australian setting and define its role in predicting response to splenectomy. Methods A retrospective review of all patients referred for an ILAPS study at a regional hospital was performed. Results for each patient were expressed as an "R" value (spleen/ liver uptake ratio) to quantify the platelet sequestration pattern and outcome post splenectomy, based on platelet counts. Results A total of 45 patients were identified, 13 underwent splenectomy and 32 were medically managed. Patients with favourable ILAPS scans (pure or predominant splenic sequestration) demonstrated a superior response post splenectomy (100% overall response rate (ORR), 83.5% complete remission (CR)) compared to those with unfavourable ILAPS scans (mixed or pure hepatic sequestration) (71.4% ORR, 57.1% CR) over 12 months. Conclusions The use of ILAPS in the Australian setting is feasible and this experience confirms larger international studies demonstrating its utility as a predictor of response to splenectomy in ITP. An unfavourable ILAPS scan could be considered a negative predictor of response prompting consideration for other emerging ITP treatments such as thrombopoietin-receptor agonists (TPO-RAs) or B-cell depleting therapy such as Rituximab. This article is protected by copyright. All rights reserved.

Ultrasonography (US) is widely used for abdominal imaging. Its noninvasiveness, extensive range of application, and low cost make US a useful and valuable tool for the detection, diagnosis, and follow-up of splenic abnormalities. Concomitantly with the increasing frequency of imaging, more splenic lesions are being discovered and the requirements for the differential diagnosis are rising. In this pictorial essay, we introduce the representative US findings of many different splenic lesions, including normal sonographic findings, normal variants and congenital anomalies, infectious conditions, benign and malignant neoplasms, and non-neoplastic lesions. Knowledge of the US features of various splenic lesions will help narrow the differential diagnosis and guide clinical decision-making.

Antiglycoprotein (anti-GP) antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in the spleen and liver can be studied with 111In-labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration patterns in ITP patients. In this study, we examined the association between antibodies and (1) platelet sequestration site and (2) clearance rate of platelets. All ITP patients receiving an 111In-labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX, and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site, and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed, and 25% a hepatic pattern. In 53% of the patients, anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies. Furthermore, in patients where antibodies were present, the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight into the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease.

Partial splenic embolization (PSE) is a minimally invasive endovascular procedure for the treatment of hypersplenism. This procedure is normally done by catheterization of the splenic artery, which if ligated during surgery, makes the procedure very challenging. We present a case where the splenic artery had been ligated during liver transplant surgery, and the only major endovascular route to reach the spleen was through the hypertrophied tortuous gastroepiploic artery. Successful PSE in these patients suggests the feasibility of this procedure after splenic artery ligation and can thus help to spare a patient from the otherwise more invasive surgical splenectomy.

Aims This study aimed to explore the therapeutic effects of Lactiplantibacillus plantarum HG20 (HG20) on collagen-induced arthritis (CIA) rats and its mechanism. Methods and Results CIA rats were established by injecting bovine type II collagen for 7 days, and treated by intragastric administration HG20 for 21 days. The foot palm temperature and arthritis score were measured once a week. The pathological changes in the knee joint were observed by hematoxylin and eosin staining. The levels of cytokines were detected by enzyme linked immunosorbent assay, and the effects of HG20 on inflammatory and apoptosis pathway of spleen cells were detected by western blot analysis. The results indicated that HG20 reduced the joint swelling degree and foot palm temperature, inhibited the development of joint histopathology, decreased the levels of pro-inflammatory cytokines, down-regulate the expression of pro-inflammatory cytokines by nuclear factor kappa-B pathway, and inhibited the apoptosis of spleen cells by inhibiting phosphatidylinositol 3-kinase/protein kinase B pathway and regulating apoptosis pathways. Conclusions HG20 had an adjuvant therapeutic effect on arthritis in CIA rats, and its mechanism might be related to the inflammatory and apoptosis pathway. Significance and Impact of Study These results revealed that HG20 could be used as a functional probiotic in the field of food and medical, and which played a potential role in the prevention and treatment of arthritis.

Background Biliary atresia (BA) is a rare disorder characterized by obstructive jaundice in infants, shortly after birth. Postoperatively, some patients exhibit portal hypertension and progressive liver fibrosis. Splenomegaly is a symptom of portal hypertension. We aimed to investigate splenomegaly as a marker for complications of portal hypertension and the relationship between splenomegaly and liver fibrosis in the long-term native liver (NL). Methods Between 1977 and 2018, 71 patients underwent hepaticojejunostomy. We included 54 patients (34 NL group, 20 liver transplant (LT) group) who fulfilled the eligibility criteria. Spleen volume (SV), total bile acids, hyaluronic acid, type IV collagen, and aspartate aminotransferase-to-platelet ratio index (APRi) were measured. Data were analyzed using Student's t-test, regression analysis, and receiver operating characteristic (ROC) curve analysis (P Results Total bile acids, hyaluronic acid, type IV collagen, and APRi increased in NL patients with a large SV at >25 years. SV and type IV collagen were correlated with NL for >25 years (r = 0.79 [P = 0.006], y = 1.1 - [0.03 × type IV collagen] [P = 0.008]). In the ROC curve analysis, the cutoff value for type IV collagen was 165 ng/mL (P = 0.07). Conclusions We suggest that SV as a prognostic index for End-Stage Liver Disease may be useful in biliary atresia. Long-term follow-up is necessary because the clinical course may be favorable in childhood but worsen during adulthood.

The delineation and characterization of splenic lesions and other abnormalities can be challenging on computed tomography. Many splenic lesions are incidentally found, imaging features tend to overlap, and without the appropriate clinical context, differentials can range from benign to malignant. Radiologists should be familiar with the wide variety of pathologies seen on computed tomography as it is often the first imaging modality a splenic lesion is seen. The purpose of this MDCT-focused review is to understand normal splenic anatomy and its variants, to illustrate and describe typical and atypical imaging patters of inflammatory, infectious, vascular, traumatic, benign, and malignant tumors of the spleen and provide clues in reaching the appropriate differential diagnosis and management.

The major challenge in the treatment of autoimmune diseases is the restoration of the impaired peripheral immune tolerance that always accompanies the development of such diseases. Here, we show that small splenic peptides (SSPs) of whole spleen extract efficiently suppress the development of psoriatic arthritis in vivo, even in the presence of sustained levels of pro-inflammatory cytokines. SSPs target dendritic cells (DCs) and convert them into tolerogenic cells, which in turn differentiate naive CD4(+) cells into Foxp3-expressing T regulatory cells (Tregs). The latter requires direct contact between SSP-activated DCs and naive CD4(+) T cells via PD-1 and CTLA4 immune checkpoint receptors of T cells. Finally, depletion of Foxp3(+) Tregs in vivo abrogated the protective effect of SSPs on psoriatic arthritis development. We hypothesize that SSPs represent an intrinsic component of the adaptive immune system responsible for the physiological maintenance of peripheral tolerance and that therapeutically administered SSPs are able to restore imbalanced peripheral tolerance in autoimmune diseases.

Please see the Editorial Comment by Javier Villanueva-Meyer discussing this article. Background: Pegfilgrastim administration after chemotherapy increases bone marrow and spleen FDG uptake. Consens...

Brucella spp. are facultative intracellular pathogens that invade, survive and proliferate in numerous phagocytic and non-phagocytic cell types, thereby leading to human and animal brucellosis. Outer membrane proteins (Omps) are major immunogenic and protective antigens that are implicated in Brucella virulence. A strain deleted of the omp16 gene has not been obtained which suggests that the Omp16 protein is vital for Brucella survival. Nevertheless, we previously constructed an omp16 conditional deletion strain of Brucella, ΔOmp16. Here, the virulence and immune response elicted by this strain were assessed in a mouse model of infection. Splenomegaly was significantly reduced at two weeks post-infection in ΔOmp16-infected mice compared to infection with the parental strain. The bacterial load in the spleen also was significantly decreased at this post-infection time point in ΔOmp16-infected mice. Histopathological changes in the spleen were observed via hematoxylin-eosin staining and microscopic examination which showed that infection with the ΔOmp16 strain alleviated spleen histopathological alterations compared to mice infected with the parental strain. Moreover, the levels of humoral and cellular immunity were similar in both ΔOmp16-infected mice and parental strain-infected mice. The results overall show that the virulence of ΔOmp16 is attenuated markedly, but that the immune responses mediated by the deletion and parental strains in mice are indistinguishable. The data provide important insights that illuminate the pathogenic strategies adopted by Brucella.

Kurthia gibsonii (H. Kurth, 1883) was isolated on 10 unrelated laying hen farms over a period of 15 months. Farmers reported elevated morbidity and mortality rates, and suspected of colibacillosis based on the necropsy findings. The most frequently found lesions were perihepatitis, fibrinous peritonitis, salpingitis and oophoritis. Necropsy findings and bacteriological results allowed the diagnosis of colibacillosis. In addition, K. gibsonii was isolated from the ovarian follicles (44.44 %), liver (22.22%), peritoneum (16.67%), bone marrow (5.56%), spleen (5.56%), and duodenum (5.56%). On all farms, coinfection with E. coli was detected, while on some farms other common avian pathogens were found as well. In total, 18 K. gibsonii strains were identified and phylogenetically analysed based on the 16S rRNA gene sequences. The results showed some variability of the strains originating from the same farm, although the overall phylogenetic diversity was low, regardless of the geographical location of the farm, age of the flock or date of collection. Embryo lethality assay showed K. gibsonii is not able to cause a primary infection. We conclude that Kurthia gibsonii may play a role as an opportunistic pathogen for poultry. This is the first report of coinfection of Kurthia gibsonii and E. coli in laying hens.

Obesity impairs host defense against Klebsiella pneumoniae, but responsible mechanisms are incompletely understood. To determine the impact of diet-induced obesity on pulmonary host defense against K. pneumoniae, we fed 6-wk-old male C57BL/6j mice a normal diet (ND) or high-fat diet (HFD) (13% vs. 60% fat, respectively) for 16 wk. Mice were intratracheally infected with Klebsiella, assayed at 24 or 48 h for bacterial colony-forming units, lung cytokines, and leukocytes from alveolar spaces, lung parenchyma, and gonadal adipose tissue were assessed using flow cytometry. Neutrophils from uninfected mice were cultured with and without 2-deoxy-d-glucose (2-DG) and assessed for phagocytosis, killing, reactive oxygen intermediates (ROI), transport of 2-DG, and glucose transporter (GLUT1–4) transcripts, and protein expression of GLUT1 and GLUT3. HFD mice had higher lung and splenic bacterial burdens. In HFD mice, baseline lung homogenate concentrations of IL-1β, IL-6, IL-17, IFN-γ, CXCL2, and TNF-α were reduced relative to ND mice, but following infection were greater for IL-6, CCL2, CXCL2, and IL-1β (24 h only). Despite equivalent lung homogenate leukocytes, HFD mice had fewer intraalveolar neutrophils. HFD neutrophils exhibited decreased Klebsiella phagocytosis and killing and reduced ROI to heat-killed Klebsiella in vitro. 2-DG transport was lower in HFD neutrophils, with reduced GLUT1 and GLUT3 transcripts and protein (GLUT3 only). Blocking glycolysis with 2-DG impaired bacterial killing and ROI production in neutrophils from mice fed ND but not HFD. Diet-induced obesity impairs pulmonary Klebsiella clearance and augments blood dissemination by reducing neutrophil killing and ROI due to impaired glucose transport.

The spleen is the most commonly injured solid organ following blunt abdominal trauma. Over recent decades, splenic artery embolization (SAE) has become the mainstay treatment for haemodynamically stable patients with high-grade blunt splenic trauma, with splenectomy the mainstay of treatment for unstable patients. Splenic function is complex but the spleen has an important role in immune function, particularly in protection against encapsulated bacteria. Established evidence suggests that following splenectomy immune function is impaired resulting in increased susceptibility to overwhelming post-splenectomy infection, however, immune function may be preserved following SAE. This review will discuss the current state of the literature on immune function following different treatments of blunt splenic injury, and the controversies surrounding what constitutes a quantitative test of splenic immune function.

The study explored on the effects of dietary 0.4% dandelion extract on the growth performance, serum biochemical parameters, liver histology and the expression levels of immune and apoptosis-related genes in the head kidney and spleen of hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) at different feeding period. The results showed that the weight gain rate (WGR) of the hybrid grouper were significantly increased at the second and fourth weeks (P 0.05), but there was no significant difference in WGR at the eighth week (P 0.05). Compared with the control group, dietary dandelion extracts supplementation improve lipid metabolism, reduce lipid accumulation in liver and maintain normal liver histology at the second and fourth weeks. At the end of the second week, the relative expression levels of antioxidant related genes (MnSOD, GPX and GR) in the head kidney of hybrid grouper fed with dandelion extract increased significantly; at the end of week 4 and week 8, the relative expression levels of antioxidant related genes other than MnSOD did not change significantly. However, in the spleen of hybrid grouper, the expression of these antioxidant genes showed the opposite trend. At the end of the eighth week, dietary dandelion extract supplementation significantly increased the expression of inflammatory response related genes in head kidney of hybrid grouper, but showed the opposite trend in spleen. In conclusion, the short-term (2 or 4 weeks) application of 0.4% dandelion extract in feed had the effects of growth improvement, liver protection and immune stimulation on hybrid grouper due to its antioxidant and anti-inflammatory activities. The beneficial effect of dandelion extract on hybrid grouper was time-dependent, and its action time on different immune organs of hybrid grouper was not synchronous.

Objective To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

The SARS-CoV-2 pandemic spread worldwide unabated. However, achieving protection from the virus in the whole respiratory tract, avoiding blood dissemination, and calming the subsequent cytokine storm remains a major challenge. Here, we develop an inhaled microfluidic microsphere using dual camouflaged methacrylate hyaluronic acid hydrogel microspheres with a genetically engineered membrane from angiotensin-converting enzyme II (ACE2) receptor-overexpressing cells and macrophages. By timely competing with the virus for ACE2 binding, the inhaled microspheres significantly reduce SARS-CoV-2 infective effectiveness over the whole course of the respiratory system in vitro and in vivo. Moreover, the inhaled microspheres efficiently neutralize proinflammatory cytokines, cause an alternative landscape of lung-infiltrated immune cells, and alleviate hyperinflammation of lymph nodes and spleen. In an acute pneumonia model, the inhaled microspheres show significant therapeutic efficacy by regulation of the multisystem inflammatory syndrome and reduce acute mortality, suggesting a powerful synergic strategy for the treatment of patients with severe COVID-19 via non-invasive administration., Graphical abstract, Progress and potential The SARS-CoV-2 pandemic spread worldwide unabated. Protection of the whole course of the respiratory airway remains a major challenge. In this work, inhaled microfluidic methacrylate hyaluronic acid hydrogel microspheres (termed iAE-PMS) have been genetically engineered with ACE2 membranes and proinflammatory macrophages for competing viruses and cytokine binding. The iAE-PMS with wide distribution enables deposition throughout the respiratory system, providing protection for not only the lung but also the upper respiratory tract and nasopharynx. Furthermore, iAE-PMS presents clearance by the swinging of the cilia and enzymatic hydrolysis. The microspheres captured by cilia effectively reduce the virus output from the infected person to the environment. The respiratory-confined degradation significantly avoids systemic viral spreading. This inhaled microsphere is proposed as a powerful synergic strategy for the treatment of patients with severe COVID-19 via non-invasive administration., Inspired by SARS-CoV-2 infecting alveolar epithelial cells through ACE2 receptors, an inhaled modular microfluidic microsphere aerosol was developed using dual camouflaged methacrylate hyaluronic acid hydrogel microspheres with a genetically engineered membrane from ACE2 receptor-overexpressing cells and proinflammatory macrophages to capture the virus over the whole course of the respiratory tract before viremia occurs.

Background. Primary transitional cell carcinoma (TCC) of the ovary is characterized by the presence of papillary projections of malignant transitional epithelial cells or their aggregates in the fibrous stroma. This type of tumor represents nearly 1% of all ovarian surface epithelium carcinomas. We presented the first report of a solitary splenic metastasis of primary ovarian TCC. Case report. A 60-year-old female patient was admitted because of an asymptomatic splenic tumor in December 2018. Two years prior, she underwent a total abdominal hysterectomy, bilateral adnexectomy, and infracolic omentectomy for the primary TCC of the ovary. Control abdominal ultrasonography, computed tomography, and magnetic resonance imaging performed two years after primary surgery showed a splenic tumor. An open splenectomy was performed, with the intraoperative finding of a hilar splenic tumor and the absence of other pathological lesions in the abdomen. Frozen section analysis showed a TCC metastasis, which was subsequently confirmed by definitive histopathological examination. During the one-year follow-up, there was no relapse of the disease. Conclusion. This is the first report of a solitary splenic metastasis of primary ovarian TCC based on the literature review. This case may serve as an example of the diagnostic and therapeutical role of splenectomy in isolated splenic metastases of ovarian cancer.

The purpose of the current study was to explore the immunomodulatory effects of different adjuvants combined with inactivated vaccines under Aeromonas veronii TH0426 infection in crucian carp. This study explored the best conditions for A. veronii as an inactivated vaccine, and included an animal safety test. Furthermore, we expressed the flagellin FlaA of the A. veronii TH0426 strain for use as an adjuvant supplemented in the diet. Crucian carp were fed 12 different experimental diets for 35 days, including the administration of 10 different adjuvants and inactivated vaccine combinations (50% aluminum hydroxide gel and inactivated vaccine combination, and inactivated vaccine with 20%, 30%, or 50% glucan, astragalus polysaccharide or flagellin), inactivated vaccine alone, and PBS control without adjuvant and inactivated vaccine. After the 42 day feeding trials, the fish were challenged with A. veronii TH0426, and the survival rate over 14 days was recorded. In addition, flagellin FlaA can be expressed normally in large amounts. All experimental groups produced higher levels of IgM serum titres than the control group in the different feeding cycles. Moreover, the activity of serum ACP, AKP, SOD, and LZM, and the expression of inflammatory factors were significantly increased in the experimental groups compared with the control group. The results of qRT-PCR analysis showed that the transcription levels of the IL-10, IL-1β, IFN-γ and TNF-α genes in heart, liver, spleen and kidney tissues were significantly enhanced by adjuvant treatment, indicating that the addition of adjuvants can significantly promote the body's inflammatory response. In addition, the phagocytic activity of leukocytes in each adjuvant treated group was significantly enhanced compared to that in the groups without adjuvant. After the A. veronii challenge, the survival rate of all adjuvant-treated groups was significantly higher than that of the control group, and the 50% flagellin adjuvant group had the highest rate of 78.37%. Overall, our findings strongly indicate that adjuvants not only significantly improve the body's immunity, but also exhibit a strong anti-infection ability. Importantly, this work provides a new perspective for the prevention and control of aquaculture diseases.

Erythrocytes capture pathogens in circulation and present them to antigen-presenting cells (APCs) in the spleen. Senescent or apoptotic erythrocytes are physiologically eliminated by splenic APCs in a non-inflammatory manner as to not induce an immune reaction, while damaged erythrocytes tend to induce immune activation. The distinct characteristics of erythrocytes in their lifespan or different states inspire the design of targeting splenic APCs for vaccine delivery. Specifically, normal or damaged erythrocyte-driven immune targeting can induce antigen-specific immune activation, whereas senescent or apoptotic erythrocytes can be tailored to achieve antigen-specific immune tolerance. Recent studies have revealed the potential of erythrocyte-based vaccine delivery; however, there is still no in-depth review to describe the latest progress. This review summarizes the characteristics, different immune functions, and diverse vaccine delivery behaviors and biomedical applications of erythrocytes in different states. This review aims to contribute to the rational design and development of erythrocyte-based vaccine delivery systems for treating various infections, tumors, inflammatory diseases, and autoimmune diseases.

We sought to determine whether the amniotic cavity/fluid could be an attainable route of administration of therapeutic antibodies to the fetus/neonate.Time-dated pregnant dams (n = 9) received volume-matched intra-amniotic injections of either saline (n = 29), or different concentrations of a human IgG that lacked homology with rodents: 5 mg/mL (n = 28); 10 mg/mL (n = 28); or 15 mg/mL (n = 24). At term, the presence of the IgG was quantified by ELISA in the serum, bone marrow, spleen, thymus, and brain of all neonates, and in the maternal serum. Statistical analysis was by median regression with significance set at Bonferroni-adjusted p0.008.Overall fetal survival was 83% (90/109), with no difference between the groups. Human IgG was detected in the serum, bone marrow, spleen, thymus, and brain of all fetuses for all three injected concentrations, but not in the saline injected controls (p0.001). A dose dependent relationship between injection concentration and final IgG load was noted in the bone marrow, spleen, and thymus (p = 0.004 to0.001). Human IgG was also detected in maternal serum.IgG antibodies can reach high levels in the fetal/neonatal circulation after simple intra-amniotic administration in a healthy rodent model. Transamniotic fetal immunotherapy (TRAFIT) may become a practicable strategy for the perinatal management of select diseases.N/A (animal and laboratory study) TYPE OF STUDY: Animal and laboratory study.

Nlrp3 is a vital integration point of diverse extracellular stimuli and cellular stress. However, inappropriate activation of Nlrp3 results in progression of autoinflammatory and metabolic disorders. Atrazine, using widely in agricultural sector, is a toxic environmental factor for human. Here, this study found that atrazine could induce oxidative stress and the expression of Nfkb and IRF1 in spleen, promoting the ox-mtDNA formation. And production and release of ox-mtDNA stimulated the Nlrp3 inflammasome. Lastly, atrazine induced the pyroptosis in spleen mediating the activation of Nlrp3 inflammasome. Additionally, lycopene, a kind of carotenoid, is natural bioactive component in fruits and vegetables, which is applied towards reducing oxidative stress. It was found that lycopene could ameliorate the pyroptosis induced by atrazine via inhibition of the ox-mtDNA production. The results also provided evidence that lycopene had the potential role in prevention Nlrp3 inflammasome activation by depleting the ox-mtDNA.

Background Cytauxzoon felis is a life‐threatening protozoan disease of cats. Identification of schizont‐laden macrophages is a point‐of‐care diagnostic test for acute cytauxzoonosis. Hypothesis/Objectives The primary objective determined cytologic agreement between sample types to diagnose acute cytauxzoonosis. The secondary objective evaluated novices' ability to identify cytauxzoon organisms in blood films and tissue aspirates. Animals Thirty‐eight cats with suspected acute cytauxzoonosis and 5 controls examined postmortem. Methods Cases were prospectively submitted and collected. Blood film, lymph node, and splenic aspirates were blindly reviewed for sample quality, presence of schizont‐laden macrophages, and agreement between sample types. A subset of cases and controls were evaluated by 12 blinded novice observers to determine sensitivity and specificity for identifying organisms in various sample types. Results Acute cytauxzoonosis diagnosis was made on at least 1 sample type in 28/38 cats. Schizont‐laden macrophages were seen on 33% (10/30) of blood films, 56% (19/34) lymph node aspirates, 77% (26/34) splenic aspirates. Schizont‐laden macrophages were more likely seen on splenic than lymph node aspirates (McNemar's, P = .03) or blood film (McNemar's, P =

A 19-year-old female patient presented with Staphylococcus aureus infective endocarditis, with suspected subdural brain hemorrhage, disseminated intravascular coagulopathy, and septic renal as well as spleen infarcts. The patient had extensive vegetations on the mitral and tricuspid valves and underwent urgent mitral and tricuspid repair. This paper discusses the clinical case and current evidence regarding the management and treatment of Staphylococcus aureus endocarditis.

Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are common immunosuppressive cells in the tumor microenvironment. These cells, through various mechanisms, inhibit antitumor immune responses and impede effective therapies. Therefore, designing an efficient protocol for inducing immune surveillance in tumors is highly recommended. Recently, nanoliposomes have provided broad-spectrum and state-of-the-art vehicles to deliver antigens or immune system compartments in immunotherapies. It has been shown that different lipids in the structure of liposomes and various liposomal formulations can affect immune responses in the tumor microenvironment. This study was aimed to evaluate the effects of four different liposomal formulations on MDSCs and Tregs in C26 tumor-bearing mice. To this end, after preparing liposomes, they were injected into tumor-inoculated mice and analyzed MDSC and Treg population and functions in spleen and tumor tissues. Results showed that DOTAP-containing liposomes reduced MDSC population and activity in the spleen, but not tumor, compared with other groups significantly (P

Tumor antigens (Ags) are weakly immunogenic and elicit inadequate immune responses, thus induction of antigen-specific immune activation via the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy. In this study, we examined the effect of Rv3628 from Mycobacterium tuberculosis (Mtb) on activation of DCs and anti-tumor immunity in vivo. Intravenous injection of mice with Rv3628 promoted DC activation of spleen and lymph nodes. More importantly, Rv3628 also induced activation of DCs and enhanced Ag presentation in tumor-bearing mice. In mice bearing ovalbumin (OVA)-expressing tumors, combination treatment with Rv3628 and OVA peptide promoted OVA-specific T cell activation and accumulation of interferon (IFN)-γ and tumor necrosis factor (TNF)-α-producing OT-I and OT-II cells in tumor-draining lymph nodes. Moreover, three different tumor Ags in three different tumor models showed enhanced anti-tumor activity with Rv3628 as adjuvant, including inhibition of growth of OVA-expressing B16 melanoma, CT26 carcinoma, and B16 melanoma tumors, and a synergistic effect with anti-programmed cell death protein 1 (PD-1) antibody treatment. Additionally, potential application against human tumors was indicated by similar activation of human peripheral blood DCs by Rv3628. Taken together, these data demonstrate that Rv3628 could be an effective adjuvant in tumor immunotherapy via enhanced capacity of DC activation and Ag presentation., Graphical abstract, This study investigated the effect of Rv3628 from Mycobacterium tuberculosis (Mtb) on activation of dendritic cells (DCs) and anti-tumor immunity in vivo. The results demonstrate that Rv3628 activates DCs in TLR2-dependent manner, and could be an effective adjuvant in tumor immunotherapy via enhanced capacity of DC activation and antigen presentation.

The present study investigated the virulence and expression of innate immunity genes in isolates of infectious hematopoietic necrosis virus (IHNV) in Gangwon province, South Korea, by challenging rainbow trout, Atlantic salmon, and coho salmon. Eight IHNV isolates were used to infect RTG-2 cells for viral replication using plaque assays. Three isolates with the highest replication rates, the RtPc0314g and RtPc0314c isolates of the JRt-Shizuoka type and the RtPc0816g isolate of the JRt-Nagano type, were experimentally infected into the fish. In rainbow trout, both RtPc0314c and RtPc0314g isolates showed 100% cumulative mortality while the RtPc0816g isolate showed 60% cumulative mortality for 14 days. In contrast, all three isolates showed

Introduction Soluble forms of cytokine receptors can be involved in the endogenous regulation of cytokine activity. Soluble interleukin 7 receptor α (sCD127) naturally binds IL‐7, therefore there is interest in its potential application as an immunotherapeutic agent to regulate IL‐7. With the hypothesis that sCD127 enhances IL‐7 activity, thus promoting T‐cell proliferation in vivo, we sought to assess the effect of sCD127, IL‐7 or IL‐7 + sCD127 treatment on CD4+ and CD8+ T‐cells in the blood and spleen of mice. Methods Peripheral blood mononuclear cells and splenocytes were prepared, and analyzed for T‐cell number, phenotype and proliferation (Ki67+) by flow cytometry. Results IL‐7 treatment induced T‐cell proliferation, increased T‐cell number, and triggered T‐cell differentiation each of which was enhanced with the addition of sCD127. IL‐7 + sCD127 treatment significantly increased spleen weight over that seen with IL‐7 treatment alone. More pronounced proliferation and a greater increase in cell number was observed in CD8+ T‐cells relative to the effect on CD4+ T‐cells. Conclusions These findings suggest that the addition of sCD127 enhances IL‐7‐mediated T‐cell proliferation and suggests a potential therapeutic use for sCD127., IL‐7 alone can have a positive effect on T‐cell proliferation and T‐cell differentiation from a naive T‐cell. In this mouse study, we found that complexing IL‐7 with soluble CD127 could enhance these positive effects, suggesting a therapeutic use in vivo.

Hematopoietic stem cells (HSCs) have been studied extensively since their initial functional description in 1961 when Dr. James Till and Dr. Ernest McCulloch developed the first in vivo clonal strategy, termed the "spleen colony-forming unit" (CFU-S) assay, to assess the functional capacity of bone marrow–derived hematopoietic progenitors at the single-cell level. Through transplantation of bone marrow cells and analysis of the resulting cellular nodules in the spleen, the CFU-S assay revealed both the self-renewal and clonal differentiation capacity of hematopoietic progenitors. Further development and use of this assay have identified highly proliferative, self-renewing, and differentiating HSCs that possess clonal, multilineage differentiation. The CFU-S strategy has also been adapted to interrogating single purified hematopoietic stem and progenitor cell populations, advancing our knowledge of the hematopoietic hierarchy. In this review, we explore the major discoveries made with the CFU-S assay, consider its modern use and recent improvements, and compare it with commonly used long-term transplantation assays to determine the continued value of the CFU-S assay for understanding HSC biology and hematopoiesis.

Inflammatory pseudotumor (IPT)-like follicular dendritic cell sarcoma (FDCS) is an extremely rare malignant neoplasm.Retrospective analysis of imaging features of splenic IPT-like FDCS, including ultrasonography, computed tomography (CT), and magnetic resonance (MR) and contrast-enhanced imaging were performed.When the masses were small, the ultrasound images showed homogeneous hypoechoic signals, clear boundaries, and complete capsules. Abdominal plain CT scans showed equal density (easy to miss diagnosis), unclear boundaries, and no capsules. Magnetic resonance images (MRI) showed slightly shorter T1, slightly shorter T2, and clear boundaries. When the masses were large, the ultrasound images still showed clear boundaries and complete capsules, but the echoes of the masses were not uniform, and some of the masses showed dendritic hyperechoic centers. Abdominal plain CT scans showed irregular low densities in the center (unclear boundaries) and equal densities in the periphery. MRI showed short T1 and T2, but the central signals were mixed. When the mass was accompanied by extensive necrosis, abdominal plain CT scan showed mostly cystic lesions and slight calcifications in low density lesions. Contrast-enhanced CT showed only moderate enhancement in peripheral and septal areas. MRI showed that T1 and T2 were mainly mixed signals. Contrast-enhanced MR showed moderate enhancement of peripheral areas and septum.This is the first report to describe the IPT manifestations of the spleen (ultrasonography, CT, and MR). The diagnosis of IPT can be made by combining three imaging features.

Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important pathogen of hospital-acquired (HA) or community-acquired (CA) infections. However, it is unclear of the cytokines responsible for pathological hyper-inflammation in sepsis related cytokine storm for MRSA infection. In this study, we selected typical HA-MRSA strain (YNSA163: ST239-t030-SCCmecⅢ) and two CA-MRSA isolates (YNSA7: ST59-t439-SCCmecⅣa and YNSA53: ST59-t437-SCCmecⅤb) from our previous research, infected on BALB/c mice, and analyzed the cytokine storm patterns during infection process. The animal experiments revealed the most serious lethal effect on BALB/c mice caused by YNSA7 strain infection, followed by YNSA53, and no BALB/c mice died for YNSA163 infection. Histopathological analyses revealed that lung was the most seriously damaged organs, followed by spleen and kidney, especially for CA-MRSA infection. The severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in CA-MRSA strains infected mice. Interleukin-6 (IL-6) and IL-10 were both highly expressed in spleen and lung of YNSA7 and YNSA53 dead cases compared with YNSA53 survived and YNSA163 cases, which demonstrated cytokine storm pattern for CA-MRSA strains infection. The results of IL-6 intervention experiment verified that the enhanced IL-6 secretion was responsible for the host lethality of YNSA7 infection. RNA-sequencing results among three MRSA isolates indicated most of the differentially expressed genes referred to cellular process, metabolism and genetic information processing of bacteria. Specifically, clpP, chp chemotaxis inhibit, fnbB, pathogencity island protein and virulence associated protein E were highly expressed in YNSA7 strain. In general, CA-MRSA strains provoked cytokine storm on BALB/c mice led to severe infection and lethality, the up-regulated of some virulence genes might play important role in pathogenesis.

In spring 2020, a severe disease outbreak with high morbidity and mortality was observed in a collection of 15 Horsfield’s tortoises (Testudo horsfieldii). Affected tortoises showed upper respiratory- and gastrointestinal tract signs, including rhinitis and stomatitis. Testudinid herpesvirus 1 (TeHV1) and Mycoplasma spp. were detected by PCR in oral swabs of affected animals. Histological examination of one deceased animal showed intranuclear inclusion bodies typical for herpesvirus infections in liver, spleen and oesophagus. The virus was likely introduced into the collection 2 years earlier by a clinically healthy Horsfield’s tortoise that was tested positive for TeHV1 by PCR.

Splenic rupture and/or splenectomy is/are not uncommon in clinical arena. Here we present this case of extensive haemorrhage-induced splenic rupture which resulted in splenectomy in a young healthy male (who did not have any previous medical conditions) following a Russell's viper bite. He developed upper abdominal and shoulder pain on his left side along with hypotension and reduced level of haemoglobin on the third day following bite despite antivenom treatment. Following confirmation of splenic rupture and haemoperitoneum by ultrasound and computed tomography scans, an emergency splenectomy was performed using laparotomy. Although Russell's viper bites are known to induce bleeding complications, splenic rupture due to haemorrhage in spleen has not been previously reported. Russell's viper venom toxins such as metalloproteases, serine proteases and phospholipase A2 might have affected the vascular permeability resulting in excessive bleeding and increased pressure in the spleen leading to rupture. Further investigations are required to underpin the impact of snake venom toxins on the architecture and functions of spleen. However, the clinicians who treat snakebites should be aware of this type of rare complications so as to provide appropriate management for such victims.

Fatal infections with Cytauxzoon felis are common in domestic cats, and jaguars (Panthera onca) are believed carriers of this protozoan. Fatal C. felis infections have never been described in jaguars before. Thus, this study describes such an infection in a 5-month-old captive-reared jaguar that presented hyporexia and died at 26 days after the first clinical signs. During necropsy, samples were taken from several tissues, some were fixed in 10% formalin and process for histopathological diagnosis, and some samples were used for DNA extraction, amplification via PCR and sequencing of the potential pathogens. Grossly, marked splenomegaly and icterus were observed. Histologically, numerous structures that are morphologically compatible with Cytauxzoon spp. schizonts obliterated multiple blood vessels in the brain, leptomeninges, spinal cord, lungs, heart, skeletal muscle, adrenal gland, kidneys, spleen, small intestine and pancreas. C. felis was identified by PCR in many organs. Thus, C. felis infection in jaguars can be fatal, and the clinicopathological findings are similar to those of cytauxzoonosis in other wild and domestic felid species., Graphical abstract Image 1, Highlights • Cytauxzoon felis causes fatal infection in jaguar (Panthera onca). • Clinicopathological findings are similar to the infection in other felids. • Cytauxzoonosis should be investigated in young jaguars with jaundice.

Peste des petits ruminants (PPR) is an intense and extremely contagious disease with high mortality in small ruminants resulting inconsiderable socio-economic impact in developing countries. Our study was established during the routine follow up in El-Giza governorate during 2019. A total number of 45 swabs, 40 sera samples and 15 post-mortem epithelial tissues were collected from sheep showing clinical signs suggestive for PPR.PPRVdetection was investigated using serological, pathological and RT-PCRdiagnosis tests.Serologically, PPRV antigens detection were 86%, 93.3%, 66.63% and 73.3% in the nasal, ocular, faecal swabs and different tissues samples, respectively. While, PPRV antibodies detection were 95% in the collected sera samples.Histopathologically, the lung showed severe bronchiectasis and syncytium formation with high accumulation of inflammatory cells. The liver exhibited necrosis with severe portal and central hypertension filled with inflammatory cells.The kidneys revealed severe atrophied glomeruli with destructed renal glomerular capillaries, hemorrhage in the glomeruli and renal tubules with thrombosis of blood vessels. Spleen revealed proliferation of central arterioles with periarteriolar proliferation of connective tissues and hypercellular red pulp with hemorrhage. The mouth commissures suffering from nodules and ulceration which exhibited microscopically multiple vesicles in the epidermis and dissociation of the epidermal and dermal layers filled with inflammatory cells and eosinophils with syncytium formation. A 448 bp band by RT-PCRwas obtained from all nasal and ocular samples, while 2 lung samples were negative for this test.Therefore, the results proved the presence of the disease in El-Giza governorate.

Particularity of ocular immunity is manifested by "Immune privilege". For example, it has been generally known that corneal transplantation is a typically successful organ transplantation compared with other organs. This immune privilege can be explained by "immune-suppressive ocular microenvironment" and "anterior chamber-associated immune deviation, ACAID". This review focused on molecular mechanisms of the "immune-suppressive ocular microenvironment" and "ACAID", so that possible anti-inflammatory strategies could be raised. Especially, in murine ACAID model, anti-inflammatory actions were induced probably through induction of Treg cells. As an anti-inflammatory strategy, anti-inflammatory Treg cells could be induced in vitro. Treg cells that are specifically responsive for a specific antigen can be induced by culturing spleen cells with the antigen and transforming growth factor-β (TGF-β). The induced Treg cells were activated by stimulation with the specific antigen. When the induced Treg cells were adoptively transferred to recipient mice, antigen-induced inflammation was effectively suppressed. The Treg cells may be able to be efficiently induced by eye-based mechanisms. Further analyses of mechanisms underlying the ocular immune privilege can be useful for development of new anti-inflammatory strategies on the eye basis.

Memory T (TM) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how TM cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, TM cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin+ cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of TM cells. The numbers of CD127hiCD62Lhi TM cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127loKLRG1hi TM cells were adoptively transferred into anti–N-cadherin–treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, without functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127hiCD62Lhi TM cells and homing of CD127loKLRG1hi TM cells to lymphoid organs.

This article presents a review of the methods of determining spleen size in sonography, computed tomography, and magnetic resonance imaging. The review aims to summarize the data on the methods of estimating the linear dimensions of the spleen and splenic volume and describe the physiological variability of spleen size depending on sex, age, and different physiological conditions. We systematized the methods used for measuring the spleen and presented them in the form of a table, analyzed the results of previous studies, and compared the accuracy of different methods of calculating the splenic volume using a variety of diagnostic methods.

BACKGROUND: Recently, the problem of changes in immunological reactivity has become important with the growth of immunodeficiency states of a different nature. [4]. High radiosensitivity of the immune system, its stability in time and the irreversibility of some post-radiation changes can contribute to the development of long-term effects of radiation [2,3,6]. One of the tasks of modern medicine and biology is to study the effect of chronic or fractionated ionizing effects on the body's immune system both in the early and late periods of irradiation and their 1st generation descendants [1,2,3,11,12]. Therefore, it is necessary to study the long-term effects of sublethal and fractionated effects of g-radiation on the immunological reactivity of the organism, nonspecific phagocytic resistance and their 1st generation descendants. AIM: The aim of this study was to study the long-term effects of sublethal and fractionated effects of g-radiation on the immunological reactivity of the organism, nonspecific phagocytic resistance and their 1st generation descendants.. METHODS: 7 series of experiments were performed on 105 white outbred sexually mature rats. 1-series intact (n=15), 2nd series - (n = 15) irradiated with a sublethal dose of 6 Gr. (1 month), 3rd series - irradiated with a sublethal dose (3 months, n = 20), 4 - descendants 1 - generations after sublethal dose, 5 series - irradiated with a fractionated dose (1 month), 6 series - irradiated with a fractionated dose (3 months), 7 - descendants of the 1st generation after fractionated -irradiation. Each series used 15 animals. Irradiation of animals 2 - 3 - 4 series was carried out on the Russian radiotherapy device "Agat-RM" -rays 60Co, the dose of sublethal irradiation is 6 Gr. Irradiation of animals of 5-6-7 series was carried out on the Russian radiotherapy device "Agat-RM" with 60Co-rays with topometric and dosimetric preparation of experimental animals, which facilitates the administration of a fractionated dose of 2 Gr. to animals three times within 3 weeks. RESULTS: In the long-term period after fractionated g-irradiation in the T-system of immunity, the following changes occur: against the background of an increase in the total number of lymphocytes, there is a decrease in the pool of CD3 +, CD4 + lymphocytes, immunoregulatory index, normalization of the lymphokine-producing ability of lymphocytes and a decrease in the pool of CD8 + lymphocytes. In the long-term period after fractionated g-irradiation in the humoral link of immunity, an increase in the absolute amount of CD19 + by 3.5 times was noted, which significantly exceeded the indicators of both control and intact animals. The percentage of this pool of cells exceeded the data of intact ones by 1.7 times. In the studied time period, the antibody-producing ability in the spleen increased from 22 ± 1.3 to 45 ± 2.6, without reaching, however, the level of intact animals. At the same time, there was a significant decrease in the suppression index to 13% (P

Background Splenic autotransplantation is a promising method to recover splenic functions after traumatic splenectomy. However, it is associated with several postoperative complications, such as subphrenic abscess, intestinal obstruction and torsion of the omentum with necrosis of the implanted splenic tissues. Therefore, the aim of this study is to evaluate a new splenic autotransplantation technique that could overcome those complications. Materials and methods A single segment of the spleen was implanted inside a pedunculated omental pouch and fixed in the native site of the spleen in 15 patients who underwent splenectomy for abdominal trauma. This group of patients was compared with the next 17 patients who underwent splenectomy alone. Additionally, splenic functions of the patient and control groups were evaluated 3 months using peripheral blood smear [the presence of Howell-Jolly (HJ) bodies] and abdominal contrast-enhanced computed tomography (CECT). Results All patients who underwent splenic autotransplantation showed evidence of a well-vascularised splenic tissue on CECT and normal peripheral blood smear without HJ bodies 3 months postoperatively. No postoperative complications related to splenic autotransplantation were observed, and platelet count after 3 months was significantly higher in patients who underwent splenectomy only (p = 0.04). Conclusions Splenic autotransplantation using the aforementioned technique could restore splenic functions with minimum postoperative complications related to the procedure.

Luteinizing hormone receptor (LHR), prolactin receptor (PRLR), growth hormone (GH) and insulin-like growth factor 1 (IGF1) have been shown to be key regulators of germ cell development. However, the role of LHR, PRLR, GH and IGF1 in the development of yak testis remains unclear. In this study, we aimed to describe and compare gene expression and protein localization of LHR, PRLR, GH and IGF1 in the development of yak testes. Testes were collected from 6, 24, 36 and 72 months yak, and the kidney, liver, testicular, lung, skeletal muscle, heart and spleen tissues were collected from 36 months yak. The quantitative real-time PCR (qRT-PCR) results showed that the expression of these four genes was widely expressed in kidney, liver, testicular, lung, skeletal muscle, heart and spleen, while the LHR and PRLR were highly expressed in the kidney, skeletal muscle and testis, and higher levels of GH and IGF were expressed in spleen and testis. Moreover, the mRNA expression of these genes in adults was higher than in pre-pubertal yak. In the testis, the LHR-, PRLR-, GH- and IGF1-positive signals were detected in the Leydig cells of the 6 months, while the intense positive signals were discovered in Leydig cells, spermatogonia and spermatocytes of the 36 and 72 months. Thus, LHR, PRLR, GH and IGF1 may be involved in the development of spermatids and spermatocytes, and in the regulation of spermatogonia proliferation and Leydig cell function.

Cytokines play critical roles in regulating iNKT cell development, activation, and maturation. TNF-α co-occurs with iNKT cells in steady-state and many disease conditions. How TNF-α affects iNKT cell function has not been thoroughly investigated. It was found that chronic alcohol consumption enhanced iNKT cell activation and maturation. The underlying mechanism is not known. Herein, a TNF-α KO mouse model was used to address these issues. It was found that the depletion of TNF-α mitigated alcohol consumption-enhanced iNKT cell activation and maturation. In steady-state, depletion of TNF-α did not affect the frequency of iNKT cells in the thymus and spleen but decreased iNKT cells in the liver and increased liver iNKT cell apoptosis. The portion of stage-2 immature iNKT cells increased, stage-3 mature iNKT cells decreased in the thymus of TNF-α KO mice, suggesting that depletion of TNF-α impairs iNKT cell development and maturation. The percentage of CD69+ iNKT cells was significantly lower in the thymus, spleen, and liver of TNF-α KO mice compared to their wild-type littermates, suggesting that depletion of TNF-α inhibits iNKT cell activation. Moreover, the percentage of splenic IL-4- and IFN-γ-producing iNKT cells was significantly lower in TNF-α KO mice than in their wild-type littermates. The depletion of TNF-α increased PLZF+ iNKT cells in the thymus and down-regulated the expression of CD122 on iNKT cells. Collectively, these results support that TNF-α plays a vital role in the regulation of iNKT cell development, activation, and maturation, and alcohol consumption enhances iNKT cell activation and maturation through TNF-α.

OBJECTIVES This study aimed to clarify the regulatory role of Th17-Treg balance in periodontitis and further reveal Treg plasticity. MATERIALS AND METHODS An experimental periodontitis model was established by ligation and injection of Pg-LPS. Inflammatory factors were measured by ELISA and RT-PCR. Alveolar bone absorption was evaluated by micro-CT and histomorphology. Quantities of Treg and Th17 cell and their related gene expression were examined. Furthermore, after magnetic bead-sorting spleen Treg cells, Treg/Th17 characteristic genes were explored. Immunofluorescence double staining of Foxp3 and IL-17 was conducted to further reveal Treg plasticity. RESULTS Inflammatory cytokines in serum and gingival tissue increased significantly in periodontitis, which revealed obvious crestal bone loss. Further analysis showed that the number of Th17 cells and expression of related genes increased more significantly than Treg cells, demonstrating Treg-Th17 imbalance. Flow cytometry showed that the proportions of Treg cells in the blood and spleen were lower in periodontitis group. Furthermore, Foxp3 was downregulated, and Rorc/ IL-17A were increased in Treg cells of periodontitis group. Immunofluorescence double staining showed significantly increased number of IL-17+Foxp3+ cells in periodontitis. CONCLUSIONS These results provided evidence that Treg cells showed characteristics of Th17 cells in mice with periodontitis, although its mechanisms require further study.

Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide 2m, a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render 2m bioavailable and effective after its oral administration. The loading of 2m in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC50). In L. infantum-infected BALB/c mice, 2m-NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound 2m and its formulation merit further investigation as an oral treatment for visceral leishmaniasis.

To be investigated whether Th17/Treg cells regulated by Interleukin-6 in the pathogenesis of chronic rhinosinusitis with nasal polyps. The distributions of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) and tissues got from 46 CRSwNP patients and 14 controls were evaluated. Th17 and Treg cells and cells-related cytokines in serum were assessed in means of cytometric bead array (CBA) multiplex assays and enzyme-linked immunosorbent assays (ELISAs). Spleen cells were isolated from spleen of 20 normal BALB/c mice (male), isolated and purified with CD4 antibody immunomagnetic bead kit. CD4+ cells were divided into three groups, including TGF-β1, TGF-β1+ IL-6 and control (PBS). Treg and Th17 cells and cells related cytokines were detected by flow cytometry (FCM) after collecting spleen cells. The level of IL‐10 and IL‐17 in supernatant was measured by ELISA. Th17/Treg ratio and the level of IL-6 in both ECRSwNP (P

Background. Natural products have been said to show immunomodulatory and antioxidant activities. The research study was aimed to assess the immunomodulatory and free radical scavenging activities of crude polysaccharide from dry mushroom fruiting bodies of Termitomyces le-testui. Materials and Methods. Hot water extract of polysaccharide extract of T. le-testui was prepared and tested in white albino Wister rats for its immunomodulatory activities effect on methylprednisolone-immunosuppressed animals. In addition, the radical scavenging activity of the polysaccharide was evaluated using nitrite and hydrogen peroxide. Results. The result of the study showed that the polysaccharide T. le-testui increases the phagocytic index, energy metabolism of macrophages, spleen index, and nitric oxide in a concentration-dependent manner in immunosuppressed animals. Also, it was observed that the extract increased dose-dependent total oxidative stress and thymus index. Finally, the crude polysaccharide-rich extract showed nitrite and hydrogen peroxide scavenging activity in a concentration-dependent manner. Conclusion. Polysaccharide-rich extract possesses immunomodulatory and antioxidant properties.