CP-25 alleviates antigen-induced experimental Sjögren's syndrome in mice by inhibiting JAK1-STAT1/2-CXCL13 signaling and interfering with B-cell migration.

The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjögren's syndrome (ESS) with paeoniflorin-6'-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model.

Characteristics of laboratory indexes in COVID-19 patients with non-severe symptoms in Hefei City, China: diagnostic value in organ injuries.

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.

Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma.

Background: Insulin-like growth factor binding protein-2 (IGFBP2) levels are significantly increased in the plasma of hepatocellular carcinoma (HCC) patients. However, the correlation between IGFBP2 levels and clinical parameters and the exact role of IGFBP2 in HCC are unclear. In this study, we identified the role and potential molecular mechanisms of IGFBP2 in HCC.

Abnormal polarization of macrophage-like cells in the peripheral blood of patients with glioma.

Glioma is a type of malignant tumor arising from glial cells of the brain or the spine. Circulation-derived macrophage infiltration is a characteristic of the glioma microenvironment. The polarization status of circulation-derived macrophages in patients with glioma remains unclear.

Emerging role of targeting macrophages in rheumatoid arthritis: Focus on polarization, metabolism and apoptosis.

Macrophages maintain a dynamic balance in physiology. Various known or unknown microenvironmental signals influence the polarization, activation and death of macrophages, which creates an imbalance that leads to disease. Rheumatoid arthritis (RA) is characterized by the massive infiltration of a variety of chronic inflammatory cells in synovia.

Long non-coding RNAs in ovarian granulosa cells.

Granulosa cells (GCs) are somatic cells surrounding oocytes within follicles and are essential for folliculogenesis. Pathological changes in GCs are found in several ovarian disorders. Recent reports have indicated that long non-coding RNAs (lncRNAs), which modulate gene expression via multiple mechanisms, are key regulators of the normal development of GCs, follicles, and ovaries.

Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA.

Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-B Signaling Pathway in Rheumatoid Arthritis.

Objective: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells.

Methods: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry.

Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future.

The ontogeny of macrophages in most organs has already been established. Owing to the limited number and inaccessibility of synovial macrophages (SMs), the origin of SMs has not been fully elucidated. Previous studies suggested that SMs have two major origins, namely, tissue-resident and monocyte-derived SMs.

The genetic sequence, origin, and diagnosis of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019, which was found to be associated with a large seafood and animal market in Wuhan. Airway epithelial cells from infected patients were used to isolate a novel coronavirus, named the SARS-CoV-2, on January 12, 2020, which is the seventh member of the coronavirus family to infect humans. Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV.

Genetic correction of Werner syndrome gene reveals impaired pro-angiogenic function and HGF insufficiency in mesenchymal stem cells.

WRN mutation causes a premature aging disease called Werner syndrome (WS). However, the mechanism by which WRN loss leads to progeroid features evident with impaired tissue repair and regeneration remains unclear. To determine this mechanism, we performed gene editing in reprogrammed induced pluripotent stem cells (iPSCs) derived from WS fibroblasts.

Paeoniflorin-6'-O-benzene sulfonate down-regulates CXCR4-Gβγ-PI3K/AKT mediated migration in fibroblast-like synoviocytes of rheumatoid arthritis by inhibiting GRK2 translocation.

Objective: This study aims to explore the effect of paeoniflorin-6'-O-benzene sulfonate (CP-25) on the migration of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and the mechanism focused on CXCR4-Gβγ-PI3K/AKT signaling.

Methods: Human synovial tissues were collected from RA and osteoarthritis (OA) patients. Immunohistochemistry (IHC) and Western blot were used to detect the protein expression of CXCR4, GRK2, Gβγ, PI3K, p-PI3K, AKT and p-AKT.

Combined PGE2 with TNF-α promotes laryngeal carcinoma progression by enhancing GRK2 and TRAF2 interaction.

TNF-α has been confirmed to promote tumor growth in LSCC. PGE2 expression in LSCC tissues was significantly higher than in tumor-adjacent tissues. In the present work, we aimed to discover the combined role of TNF-α and PGE2 in LSCC progression and its potential mechanisms.

CP-25 inhibits PGE2-induced angiogenesis by down-regulating EP4/AC/cAMP/PKA-mediated GRK2 translocation.

G protein-coupled receptor kinase 2 (GRK2), a type of cytosolic enzyme, transiently translocates to the plasma membrane upon G protein-coupled receptors (GPCRs) activation, and it also binds to extracellular signal-regulated kinase (ERK) to inhibit the activation of ERK. GRK2 deficiency in endothelial cells (ECs) leads to increased pro-inflammatory signaling and promotes recruitment of leukocytes to activated ECs. However, the role of GRK2 in regulating angiogenesis remains unclear.

Alleviating effect of paeoniflorin-6'-O-benzene sulfonate in antigen-induced experimental Sjögren's syndrome by modulating B lymphocyte migration via CXCR5-GRK2-ERK/p38 signaling pathway.

Primary Sjögren's syndrome (pSS) is an autoimmune disease of unresolved aetiology that affects the exocrine glands. Clinical symptoms frequently also involve skin, liver, kidney and neurovascular components. The pathogenesis of pSS is still unclear but B cell hyperactivity has been identified as a hallmark of pSS.

Low dose of emetine as potential anti-SARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokinetic evidences.

Unlabelled: The global pandemic of COVID-19 has attracted extensive drug searching interets for the new coronavirus SARS-CoV-2. Although currently several of clinically used "old" drugs have been repurposed to this new disease for the urgent clinical investigation, there is still great demand for more effective therapies for the anti-infections. Here we report the discovery that an "old" drug Emetine could potently inhibit SARS-CoV-2 virus replication and displayed virus entry blocking effect in Vero cells at low dose.

Tolerogenic Dendritic Cells Generated by BAFF Silencing Ameliorate Collagen-Induced Arthritis by Modulating the Th17/Regulatory T Cell Balance.

Tolerogenic dendritic cells (tolDCs) have received much attention because of their capacity to restore immune homeostasis. RNA interference techniques have been used in several studies to generate tolDCs by inactivating certain molecules that regulate DC maturation and immunologic function. BAFF is a key B cell survival factor that is not only essential for B cell function but also T cell costimulation, and DCs are the major source of BAFF.

Circulating tumor DNA/circulating tumor cells and the applicability in different causes induced hepatocellular carcinoma.

In 2015, liquid biopsy was rated one of the top 10 breakthrough technologies of the year by MIT Technology Review. Liquid biopsy is a type of in vitro diagnostic method involving a noninvasive blood test. It is also a breakthrough technology used to detect tumors and cancers and assist in therapeutic strategies.

GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice.

Rheumatoid arthritis (RA) is characterized by the massive infiltration of various chronic inflammatory cells in synovia. In synovial fluid of patients with RA, M1 macrophages are dominant among all subtypes of macrophages, the mechanisms of macrophages polarization imbalance in RA has not been fully illuminated. The prostaglandin E2 (PGE2) augments M2 polarization in part via the cyclic adenosine monophosphate (cAMP)-cyclic AMP responsive element binding (CREB) signaling.

The emerging role of long non-coding RNAs in tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are an important cellular component of the tumor microenvironment (TME) and play an essential role in tumor immunity. Recently, numerous studies have indicated that long non-coding RNAs (lncRNAs) can affect several functions of TAMs. In the present review, we summarize the versatile role of lncRNAs in the polarization, epigenetic modulation, and classic signaling pathways of TAMs, which represent a potential target for tumor diagnosis or treatment.

Murine models of psoriasis and its applications in drug development.

Psoriasis is an autoimmune skin disease which characteristic of a well-demarcated, erythematous, raised lesion with silvery-white dry scale. Although the mechanism of psoriasis has not been fully understood so far, much progress has been made in understanding many of its complex potential mechanism, particularly the crucial role of the IL-23/Th17 axis. There are a large number of psoriasis models that reflect the complexity of the psoriasis mechanisms.

CP-25 exerts anti-angiogenic effects on a rat model of adjuvant-induced arthritis by promoting GRK2-induced downregulation of CXCR4-ERK1/2 signaling in endothelial cells.

Angiogenesis can produce an invasive and destructive front, also named a pannus, comprised of inflammatory vascular tissue that covers and erodes articular cartilage, subchondral bone and peri‑articular soft tissues in rheumatoid arthritis (RA). Paeoniflorin‑6'‑O‑benzene sulfonate (CP‑25) is a novel ester derivative of paeoniflorin. We previously demonstrated that CP‑25 exerts anti‑inflammatory and immunoregulatory effects.

Multiple roles of microRNA-146a in immune responses and hepatocellular carcinoma.

MicroRNAs (miRNAs/miRs), consisting of ~22 nucleotides of single-stranded RNA, participate in post-transcriptional gene regulation by binding to the 3'-untranslated region (UTR) of mRNAs, repressing their translation and promoting their degradation. Studies have shown that certain miRNAs play a key role in the control of various cellular activities, such as inhibiting inflammation, modulating cell differentiation and suppressing cancer growth. The role of miR-146a in the immune response and in the pathogenesis of hepatocellular carcinoma (HCC) has also been investigated.