Tranilast treatment prevents chronic radiation-induced colitis in rats by inhibiting mast cells infiltration.

INTRODUCTION: Mast cells are the principal cells leading to acute and chronic colitis due to irradiation, radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups: control group (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). The rats in RG and TG were irradiated in the pelvic area (1.5cm from anus) with a single dose of 20 Gray under general anesthesia. Tranilast (100 mg/kg) was intraperitonially injected to mice of the TG for 10 days starting from the day of pelvic irradiation. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were evaluated histologically for the total inflammation score (TIS) and mast cell count. Expression of MUC2, MUC5AC and matrix metalloproteinase 9 (MMP9) were also assessed immunohistochemically. RESULTS: Both TIS and some components of TIS, epithelial atypia, vascular sclerosis and colitis cystica profunda (CCP) were significantly higher in RG than in TG (P=0.02, 0.038, 0.025, 0.01, respectively). The number of infiltrating mast cells was significantly higher in the RG than in TG (20, 3-54 and 6, 3-25, respectively, P=0.034). Quantitatively, the number of MMP9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (P<0.05). TIS and MMP9 exhibited strong associations (correlation coefficient r=0.56, P<0.05) Immunohistochemically, mucin-lake of CCP showed no staining for MUC5AX but positivity for MUC2. CONCLUSION: Tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC in association with the reduction of mast cell infiltration and MMP9 expression.

Cinnamaldehyde-Treated Bone Marrow Mesenchymal-Stem-Cell-Derived Exosomes via Aqueous Two-Phase System Attenuate IL-1ß-Induced Inflammation and Catabolism via Modulation of Proinflammatory Signaling Pathways.

Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1ß (IL-1ß) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1ß on chondrocytes. We stimulated chondrocytes with IL-1ß to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1ß on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1ß on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.

Polynucleotides Suppress Inflammation and Stimulate Matrix Synthesis in an In Vitro Cell-Based Osteoarthritis Model.

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin-1ß (IL-1ß) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL-1ß induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

Colonoscopy decreases mortality in colorectal cancer patients compared with fecal immunochemical test.

BACKGROUND AND AIM: Colonoscopy and fecal immunochemical test (FIT) are commonly used screening methods for the detection of colorectal cancer (CRC), but their effects on survival have not been compared. We compared survival outcomes in patients with CRC according to the exposure history to colonoscopy or FIT before diagnosis of CRC. METHODS: We performed a nationwide population-based retrospective cohort study using Korean national-insurance claims data. In total, 24 875 patients with CRC diagnosed in 2012 were included. The patients were divided into three groups in terms of examinations performed during the 10 years prior to CRC diagnosis: the colonoscopy group, the FIT group, and the never-screened group. Survival outcomes were compared among the three groups. The colonoscopy group and FIT group were matched using propensity score-matching method. RESULTS: The cohort consisted of 9619 patients in the colonoscopy group, 6936 patients in the FIT group, and 8320 patients in the never-screened group. The 5-year overall survival rates were 74.1% in the colonoscopy group, 65.9% in the FIT group, and 59.6% in the never-screened group (P < 0.001). The adjusted hazard ratios for death were 0.56 (95% confidence interval [CI], 0.53-0.59) in the colonoscopy group and 0.78 (95% CI, 0.74-0.82) in the FIT group compared with the never-screened group. In the matched cohort, the adjusted hazard ratios for death was 0.76 (95% CI, 0.72-0.81) in the colonoscopy group compared with the FIT group. CONCLUSION: Colonoscopy is a more effective method for reducing mortality in patients with CRC compared with FIT.

Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis.

Osteoarthritis (OA) is a low-grade inflammatory disorder of the joints that causes deterioration of the cartilage, bone remodeling, formation of osteophytes, meniscal damage, and synovial inflammation (synovitis). The synovium is the primary site of inflammation in OA and is frequently characterized by hyperplasia of the synovial lining and infiltration of inflammatory cells, primarily macrophages. Macrophages play a crucial role in the early inflammatory response through the production of several inflammatory cytokines, chemokines, growth factors, and proteinases. These pro-inflammatory mediators are activators of numerous signaling pathways that trigger other cytokines to further recruit more macrophages to the joint, ultimately leading to pain and disease progression. Very few therapeutic alternatives are available for treating inflammation in OA due to the condition's low self-healing capacity and the lack of clear diagnostic biomarkers. In this review, we opted to explore the immunomodulatory properties of mesenchymal stem cells (MSCs) and their paracrine mediators-dependent as a therapeutic intervention for OA, with a primary focus on the practicality of polarizing macrophages as suppression of M1 macrophages and enhancement of M2 macrophages can significantly reduce OA symptoms.

Hizikia fusiforme extract enhances dendritic cell maturation in vitro and in vivo.

Dendritic cells (DCs) are play critical roles in the priming and regulation of immune responses. DCs rapidly process and convey these antigens to prime antigen-specific T cells. Therefore, regulation of DCs functions is important for immunity and immunotherapies. Immune adjuvants for DCs activation are needed to improve the efficacy of vaccines against tumors and many infectious diseases. Therefore, we demonstrate that H. fusiformis extract can regulate DCs maturation and activation. H. fusiformis extract induced costimulatory molecules (CD 80 and CD86), antigen-presenting molecules (major histocompatibility complex (MHC) I and II), CCR7 expression, and interleukin (IL)-12 production in DCs. These effects are associated with upregulation of mitogen-activated protein kinase (MAPK) signaling pathway. In addition, H. fusiformis extract induces costimulatory molecules on splenic DCs and activated CD8+ T cells in vivo. Taken together, these findings suggest that H. fusiformis extract may be a potential efficient immune therapeutic compound in DCs-mediated immunotherapies. ABBREVIATIONS: CTL: cytotoxic T lymphocytes; DCs: dendritic cells; ERK: extracellular signal-regulated kinases; IL: interleukini; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MHC: major histocompatibility complex.

Stool-Based miR-92a and miR-144* as Noninvasive Biomarkers for Colorectal Cancer Screening.

OBJECTIVES: Current noninvasive screening tests for colorectal cancer (CRC) have insufficient sensitivity. MicroRNA (miRNA) levels in stool have potential as markers for noninvasive screening of CRC. We evaluated the diagnostic value of stool miRNA levels and determined the optimal miRNA subtypes for detecting CRC. METHODS: Stool samples were collected from 29 patients with CRC and 29 healthy controls. The stool levels of miR-21, miR-92a, miR-200c, miR-144*, miR-135a, miR-135b, miR-106a, and miR-17-3p were determined by real-time quantitative reverse transcription polymerase chain reaction. The sensitivity and specificity of the miRNAs for CRC were determined by receiver operating characteristics analysis. RESULTS: Among the eight tested miRNAs, the mean stool levels of miR-21, miR-92a, miR-144*, and miR-17-3p differed significantly between the CRC group and the control group (p =0.014, 0.001, <0.001, and 0.008, respectively). The sensitivities and specificities of miR-21, miR-92, miR-144*, and miR-17-3p were 79.3 and 48.3%, 89.7 and 51.7%, 78.6 and 66.7%, and 67.9 and 70.8%, respectively. In a multivariate analysis, miR-92a and miR-144* were significantly associated with the presence of CRC (p = 0.03 and 0.011, respectively). CONCLUSIONS: The stool levels of miR-92a and miR-144* showed good sensitivity and fair specificity for detection of CRC, and thus may be useful as noninvasive biomarkers for this disease.

Diagnostic value of magnetic resonance cholangiopancreatography to detect bile duct stones in acute biliary pancreatitis.

OBJECTIVES: This study aims to evaluate the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) in detecting common bile duct (CBD) stones in acute biliary pancreatitis (ABP). METHODS: The medical records of patients presenting with ABP from January 2008 to July 2013 were reviewed to assess the value of MRCP in detecting CBD stones in ABP. Endoscopic retrograde cholangiopancreatography (ERCP) was used as the reference standard to assess the diagnostic yield of MRCP in detecting choledocholithiasis. When ERCP was unavailable, intraoperative cholangiography or clinical follow-up was used as the reference standard. RESULTS: Seventy-eight patients who underwent MRCP were diagnosed with ABP, and thirty of the 78 patients (38%) were confirmed to have CBD stones per the study protocol. The sensitivity of MRCP in detecting CBD stones in ABP was 93.3% compared to 66.7% for abdominal CT (P < 0.008). The overall accuracy of MRCP in detecting choledocholithiasis was 85.9% compared to 74.0% for abdominal CT (P < 0.041). The area under the receiver operating characteristic curve (AUC) of MRCP in detecting CBD stones was 0.882, which was more accurate than the AUC of 0.727 for abdominal CT (P = 0.039). In 38 patients who underwent ERCP, the sensitivity and negative predictive value of MRCP in detecting CBD stones were both 100% regardless of the dilatation of the bile duct (≥7 mm versus < 7 mm). CONCLUSION: MRCP is an effective, noninvasive modality to detect CBD stones in ABP and can help identify patients who require ERCP.

Lymphocyte-to-monocyte ratio on day 7 is associated with outcomes in acute ischemic stroke.

The main features of stroke-induced immunosuppression are lymphopenia and deactivation of monocytes in peripheral blood. We hypothesized that lymphocyte-to-monocyte ratio (LMR) in peripheral blood may represent the degree of stroke-induced immunosuppression. To prove this hypothesis, we evaluated whether LMR is associated with risk of post-stroke infection and clinical outcome at 3 months in patients with acute ischemic stroke. We selected patients with stroke in anterior circulation within 24 h from onset. Peripheral blood sampling for differential blood count was performed on days 1 and 7. The LMRs on days 1 and 7 were analyzed to determine associations with excellent outcomes (modified Rankin Scale of score 0-1 at 3 months). One hundred and two patients were included. The initial National Institutes of Health Stroke Scale score (adjusted odd ratio [OR] 0.89; 95% confidence interval [CI], 0.83-0.95; P = 0.001) and LMR on day 7 (adjusted OR 1.49; 95% CI, 1.09-2.02; P = 0.011) were associated with excellent outcomes. LMRs on day 1 were significantly lower in stroke patients with pneumonia (P = 0.007) and pneumonia or urinary tract infection (P = 0.012) than those without infections. LMRs on day 7 were also significantly lower in stroke patients with infection (P = 0.005 in pneumonia, P = 0.003 in urinary tract infection, and P < 0.001 in pneumonia or urinary tract infection) than those without infections. Lower LMRs on day 7 are associated with worse outcomes at 3 months after stroke onset. LMR may be a useful marker for assessing the stroke-induced immunosuppression.

Clinical outcome of endoscopic management of duodenal Dieulafoy's lesions: endoscopic band ligation versus endoscopic hemoclip placement.

BACKGROUND: The most appropriate type of endoscopic hemostasis for bleeding due to duodenal Dieulafoy's lesions (DLs) is not yet established. The aim of this study was to assess the efficacy of mechanical endoscopic hemostasis for duodenal DLs and long-term outcome after successful hemostasis, as well as to compare the efficacy and safety of endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP). METHODS: Patients admitted to the emergency unit with acute upper gastrointestinal bleeding from duodenal DLs were enrolled in this study. The data were collected prospectively, but data analysis was performed retrospectively. Twenty-four patients with duodenal DLs were treated with EBL (n = 11) or EHP (n = 13). RESULTS: There were no significant differences between groups with respect to clinical or endoscopic characteristics, apart from the number of epinephrine (three cases with EBL vs. 11 cases with EHP; p = 0.011). Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient (9.1 %) from the EBL group and in five patients (38.5 %) from the EHP group (p = 0.166). The recurrent bleeding in the patient from the EBL group was treated by EHP. In the EHP group, all five patients achieved successful secondary hemostasis by endoscopic treatment (EBL in two patients and EHP in three patients). There were no differences in secondary outcomes between the two groups, including the number of endoscopic sessions required, need for angiographic embolization or emergent surgery, transfusion requirements, or length of hospital stay. No complications occurred, and there was no recurrence of bleeding in either group during the follow-up period. CONCLUSIONS: Mechanical endoscopic treatments are effective and safe for the treatment of bleeding duodenal DLs. A large-scale, randomized, controlled study is required to confirm the efficacy and safety of EBL and EHP for the management of bleeding duodenal DLs.

Circumferential submucosal incision prior to endoscopic mucosal resection provides comparable clinical outcomes to submucosal dissection for well-differentiated neuroendocrine tumors of the rectum.

BACKGROUND: Small rectal neuroendocrine tumors (NETs) can be treated with endoscopic resection. Endoscopic submucosal dissection (ESD) has been accepted as a reliable technique, but it is difficult. We evaluated the feasibility and efficacy of precut and endoscopic mucosal resection (CSI-EMR) for rectal NETs compared to ESD. METHODS: Patients with rectal NETs were enrolled consecutively. ESD or CSI-EMR was performed at operator's discretion. Histological and clinical outcomes were measured and compared between the two treatment modalities. RESULTS: Thirty-three patients were enrolled in the study. Seventeen NETs were treated by the ESD method and 16 were treated by CSI-EMR. Both groups had similar mean tumor diameters (ESD 7.53 ± 1.94 vs. CSI-EMR 6.63 ± 1.99 mm; p = 0.197). En bloc resection was achieved in 100 % of ESD group and 87.5 % of CSI-EMR group. Lateral margin involvement occurred in one patient in ESD group and two in CSI-EMR group. The histologically complete resection rate was 88.2 % (15 of 17) in the ESD group and 81.2 % (13 of 16) in CSI-EMR group (p = 0.592). One case of perforation occurred in both groups. Delayed bleeding did not occur. None of the measured outcomes were different between the two groups. Operating time was significant shorter in CSI-EMR group than in ESD group (9.69 vs. 20.12 min, respectively; p value = 0.004). CONCLUSIONS: CSI-EMR results in reliable clinical outcomes for small rectal NETs comparable to those of ESD. CSI-EMR is technically feasible and more time saving.

Comparison of prophylactic clip and endoloop application for the prevention of postpolypectomy bleeding in pedunculated colonic polyps: a prospective, randomized, multicenter study.

BACKGROUND AND STUDY AIMS: The effectiveness of the prophylactic clip for the prevention of postpolypectomy bleeding in pedunculated colonic polyps has not been confirmed. The aim of this prospective, randomized study was to compare the efficacy of prophylactic clip and endoloop application in the prevention of postpolypectomy bleeding in large pedunculated polyps. PATIENTS AND METHODS: A total of 195 patients who had pedunculated colorectal polyps, with heads ≥ 10 mm and stalks ≥ 5 mm in diameter, were included in the study between July 2010 and January 2013. Polyps were randomized to receive either clips or endoloops. Both devices were applied to the base of the stalk before conventional snare polypectomy. Bleeding complications were analyzed with a noninferiority margin of 5 %. RESULTS: A total of 203 polyps were included in the study (98 in the clip group and 105 in the endoloop group). Bleeding occurred after five polypectomies in the clip group (5.1 %) and after six in the endoloop group (5.7 %) (P = 0.847). Noninferiority of the prophylactic clip to the endoloop could not be confirmed (absolute bleeding rate difference - 0.6 %, 95 % confidence interval - 5.6 % to 6.8 %) due to small sample size. Immediate bleeding episodes occurred in 4/5 polyps in the clip group and 5/6 polyps in the endoloop group. Delayed bleeding occurred in one polyp in each group. CONCLUSIONS: These results suggest that the application of a prophylactic clip is as effective and safe as an endoloop in the prevention of postpolypectomy bleeding in large pedunculated colonic polyps. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01406379).

Exosomes Reshape the Osteoarthritic Defect: Emerging Potential in Regenerative Medicine-A Review.

Osteoarthritis (OA) is a joint disorder caused by wear and tear of the cartilage that cushions the joints. It is a progressive condition that can cause significant pain and disability. Currently, there is no cure for OA, though there are treatments available to manage symptoms and slow the progression of the disease. A chondral defect is a common and devastating lesion that is challenging to treat due to its avascular and aneural nature. However, there are conventional therapies available, ranging from microfracture to cell-based therapy. Anyhow, its efficiency in cartilage defects is limited due to unclear cell viability. Exosomes have emerged as a potent therapeutic tool for chondral defects because they are a complicated complex containing cargo of proteins, DNA, and RNA as well as the ability to target cells due to their phospholipidic composition and the altering exosomal contents that boost regeneration potential. Exosomes are used in a variety of applications, including tissue healing and anti-inflammatory therapy. As in recent years, biomaterials-based bio fabrication has gained popularity among the many printable polymer-based hydrogels, tissue-specific decellularized extracellular matrix might boost the effects rather than an extracellular matrix imitating environment, a short note has been discussed. Exosomes are believed to be the greatest alternative option for current cell-based therapy, and future progress in exosome-based therapy could have a greater influence in the field of orthopaedics. The review focuses extensively on the insights of exosome use and scientific breakthroughs centered OA.

Hyaluronic Acid Viscosupplement Modulates Inflammatory Mediators in Chondrocyte and Macrophage Coculture via MAPK and NF-κB Signaling Pathways.

Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by cartilage degeneration and synovial inflammation. Paracrine interactions between chondrocytes and macrophages play an essential role in the onset and progression of OA. In this study, in replicating the inflammatory response during OA pathogenesis, chondrocytes were treated with interleukin-1ß (IL-1ß), and macrophages were treated with lipopolysaccharide and interferon-γ. In addition, a coculture system was developed to simulate the biological situation in the joint. In this study, we examined the impact of hyaluronic acid (HA) viscosupplement, particularly Hyruan Plus, on chondrocytes and macrophages. Notably, this viscosupplement has demonstrated promising outcomes in reducing inflammation; however, the underlying mechanism of action remains elusive. The viscosupplement attenuated inflammation, showing an inhibitory effect on nitric oxide production, downregulating proinflammatory cytokines such as matrix metalloproteinases (MMP13 and MMP3), and upregulating the expression levels of type II collagen and aggrecan in chondrocytes. HA also reduced the expression level of inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 in macrophages, and HA exerted an overall protective effect by partially suppressing the MAPK pathway in chondrocytes and p65/NF-κB signaling in macrophages. Therefore, HA shows potential as a viscosupplement for treating arthritic joints.

Baicalin from Scutellaria baicalensis impairs Th1 polarization through inhibition of dendritic cell maturation.

Baicalin from Scutellaria baicalensis is a major flavonoid constituent found in the traditional Chinese medicinal herb Baikal skull cap. It has been widely used for the treatment of various diseases such as pneumonia, diarrhea, and hepatitis. Recent studies have demonstrated that baicalin possesses a wide range of pharmacological and biological activities, including anti-inflammatory, anti-microbial, anti-oxidant, and anti-tumor properties. Specifically, its anti-inflammatory activity has been estimated in various animal models of acute and chronic inflammation; however, its effects on dendritic cells (DCs) maturation and immuno-stimulatory activities are still unknown. In this study, we attempted to determine whether baicalin could influence DC surface molecule expression, antigen uptake capacity, cytokine production, and capacity to induce T-cell differentiation. Baicalin was shown to significantly suppress the expression of surface molecules CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II as well as the levels of interleukin-12 production in lipopolysaccharide stimulated DCs. Moreover, baicalin-treated DCs showed an impaired induction of the T helper type 1 immune response and a normal cell-mediated immune response. These findings provide important understanding of the immunopharmacological functions of baicalin and have ramifications for the development of therapeutic adjuvants for the treatment of DCs-related acute and chronic diseases.

18ß-Glycyrrhetinic acid from licorice root impairs dendritic cells maturation and Th1 immune responses.

18ß-Glycyrrhetinic acid (ß-GA) is a natural triterpenoid compound derived from licorice root. ß-GA has been demonstrated to exert antiviral and antitumor effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DCs) remain to be clearly elucidated. In this study, we attempted to determine whether ß-GA could influence DCs surface molecule expression, antigen uptake capacity, cytokine production and capacity to induce T-cell differentiation. The DCs used in this study were derived from murine bone marrow cells, and were used as immature or lipopolysaccharide (LPS)-stimulated mature DCs. The DCs were then assessed with regard to surface molecules expression, cytokine production, capacity to induce T-cell differentiation and proliferation. ß-GA was shown to significantly suppress the expression of surface molecules CD80, CD86, major histocompatibility complex (MHC) class I and MHC class II as well as the levels of interleukin-12 production in LPS-stimulated DCs. Moreover, ß-GA-treated DCs showed an impaired induction of the T helper type 1 immune response. These findings provide important understanding of the immunopharmacological functions of ß-GA and have ramifications for the development of therapeutic adjuvants for the treatment of DCs-related acute and chronic diseases.

Peptide derived from stromal cell-derived factor 1δ enhances the in vitro expression of osteogenic proteins via bone marrow stromal cell differentiation and promotes bone formation in in vivo models.

Mesenchymal stem cells (MSCs) rely on chemokines and chemokine receptors to execute their biological and physiological functions. Stromal cell-derived factor-1 (SDF-1) is upregulated in injury sites, where it acts as a chemotactic agent, attracting CXCR4-expressing MSCs, which play a pivotal role in the healing and regeneration of tissue throughout the body. Furthermore, SDF-1 expression has been observed in regions experiencing inflammation-induced bone destruction and fracture sites. In this study, we identified a novel peptide called bone-forming peptide-5 (BFP-5), derived from SDF-1δ, which can promote the osteogenesis of MSCs as well as bone formation and healing. Multipotent bone marrow stromal cells treated with BFP-5 showed enhanced alizarin red S staining and higher alkaline phosphatase (ALP) activity. Moreover, ALP and osterix proteins were more abundantly expressed when cells were treated with BFP-5 than SDF-1α. Histology and microcomputed tomography data at 12 weeks demonstrated that both rabbit and goat models transplanted with polycaprolactone (PCL) scaffolds coated with BFP-5 showed significantly greater bone formation than animals transplanted with PCL scaffolds alone. These findings suggest that BFP-5 could be useful in the development of related therapies for conditions associated with bones.