OBJECTIVES: This study aimed to explore the therapeutic effect and mechanism of ginsenoside Rb3 on experimental periodontitis and bone resorption in rats. METHODS: Male SD rats were randomly divided into a control group, a ligation group, an Rb3 group, and a doxycycline (Dox) group for in vivo experiments. A periodontitis model was established by ligating the maxillary second molar, and samples were collected after 3 weeks of drug treatment. Micro-CT assessment of alveolar bone resorption was performed, and hematoxylin-eosin (HE) staining was used to observe pathological changes in periodontal and visceral tissues. Tartrate resistant acid phosphatase (TRAP) staining was applied to detect the formation of osteoclasts in periodontal tissues, and enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum levels of interleukin (IL)-6, IL-8, immunoglobulin (Ig)M, and IgG. Quantitative polymerase chain reaction (qPCR) was employed to detect the expression of factors related to gingival inflammation and osteoclast formation. Immunofluorescence staining was used to detect phospho-extracellular signal-regulated kinase (p-ERK) expression. In vitro experiments were conducted by pretreating RAW264.7 cells with drugs and adding lipopolysaccharides (LPS) stimulation from Porphyromonas gingivalis (P. gingivalis). IL-1β and IL-6 mRNA expression was detected by qPCR, and Western blot was used to detect the effect of Rb3 on the mitogen-activated protein kinases (MAPKs) signaling pathway. RESULTS: Compared with the control group, the ligation group showed significant periodontitis and bone resorption. Compared with the ligation group, the Rb3 group showed a decrease in alveolar bone resorption and osteoclast formation; p-ERK/ERK ratio, IL-1β, IL-6, and nuclear factor of activated T cells (NFATc1) mRNA levels and downstream gene expression in periodontal tissues; serum IL-6, IL-8, IgG, and IgM levels. Rb3 reduced IL-8 and IL-1β mRNA expression levels and p-ERK/ERK and p-p38 MAPK/p38 MAPK ratios in RAW264.7 cells induced by P. gingivalis LPS stimulation. CONCLUSIONS Rb3 inhibits inflammation and bone resorption in experimental periodontitis in rats. Compared with Dox, Rb3 has better effects in inhibiting pro-inflammatory factors and osteoclast gene expression and may exert anti-inflammatory effects by activating the MAPK signaling pathway.
Animals ; Ginsenosides/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Periodontitis/pathology* ; Rats ; Osteoclasts/drug effects* ; Interleukin-1beta/metabolism* ; Interleukin-6/blood* ; Mice ; Alveolar Bone Loss ; Interleukin-8/blood* ; Immunoglobulin G/blood* ; RAW 264.7 Cells ; Transcription Factors

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
Humans ; Castleman Disease/pathology* ; Plasma Cells/pathology* ; Immunoglobulin G4-Related Disease ; China ; Lymphadenopathy/pathology* ; Inflammation/pathology* ; Lymph Nodes/pathology* ; Diagnosis, Differential ; Lymphadenitis/pathology* ; Immunoglobulin G/metabolism*

PURPOSE: To report a case of immunoglobulin G4 (IgG4)-related ophthalmic disease associated with adult xanthogranulomatous disease. CASE SUMMARY: A 38-year-old male with a history of cholecystectomy visited our clinic for bilateral periorbital swelling. Histopathology of the orbital biopsy showed diffuse infiltration of foamy histiocytes with Touton giant cells and lymphoid follicles, with a diagnosis of adult-onset xanthogranuloma. After excisional biopsy, he was treated with azathioprine and prednisolone. Four years after treatment, he again visited the clinic due to bilateral, yellowish eyelid masses. Serological examinations were all nonspecific findings, except for elevation of IgG and IgG4 levels. Magnetic resonance imaging showed bilateral symmetric soft tissue enlargement with slightly heterogeneous T1/T2 isosignal intensity, with contrast enhancement at the superolateral aspect of extraconal spaces. Excisional biopsy and blepharoplasty were performed. Immunohistochemical sections showed that the IgG4+/IgG plasma cell ratio was 10–20% and the IgG4 plasma cell count was 22/high power field (HPF). His past sections of 2013 from the pathology department were again stained and showed that the IgG4+/IgG plasma cell ratio was 40–50% and the IgG4 plasma cell count was 59/HPF. Thus, he was definitely diagnosed with IgG4-related ophthalmic disease. CONCLUSIONS: If there is recurrent eyelid swelling, IgG4-related ophthalmic disease should be considered as a differential diagnosis. And the patient with adult xanthogranulomatous disease can be diagnosed with IgG4-related ophthalmic disease.
Adult ; Azathioprine ; Biopsy ; Blepharoplasty ; Cholecystectomy ; Diagnosis ; Diagnosis, Differential ; Eyelids ; Giant Cells ; Histiocytes ; Humans ; Immunoglobulin G ; Immunoglobulins ; Magnetic Resonance Imaging ; Male ; Orbit ; Pathology ; Plasma Cells ; Prednisolone

OBJECTIVETo study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).

METHODSSprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.

RESULTSGastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).

CONCLUSIONOur findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Gastric Mucosa ; pathology ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 7 ; metabolism ; Precancerous Conditions ; drug therapy ; pathology ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism ; Staining and Labeling ; Stomach Neoplasms ; drug therapy ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

To investigate the function and regulation mechanism of ATP-binding cassette, subfamily G, member 2 (ABCG2) in retinoblastoma cancer stem cells (RCSCs), a long-term culture of RCSCs from WERI-Rb1 cell line was successfully established based on the high expression level of ABCG2 on the surface of RCSCs. To further explore the molecular mechanism of ABCG2 on RCSCs, a microRNA that specifically targets ABCG2 was predicted. Subsequently, miR-3163 was selected and confirmed as the ABCG2-regulating microRNA. Overexpression of miR-3163 led to a significant decrease in ABCG2 expression. Additionally, ABCG2 loss-of-function induced anti-proliferation and apoptosis-promoting functions in RCSCs, and multidrug resistance to cisplatin, carboplatin, vincristine, doxorubicin, and etoposide was greatly improved in these cells. Our data suggest that miR-3163 has a significant impact on ABCG2 expression and can influence proliferation, apoptosis, and drug resistance in RCSCs. This work may provide new therapeutic targets for retinoblastoma.
3' Untranslated Regions ; ATP Binding Cassette Transporter, Sub-Family G, Member 2/antagonists & inhibitors/genetics/*metabolism ; Antagomirs/metabolism ; Antineoplastic Agents/toxicity ; Apoptosis/drug effects ; Base Sequence ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Gene Silencing ; Humans ; MicroRNAs/antagonists & inhibitors/genetics/*metabolism ; Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism ; Neoplastic Stem Cells/*metabolism ; Retinoblastoma/metabolism/pathology ; Sequence Alignment ; Transfection

OBJECTIVETo study the prevalence of IgG4-positive plasma cells in Rosai-Dorfman disease and to assess the association between Rosai-Dorfman disease and IgG4-related sclerosing disease (IgG4-SD).

METHODSThe clinicopathologic features of 12 tissue samples of Rosai-Dorfman disease (11 extranodal and one nodal) from nine patients were reviewed. The degree of fibrosis and occlusive phlebitis was studied by HE staining. The expression of IgG4 and IgG in plasma cells were studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system.

RESULTSNine tissue samples showed different degree of fibrosis (four tissue samples were mild, one tissue sample was moderate and four tissue samples were severe) and two tissue samples showed occlusive phlebitis in the lesional tissue. Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (> 50 per high-power field) in four tissue samples, moderate infiltration (30 to 50 per high-power field) in two tissue samples, mild (10 to 29 per high-power field) in three cases and negative infiltration (< 10 per high-power field) in three tissue samples (P < 0.01). Three tissue samples fulfilled the diagnostic criteria of IgG4-SD (> 50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including one tissue sample each of Rosai-Dorfman disease in the left facial skin, above the left eye socket, and in the right parotid.

CONCLUSIONSSome cases of Rosai-Dorfman disease fulfill the diagnostic criteria and show the histologic features of IgG4-SD. They may represent members of the IgG4-SD spectrum. The detection of IgG4-positive plasma cells in the lesional tissues of Rosai-Dorfman disease may have clinical pathological significance.

Fibrosis ; Histiocytosis, Sinus ; diagnosis ; immunology ; Humans ; Immunoglobulin G ; chemistry ; Immunohistochemistry ; Phlebitis ; pathology ; Plasma Cells ; chemistry

Immunoglobulin G4-related disease (IgG4-RD) is an emerging immune-mediated fibro-inflammatory disorder which can involve any organ. The main characteristics of IgG4-RD are increased serum IgG4 concentration, abundant IgG4+ plasma cells in affected tissues, and painless swollen organs often without general symptoms. Typical pathology features of IgG4-RD are lymphoplasmacytic infiltration, dense storiform fibrosis, and obliterative pheblitis. The pathogenesis of IgG4-RD remains elusive, but involvement of excess production of type 2 T helper cells, regulatory T-cell cytokines, and B-cell activating factor in the development of IgG4-RD has been suggested. Diagnosis of IgG4-RD can be made on the basis of serological, imaging, particularly histopathological findings. Glucocorticoid is the first-line therapy for patients with multiple organ dysfunction and clinical symptoms. Drugs such as azathioprine, mycophenolate mofetil, methotrexate, and cyclophosphamide can be used as steroid-sparing agents. Rituximab is reported to be an effective therapy for treatment of IgG4-RD, even without concomitant glucocorticoid therapy. This review summarizes current concepts on pathophysiology, clinical manifestations, and treatment of IgG4-RD.
Azathioprine ; B-Cell Activating Factor ; Cyclophosphamide ; Cytokines ; Diagnosis ; Fibrosis ; Humans ; Immunoglobulin G ; Immunoglobulins* ; Methotrexate ; Pathology ; Plasma Cells ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Rituximab

IgG4-related disease (IgG4-RD) is a newly recognized disease entity. IgG4-RD is characterized by a single or multiple masses in one or more organs; a lymphoplasmacytic infiltrate with a high percentage of plasma cells within the lesion staining for IgG4; a peculiar pattern of fibrosis known as "storiform" fibrosis; and elevated serum IgG4 concentrations. IgG4-RD can occur in various organs, including pancreas, kidneys, lungs, retroperitoneum, and prostate gland. The head and neck involvements of IgG4-RD have been chiefly described in Mikulicz disease (MD), Küttner's tumor, orbital? inflammatory pseudotumor, and idiopathic hypertrophic pachymeningitis (IHP) previously. Recent studies reported that IgG4-RD could also involve ear, nose and throat. Here we reviewed the literatures about ear, nose and throat involvement by IgG4-RD, in order to provide some theoretical bases for the diagnosis and treatment of IgG4-RD.
Autoimmune Diseases ; physiopathology ; Ear ; physiopathology ; Fibrosis ; Humans ; Immunoglobulin G ; Nose ; physiopathology ; Pharynx ; physiopathology ; Plasma Cells ; pathology

IgG4-related disease (IgG4-RD) is characterized by a systemic involvement of tumor-like lesions with IgG4-positive plasmacytes. We experienced a case of IgG4-RD developed in a patient with bronchial asthma (BA) and chronic rhinosinusitis (CRS). A 55-yr-old female patient with BA and CRS complained of both eyes and neck swelling as well as a recurrent upper respiratory infection in recent 1 yr. The serum levels of IgG4, creatinine, and pancreatic enzymes were elevated. A biopsy of the submandibular gland showed an abundant infiltration of IgG4-positive plasmacytes. Her symptoms remarkably improved after the treatment of a systemic steroid that has been maintained without recurrence. We report a rare case of IgG4-RD developed in a patient with BA and CRS.
Asthma/complications/*diagnosis ; Chronic Disease ; Creatinine/blood ; Female ; Humans ; Immunoglobulin G/*blood ; Middle Aged ; Pancreas/enzymology ; Plasma Cells/physiology ; Prednisolone/therapeutic use ; Republic of Korea ; Rhinitis/complications/*diagnosis/drug therapy ; Sinusitis/complications/*diagnosis/drug therapy ; Submandibular Gland/pathology ; Tomography, X-Ray Computed