[Treatment and prognosis of primary ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma: a report from a single center].

Objective: This study aimed to see how different initial treatment regimens affected the long-term prognosis of patients with extranodal marginal zone mucosa-associated lymphoid tissue lymphoma confining to the ocular adnexal (OAML) . Methods: Between April 2008 and April 2019, 109 patients with initial mucosa-associated lymphoid tissue confining to ocular adnexal were evaluated and followed-up, and the prognosis of various initial treatment regimens were examined. Results: A total of 36 patients underwent complete surgical resection of the lesions, and 73 patients had residual lesions after surgery, of which 37 patients chose watchful waiting, and 36 patients chose treatment. The treatment regimen included local radiotherapy and systemic treatment (chemotherapy, immunochemotherapy, the combination of radiotherapy and chemotherapy, etc.) , and no serious toxic and side effects were observed in patients receiving systemic treatment. The median follow-up time was 61 (10-142) months. The 5-year and 10-year progression-free survival (PFS) of monocular involvement patients were 78.2% and 76.0% . The 5-year and 10-year PFS rates of patients with binocular involvement were 64.4% and 23.5%. There was significant diference in PFS between patients with monocular and binocular involvement (P=0.010) . Patients who received additional treatment had higher PFS than those patients in the watchful waiting group (P=0.046) . The 5-year PFS was 71.4% and 90.1% among patients in the watchful waiting group and those who received additional treatment, whereas the 10-year PFS was 63.5% and 75.1% , respectively. Patients with OAML were still a risk of disease progression after 5 years. Conclusions: Patients with binocular involvement OAML at the start of the disease had a poor prognosis, but treatment could reduce the risk of recurrence/progression. Systemic therapy is one of the first-line treatment options for patients with OAML, who require long-term monitoring.

Artemisia argyi extract alleviates inflammation in a DSS-induced colitis mouse model and enhances immunomodulatory effects in lymphoid tissues.

BACKGROUND: The incidence of inflammatory bowel disease (IBD), an inflammatory disorder of the gastrointestinal system has increased. IBD, characterized by aberrant immune responses against antigens, is thought to be caused by the invasion of enterobacteria. The pathogenesis of IBD is complicated, hence novel effective therapeutic agents are warranted. Therefore, this study evaluates the potential of Artemisia argyi, a medicinal herb, in alleviating IBD. METHODS: The effectiveness of the A. argyi ethanol extract was verified both in vitro and in vivo. Inflammation was induced in RAW 264.7 cells by 1 µg/mL of lipopolysaccharide (LPS) and by 3% dextran sodium sulfate (DSS) in a DSS-induced colitis mouse model. During the ten-day colitis induction, 200 mg/kg of A. argyi ethanol extract was orally administered to the treatment group. Levels of inflammation-related proteins and genes were analyzed in the colon, serum, and lymphoid tissues, i.e., Peyer's patches (PPs) and spleen. The chemical constituent of the A. argyi ethanol extract was identified using an ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS) analysis. RESULTS: A. argyi ethanol extract treatment ameliorated IBD symptoms and reduced the expression of inflammation-related proteins and genes in the colon and serum samples. Furthermore, A. argyi treatment induced the activation of anti-oxidative associated proteins, such as nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1); and the treatment have also inhibited nuclear factor-κB (NF-κB), a central mediator of inflammatory responses. A. argyi enhanced the immunomodulatory effects in the PPs and spleen, which may stem from interleukin-10 (IL-10) upregulation. Chemical analysis identified a total of 28 chemical compounds, several of which have been reported to exert anti-inflammatory effects. CONCLUSIONS: The effectiveness of the A. argyi ethanol extract in alleviating IBD was demonstrated; application of the extract successfully mitigated IBD symptoms, and enhanced immunomodulatory responses in lymphoid tissues. These findings suggest A. argyi as a promising herbal medicine for IBD treatment.

Treatment and prognosis of primary ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma: a report from a single center / 中华血液学杂志

Objective: This study aimed to see how different initial treatment regimens affected the long-term prognosis of patients with extranodal marginal zone mucosa-associated lymphoid tissue lymphoma confining to the ocular adnexal (OAML) . Methods: Between April 2008 and April 2019, 109 patients with initial mucosa-associated lymphoid tissue confining to ocular adnexal were evaluated and followed-up, and the prognosis of various initial treatment regimens were examined. Results: A total of 36 patients underwent complete surgical resection of the lesions, and 73 patients had residual lesions after surgery, of which 37 patients chose watchful waiting, and 36 patients chose treatment. The treatment regimen included local radiotherapy and systemic treatment (chemotherapy, immunochemotherapy, the combination of radiotherapy and chemotherapy, etc.) , and no serious toxic and side effects were observed in patients receiving systemic treatment. The median follow-up time was 61 (10-142) months. The 5-year and 10-year progression-free survival (PFS) of monocular involvement patients were 78.2% and 76.0% . The 5-year and 10-year PFS rates of patients with binocular involvement were 64.4% and 23.5%. There was significant diference in PFS between patients with monocular and binocular involvement (P=0.010) . Patients who received additional treatment had higher PFS than those patients in the watchful waiting group (P=0.046) . The 5-year PFS was 71.4% and 90.1% among patients in the watchful waiting group and those who received additional treatment, whereas the 10-year PFS was 63.5% and 75.1% , respectively. Patients with OAML were still a risk of disease progression after 5 years. Conclusions: Patients with binocular involvement OAML at the start of the disease had a poor prognosis, but treatment could reduce the risk of recurrence/progression. Systemic therapy is one of the first-line treatment options for patients with OAML, who require long-term monitoring.

Effects of Hericium erinaceus polysaccharide on immunity and apoptosis of the main immune organs in Muscovy duck reovirus-infected ducklings.

To investigate the effects of Hericium erinaceus polysaccharide (HEP) on immunity in Muscovy duck reovirus (MDRV)-infected ducklings and explore its mechanism of action, an MDRV contact-infection model was established. Then, we investigated the influence of HEP on morphology of main immune organs in MDRV-infected ducklings by HE staining, while antioxidant capacity (T-AOC, MDA), serum protein levels (TP, ALB, GLO), complement levels (C3, C4) and antibody levels (IgA, IgM, IgG) were detected. Apoptotic indexes (apoptosisi rate and FAS-L) were also quantified by TUNEL method and immunohistochemical staining. Meanwhile, FADD and CytC (apoptosis-related genes), were tested by quantitative RT-PCR. Results showed that HEP could reduce the injuries of immune organs caused by MDRV. Additionally, HEP markedly diminished MDA (p < 0.01), while significantly increased T-AOC, TP, ALB, GLO, C3, C4, IgA, IgM and IgG (p < 0.01 or p < 0.05). Then, HEP shifted apoptosis time to an early MDRV-infected stage and reduced apoptosis at later MDRV-infected stage. This was associated with changes of FADD and CytC. Collectively, our data suggested that HEP could reduce the immunesuppression by many ways, such as decreasing organs' injuries, improving antioxidant capacity, serum proteins levels, antibody levels and complement levels, while diminish the apoptosis by lowering the FADD and CytC.

Berberine augments hypertrophy of colonic patches in mice with intraperitoneal bacterial infection.

Colonic patches, the counterparts of Peyer's patches in the small intestine, are dynamically regulated lymphoid tissues in the colon that have an important role in defensing against microbial infections. Berberine is an isoquinoline alkaloid extracted from medicinal herbs including Rhizoma coptidis and has long been used for the treatment of infectious gastroenteritis, but its impact on the colonic lymphoid tissues (such as colonic patches) is unknown. In this study, we aimed to investigate whether berberine had any influences on the colonic patches in mice with bacterial infection. The results showed that oral berberine administration in bacterial infected mice substantially enhanced the hypertrophy of colonic patches, which usually possessed the features of two large B-cell follicles with a separate T-cell area. Moreover, the colonic patches displayed follicular dendritic cell networks within the B-cell follicles, indicative of mature colonic patches containing germinal centers. Concomitant with enlarged colonic patches, the cultured colon of infected mice treated with berberine secreted significantly higher levels of interleukin-1ß (IL-1ß), IL-6, TNF-α, and CCL-2, while NLRP3 inhibitor MMC950 or knockout of NLRP3 gene abrogated berberine-induced hypertrophy of colonic patches, suggesting the involvement of the NLRP3 signaling pathway in this process. Functionally, oral administration of berberine ameliorated liver inflammation and improved formed feces in the colon. Altogether, these results indicated that berberine was able to augment the hypertrophy of colonic patches in mice with bacterial infection probably through enhancing local inflammatory responses in the colon.

Effects of mesalazine enemas on lymphoid follicular proctitis.

Lymphoid follicular proctitis (LFP) is an uncommon inflammatory disease that is characterized by rectal bleeding, congested and granular mucosa without ulceration and abnormal and coalescing hyperplastic lymphoid follicles without acute inflammatory changes. The lesions are usually confined to the rectal mucosa. LFP therapy is not well defined. Herein, we present a case of LFP that was resolved with a rapid administration of mesalazine enemas. A 35-year-old male was admitted to our hospital due to intermittent rectal bleeding associated with stools. Total colonoscopy revealed nodular mucosa with top pinpoint-like ulcers from the rectum to the border between the sigmoid flexure and the rectum. The nodules congested together on the lower rectal segment and occupied 2/3 of the rectal lumina. Endoscopic submucosal dissection was performed in order to obtain more specimens for histologic examination, which revealed marked lymphoid follicular hyperplasia with prominent germinal centers and a conserved mantle zone. Treatment was started with mesalazine enemas of 4 g q.d. and the patient was asymptomatic after three days. All the lesions disappeared two months later. Mesalazine enemas could be a promising and effective therapeutic option for LFP therapy.

Camel whey protein improves oxidative stress and histopathological alterations in lymphoid organs through Bcl-XL/Bax expression in a streptozotocin-induced type 1 diabetic mouse model.

Type I diabetes (T1D) is a characterized by the inflammation of pancreatic islets and destruction of ß cells. Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic individuals. Most serious diabetic complications are mediated by the free radicals, which damage multiple cellular components through direct effects of the cell cycle regulatory proteins. Camel whey protein (CWP) has antioxidant activity and decreases the effects of free radicals. However, the effects of CWP on lymphoid organs have not been studied in the context of diabetes. Therefore, the present study was designed to investigate the dietary influence of CWP supplementation on the lymphoid organs in streptozotocin (STZ)-induced type 1 diabetic mouse model. Three experimental groups were used: non diabetic control mice, diabetic mice, and diabetic mice treated with CWP. Induction of diabetes was associated with a marked reduction in glutathione (GSH) levels; decreased activities of GSH peroxidase (GSH Px), manganese superoxide dismutase (MnSOD) and catalase; increased reactive oxygen species (ROS) levels and iNOS activity in plasma and lymphoid organs. Furthermore, diabetic mice exhibited alterations in the expression of Bax and Bcl-XL, and subsequently pathological alterations in the architecture of the bone marrow, pancreas, thymus, and spleen. Interestingly, treatment of diabetic mice with CWP robustly restored glucose, insulin, GSH, and ROS levels and the activities of GSH Px, MnSOD, catalase and iNOS. Additionally, supplementation of diabetic mice with CWP improvement in the architecture of lymphoid tissues and rescued from apoptosis through direct effects on the Bax and Bcl-XL proteins. These data revealed the therapeutic potential of CWP against diabetic complications mediated damages of lymphoid organs.

Effect of Manual Lymphatic Drainage After Total Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of manual lymphatic drainage (MLD) on knee swelling and the assumed consequences of swelling after total knee arthroplasty (TKA). DESIGN: Randomized controlled trial. SETTING: Primary care hospital. PARTICIPANTS: Two groups of 30 patients were randomized before TKA surgery (N=60; 65% women [39]; mean age, 70.7±8.8y; weight, 77.8±11.3kg; size, 1.64±0.08m; body mass index, 29.9±4.1kg/m(2)). INTERVENTIONS: Participants received either 5 MLD treatments or a placebo, added to rehabilitation, in between the second day and the seventh day after surgery. MAIN OUTCOME MEASURES: Swelling was measured by blinded evaluators before surgery and at second day, seventh day, and 3 months using bioimpedance spectroscopy and volume measurement. Secondary outcomes were active and passive range of motion, pain, knee function, and gait parameters. RESULTS: At seventh day and 3 months, no outcome was significantly different between groups, except for the knee passive flexion contracture at 3 months, which was lower and less frequent in the MLD group (-2.6°; 95% confidence interval, -5.0° to -0.21°; P=.04; absolute risk reduction, 26.6%; 95% confidence interval, 0.9%-52.3%; number needed to treat, 4). The mean pain level decreased between 5.8 and 8.2mm on the visual analog scale immediately after MLD, which was significant after 4 of 5 MLD treatments. CONCLUSIONS: MLD treatments applied immediately after TKA surgery did not reduce swelling. It reduced pain immediately after the treatment. Further studies should investigate whether the positive effect of MLD on knee extension is replicable.

The Functions of Antioxidants and Heat Shock Proteins Are Altered in the Immune Organs of Selenium-Deficient Broiler Chickens.

Despite increasing evidence indicating the essential involvement of selenium (Se) in the immune system, the effect of Se deficiency on the regulation of oxidative stress and heat shock proteins (Hsps) in broiler chickens is still unclear. In the present study, we established an exudative diathesis (ED) broiler chicken model caused by Se deficiency. We then analyzed histological observations and detected the expression levels of Hsps and antioxidant indexes in immune tissues. The antioxidant function declined remarkably, and most of the Hsp expression levels increased significantly in the spleen, thymus, and bursa of Fabricius of the broiler chicks with ED (except the messenger RNA (mRNA) levels of Hsp27, Hsp40, and Hsp70, which decreased in thymus tissues from the treatment groups); therefore, constitutive oxidation resistance and higher Hsps in broiler chicks with ED caused defects in immune organ morphology and function, as evidenced by abnormal histological structures: red pulp broadening and lymphocytes in the cortex and medulla of the thymic lobule decreased distinctly and distributed loosely. These results underscore the importance of Se in establishing an immune organ microenvironment conducive to normal function.

Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil.

The present study was designed to assess the potential of supplementation of diet with Flaxseed (Linum usitatissimum, L.) oil (FXO), on obesity-related inflammation and reversal of obesity-induced insulin resistance. Swiss Albino mice, C57bl/6 mice and co-culture of 3T3-L1 adipocytes - RAW 264.7 macrophages to mimick obese adipose tissue environment were used for the study. Oral gavage of FXO at concentrations of 4, 8 or 16 mg/kg body weight (bwt) for 4 weeks or high-fat diet (HFD, 60% energy as fat) supplemented with dietary FXO (4, 8 or 16 mg/kg bwt) was given to the mice. FXO was characterised using gas chromatography - mass spectrometry. FXO supplemented HFD-fed mice (4 mg/kg bwt exhibited reduced adiposity index, serum glucose levels and triglycerides (8 and 16 mg/kg bwt) and improvement in insulin sensitisation (4, 8 and 16 mg/kg bwt) when compared with HFD mice. The co-culture showed a dose-dependent shift in cytokines towards anti-inflammatory (IL-4) state, with a decrease in pro-inflammatory TNF-α (p < 0.05). For immunomodulatory studies a dose-dependent increase (p < 0.05) was observed in antigen-specific levels of Th2 (IL-4) cytokine, serum anti-ova IgG1 and IgE levels. Suppression in anti-ova IgG2a, IgG2b, and IgG3 and antigen-specific Th1 cytokines like TNF-α and IFN-γ significantly (p < 0.05) was observed at 16 mg/kg bwt dosage. The results indicate that FXO exhibits an anti-inflammatory immunomodulatory potential and may partially relieve symptoms of obesity-associated insulin resistance.

Radiofrequency thermotherapy in the treatment of tongue base lymphoid hyperplasia: case report.

OBJECTIVE: This paper describes a case where a patient diagnosed with tongue base lymphoid hyperplasia was successfully treated with radiofrequency excision and interstitial radiofrequency-induced thermotherapy. CASE REPORT: A 53-year-old female presented with globus sensation, mild dysphagia, nocturnal breathing problems and 'hot potato voice' dysphonia. On flexible nasendoscopy, a visible tongue mass was seen to obstruct the posterior oropharynx. On magnetic resonance imaging scans, this mass looked suspicious of lymphoma, but on histology was confirmed to be benign reactive lymphoid hyperplasia. Sleep study findings indicated moderate obstructive sleep apnoea, with an apnoea-hypopnoea index of 18.1 events per hour. She was treated with radiofrequency-induced thermotherapy on three separate occasions. RESULTS: A post-operative sleep study showed a dramatic improvement in the patient's apnoea-hypopnoea index (3.8 events per hour). This correlated well with the improvement in her sleep quality and reduction of snoring. Over the follow-up period, there has been sustained resolution of dyspnoea, with almost total restoration of voice quality.

Caracterización clínico-epidemiológica de los linfomas en un período de cinco años en Villa Clara / Clinical and epidemiological characterization of lymphomas in a five year-period in Villa Clara

INTRODUCCIÓN: Los linfomas de Hodgkin y no Hodgkin son neoplasias malignas derivadas de los componentes celulares del sistema inmune, en particular, de los linfocitos y de sus precursores. Constituyen un grupo muy heterogéneo con amplias diferencias clinicobiológicas, pronósticas y terapéuticas. OBJETIVO: Caracterizar algunas variables clínico - epidemiológicas en los linfomas. MÉTODOS: Se realizó un estudio descriptivo y longitudinal entre enero de 2006 y diciembre de 2010 que incluyó a todos los pacientes adultos atendidos en los hospitales Celestino Hernández Robau y Arnaldo Milián Castro, en Santa Clara, Villa Clara. RESULTADOS: Se evaluaron 388 pacientes, con un predominio de edades mayores de 40 años, del sexo masculino y color de la piel blanca. El linfoma no Hodgkin tuvo mayor frecuencia; los factores de riesgo que predominaron fueron pertenecer al sexo masculino y la presencia del virus de Epstein-Barr. En las tres cuartas partes de los pacientes, la localización principal fue ganglionar. De las variedades histológicas del linfoma de Hodgkin la más frecuente fue la esclerosis nodular, mientras que para los linfomas no Hodgkin, fue el folicular. El estadio con mayor número de pacientes fue el III-b para ambos tipos de linfomas. La tercera parte de los pacientes fallecieron; el mayor número correspondió a los linfomas no Hodgkin. CONCLUSIÓN: Los linfomas tienen una alta morbilidad y mortalidad en los adultos de la provincia de Villa Clara.

IINTRODUCTION: Hodgkin and non-Hodgkin lymphomas are considered malignant neoplasms derived from cellular components of the immune system, in particular, of the lymphocytes and their precursors. They constitute a very heterogeneous group with broad clinical and biological, prognostic and therapeutic differences. OBJECTIVE: To characterize some clinical and epidemiological variables in lymphomas. METHODS: A descriptive and longitudinal study was carried out from January, 2006 to December, 2010, which included all adult patients who were attended at «Dr. Celestino Hernández Robau¼ and «Arnaldo Milián Castro¼ Hospitals, in Santa Clara, Villa Clara. RESULTS: A number of 388 patients were evaluated, with a predominance of white male, aged over 40. Non-Hodgkin lymphoma was the most frequent; male sex and the presence of Epstein-Barr virus were identified as predominant risk factors. The main localization of lymphomas was ganglionated in the three- quarter parts of patients. Nodular sclerosing was the most frequent histological variety of Hodgkin lymphomas, while for non-Hodgkin lymphomas it was follicular. The higher number of patients had III-b stage for both types of lymphomas. The third part of patients died; the higher number corresponded to non-Hodgkin lymphomas. CONCLUSION: Lymphomas has a high morbidity and mortality in adults from Villa Clara province.

Caracterización clínico-epidemiológica de los linfomas en un período de cinco años en Villa Clara / Clinical and epidemiological characterization of lymphomas in a five year- period in Villa Clara

Introducción: Los linfomas de Hodgkin y no Hodgkin son neoplasias malignas derivadas de los componentes celulares del sistema inmune, en particular, de los linfocitos y de sus precursores. Constituyen un grupo muy heterogéneo con amplias diferencias clinicobiológicas, pronósticas yterapéuticas. Objetivo: Caracterizar algunas variables clínico - epidemiológicas en los linfomas. Métodos: Se realizó un estudio descriptivo y longitudinal entre enero de 2006 y diciembre de 2010 que incluyó a todos los pacientes adultos atendidos en los hospitales Celestino Hernández Robau yArnaldo Milián Castro, en Santa Clara, Villa Clara. Resultados: Se evaluaron 388 pacientes, con un predominio de edades mayores de 40 años, del sexo masculino y color de la piel blanca. El linfoma no Hodgkin tuvo mayor frecuencia; los factoresde riesgo que predominaron fueron pertenecer al sexo masculino y la presencia del virus de Epstein-Barr. En las tres cuartas partes de los pacientes, la localización principal fue ganglionar. Delas variedades histológicas del linfoma de Hodgkin la más frecuente fue la esclerosis nodular, mientras que para los linfomas no Hodgkin, fue el folicular. El estadio con mayor número de pacientes fue el III-b para ambos tipos de linfomas. La tercera parte de los pacientes fallecieron; el mayor número correspondió a los linfomas no Hodgkin. Conclusión: Los linfomas tienen una alta morbilidad y mortalidad en los adultos de la provincia de Villa(AU)

Mutant USA strain of porcine circovirus type 2 (mPCV2) exhibits similar virulence to the classical PCV2a and PCV2b strains in caesarean-derived, colostrum-deprived pigs.

In 2012, a mutant porcine circovirus type 2 (mPCV2) strain was identified in cases of PCV-associated disease (PCVAD) in the USA. The mPCV2 had an additional amino acid, lysine (K), in the capsid at position 234. The objectives of this study were to compare the pathogenicity of mPCV2, PCV2a and PCV2b in pigs using biologically pure infectious virus stocks derived from respective infectious DNA clones, and to investigate the importance of genotype-specific ORF2 and the presence of lysine at position 234 of the capsid. A total of 47, 2-week-old, caesarean-derived, colostrum-deprived (CDCD) pigs were assigned to one of seven groups. At 3 weeks of age, the pigs were experimentally inoculated with saline, PCV2a, PCV2b, mPCV2, PCV2b-234-K (lysine addition in ORF2), chimeric PCV2b-ORF1/mPCV2-ORF2 or reciprocal chimeric mPCV2-ORF1/PCV2b-ORF2. All pigs were necropsied 21 days post-infection (p.i.). Gross lesions were limited to visible icterus and loss of body condition in a portion of the mPCV2 pigs. The amount of PCV2 DNA was significantly higher in pigs inoculated with mPCV2 compared with PCV2b in sera at 7 days p.i. and faecal swabs at 14 days p.i. Based on lymphoid lesions, a higher prevalence of PCVAD was seen in pigs infected with PCV2s containing the additional 234-K (64.3 %) compared with those infected with a PCV2 with the regular 233 bp ORF2 (40 %). Results indicated that all PCV2 isolates were capable of inducing severe lesions and disease in the CDCD pig model, and there was no significant difference in virulence.

Protective effects of Ligustrazine, Kakonein and Panax Notoginsenoside on the small intestine and immune organs of rats with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high mortality. It is important to study SAP complicated with multiple organ injury. In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine, Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus, spleen and lymph nodes) of rats with SAP and explored their mechanism of action. METHODS: One hundred forty-four rats with SAP were randomly divided into model control, Ligustrazine-treated, Kakonein-treated, and Panax Notoginsenoside-treated groups (n=36 per group). Another 36 normal rats comprised the sham-operated group. According to the different time points after operation, the experimental rats in each group were subdivided into 3-, 6- and 12-hour subgroups (n=12). At various time points after operation, the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were measured. RESULTS: Compared to the model control groups, the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different degrees. The serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 hours. The pathological severity scores for the small intestinal mucosa, thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group, for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group, and for the thymus (at 3 hours) and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control group. The pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein- and Panax Notoginsenoside-treated groups. CONCLUSIONS: All the three traditional Chinese drugs significantly alleviated the pathological changes in the small intestine and immune organs of SAP rats. Ligustrazine was the most effective one among them.

The gene expression profile of preclinical autoimmune arthritis and its modulation by a tolerogenic disease-protective antigenic challenge.

INTRODUCTION: Autoimmune inflammation is a characteristic feature of rheumatoid arthritis (RA) and other autoimmune diseases. In the natural course of human autoimmune diseases, it is rather difficult to pinpoint the precise timing of the initial event that triggers the cascade of pathogenic events that later culminate into clinically overt disease. Therefore, it is a challenge to examine the early preclinical events in these disorders. Animal models are an invaluable resource in this regard. Furthermore, considering the complex nature of the pathogenic immune events in arthritis, microarray analysis offers a versatile tool to define the dynamic patterns of gene expression during the disease course. METHODS: In this study, we defined the profiles of gene expression at different phases of adjuvant arthritis (AA) in Lewis rats and compared them with those of antigen mycobacterial heat shock protein 65 (Bhsp65)-tolerized syngeneic rats. Purified total RNA (100 ng) extracted from the draining lymph node cells was used to generate biotin-labeled fragment cRNA, which was then hybridized with an oligonucleotide-based DNA microarray chip. Significance analysis of microarrays was used to compare gene expression levels between the two different groups by limiting the false discovery rate to < 5%. Some of the data were further analyzed using a fold change ≥2.0 as the cutoff. The gene expression of select genes was validated by quantitative real-time PCR. RESULTS: Intriguingly, the most dramatic changes in gene expression in the draining lymphoid tissue ex vivo were observed at the preclinical (incubation) phase of the disease. The affected genes represented many of the known proteins that participate in the cellular immune response. Interestingly, the preclinical gene expression profile was significantly altered by a disease-modulating, antigen-based tolerogenic regimen. The changes mostly included upregulation of several genes, suggesting that immune tolerance suppressed disease by activating disease-regulating pathways. We identified a molecular signature comprising at least 12 arthritis-related genes altered by Bhsp65-induced tolerance. CONCLUSIONS: This is the first report of microarray analysis in the rat AA model. The results of this study not only advance our understanding of the early phase events in autoimmune arthritis but also help in identifying potential targets for the immunomodulation of RA.

IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of memory CD4(+) T cells in multiple tissues, especially at mucosal surfaces where most of these cells reside. Although antiretroviral therapy (ART) suppresses viral replication and promotes the recovery of peripheral CD4(+) T cells, HIV-infected patients fail to fully reconstitute the CD4(+) T-cell pool at mucosal sites. IL-15 has been shown to preferentially expand memory-phenotype T cells and promote their migration to nonlymphoid tissues. Here we examined IL-15 treatment in combination with highly active ART in chronically SIV-infected rhesus macaques and found that IL-15 delayed viral suppression and failed to enhance ART-induced total and antigen-specific CD4(+) T-cell reconstitution at mucosal and lymphoid sites. IL-15 was able to induce the transient proliferation of SIV-specific, CMV-specific, and total memory CD8(+) T cells, but not of SIV-specific or total CD4(+) T cells. Moreover, upon treatment interruption, macaques receiving combined IL-15+ART lost CD4(+) T cells faster than those receiving ART alone. These results suggest that the combination of IL-15 with highly active ART is not more efficient than ART alone in promoting CD4(+) T-cell recovery in HIV-infected individuals and may accelerate CD4+ T-cell loss after treatment interruption.

Fourteen-week toxicity study of green tea extract in rats and mice.

The toxicity of green tea extract (GTE) was evaluated in 14-week gavage studies in male and female F344/NTac rats and B6C3F1 mice at doses up to 1,000 mg/kg. In the rats, no treatment-related mortality was noted. In the mice, treatment-related mortality occurred in male and female mice in the 1,000 mg/kg dose groups. The cause of early deaths was likely related to liver necrosis. Treatment-related histopathological changes were seen in both species in the liver, nose, mesenteric lymph nodes, and thymus. In addition, in mice, changes were seen in the Peyer's patches, spleen, and mandibular lymph nodes. The no adverse effect level (NOAEL) for the liver in both species was 500 mg/kg. In the nose of rats, the NOAEL in males was 62.5 mg/kg, and in females no NOAEL was found. No NOAEL was found in the nose of female or male mice. The changes in the liver and nose were considered primary toxic effects of GTE, while the changes in other organs were considered to be secondary effects. The nose and liver are organs with high metabolic enzyme activity. The increased susceptibility of the nose and liver suggests a role for GTE metabolites in toxicity induction.

Effects of dexamethasone and Salvia miltiorrhizae on the small intestine and immune organs of rats with severe acute pancreatitis.

To observe the protecting effects and mechanisms of Dexamethasone and Salviae miltiorrhizae on intestinal mucosa and immune organs (spleen, thymus and lymph node) in rats with severe acute pancreatitis (SAP). The rats were randomly divided into sham-operated, model control, Dexamethasone treated group and Salviae miltiorrhizae treated group. At 3, 6 and 12 h after operation, the mortality rate, pathological changes of intestinal mucosa and immune organs as well as the contents of serum PAF, IL-1 beta and sIL-2R were observed, respectively. The mortality rate and the contents of PAF (at 3 and 6 h), IL-1 beta (at all time points) and sIL-2R (at 3 and 6 h) as well as the pathological scores of thymus (at all time points) and spleen (at 3 h) in Dexamethasone treated group were significantly lower than those in model control groups (P < 0.05). The contents of PAF (at 3 and 12 h), IL-1 beta (at 6 and 12 h) and sIL-2R (at 3 and 6 h) as well as the pathological scores of thymus (at all time points) and spleen (at 3 and 12 h) in Salviae miltiorrhizae treated group were markedly lower than those in model control groups (P < 0.05). Since both Dexamethasone and Salvia miltiorrhizae can reduce the contents of serum PAF, sIL-2R and IL-1 beta, mitigate the pathological changes in the small intestine, spleen and thymus and reduce the mortality rate of SAP rats, they show good therapeutic effects on SAP rats.