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Aim Studies have shown that SARS-Cov-2 has the ability to activate proinflammatory cytokine leading to acute inflammation. During the SARS-Cov-2 infection, an increase of the secretion of production TNF-α in seen in COVID-19 patients along with a decrease in anti-inflammatory cytokine IL-10, and growth factor TGF-β caused cytokine storm and damaged tissues. Alpinia galanga extract contains several secondary metabolites with strong antiinflammation and antioxidant effect. The aim of this study was to evaluate the effect of Alpinia galanga extract on peripheral blood mononuclear cells (PMBC) acute inflammation cells model stimulated with TNF-α. Methods Alpinia galanga was extracted under maceration methods on ethanol 96%. The PMBC was collected from three healthy humans and isolated using ficol reagent and cultured with the TNF-α 100pg/mL for 72 h. The TNF-α levels were evaluated under ELISA reader. Furthermore, the IL-10 and TGF-β gene expression was analysed using qRT-PCR after 24 h treatment with Alpinia galanga extract. Results Alpinia galanga extract has no cytotoxic effect on Vero cells with IC50 value of >1000µg/mL. The PBMC acute inflammation cells model stimulated by TNF-α 100pg/mL, after 72 h induction the PBMC cells significantly expressed a high level of TNF-α up to 341±10.87 pg/mL. Furthermore, the treatment of Alpinia galanga significantly increased the anti-inflammatory cytokine IL-10 and growth factor TGF-β in dose dependent manner. Conclusion These findings suggested that Alpinia galanga extract has strong antiinflammation activity. [ABSTRACT FROM AUTHOR]

Aim To determine the effect of hypoxic mesenchymal stem cells (MSCs) on the interleukin (IL)-10 and interferon (IFN)-gamma in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Methods This study used a post-test control group design. Hypoxic MSCs were isolated and characterized according to their surface marker expression and differentiation capacities. PBMCs isolated from SLE patients were divided into three groups: control and two treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with a ratio of 1:10 (T1) and 1:1 (T2) for 48 h incubation. Furthermore, IFN-gamma and IL-10 levels were determined by cytometric bead array (CBA) flow cytometry. Results Hypoxic MSCs significantly decreased the IFN-gamma levels and increased the IL-10 levels in dose-dependent manner compared to the control group. The highest activity of hypoxic MSCs was noticed in T2 group. Conclusion Hypoxic MSCs- induced IL-10 are important in the control of anti-inflammatory effect on SLE through inhibiting IFN-gamma. [ABSTRACT FROM AUTHOR]

Aim Allergic rhinitis (AR) is an IgE-mediated inflammation of the nose. Regulatory T cells (Tregs), plasma cells and inflammatory cytokines have shown to play a critical role in allergic airway inflammation. The aim of the study was to investigate the role of mesenchymal stem cells (MSCs) in generating Treg cells and plasma cells associated with regulating interlukin-10 (IL-10) in AR model. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and MSCs treatment group). Ovalbumin (OVA) nasal challenge was conducted daily from day 15 to 21, and MSCs (1x106 ) were administrated intraperitoneally to OVA-sensitized rats on day 21. Sneezing was observed from day 24 to 27. The rats were sacrificed on day 24 and day 27. The expression of Treg and plasma cells was analysed by flow cytometry assay. The level of IL-10 was analysed under ELISA assay. Results This study showed that the percentage of sneezing and rubbing times significantly decreased in MSCs treatment associated with the regulation of IL-10 level and plasma cell. This finding was aligned with the significant increase of Treg level. Conclusion MSCs administration regulates IL-10 and plasma cell-mediated immune and inflammatory responses while increasing Treg cell production. MSCs may be a promising therapeutic target for treating Treg-mediated allergic diseases. [ABSTRACT FROM AUTHOR]

Aim To determine the effect of red algae extract on the gene expression of catalase and caspase-3 in testicules of rats induced by boric acid (BA). Methods This is experimental research with post-test control group design. Twenty four healthy male Wistar rats were divided into four treatment groups: a healthy group, negative control group, two treatment groups with red algae extract 400mg/kgBW/day (T1) and red algae extract 800mg/kgBW/day (T2). Each group was treated with BA 500mg/kgBW/day for 14 days, whereas the healthy group did not receive BA. In the treatment groups T1 and T2 were given red algae extract for 14 days. On day 15 all treatment groups were terminated and catalase and caspase-3 gene expression were analysed using qRT-PCR. Results In the healthy group, the expression of the catalase gene was 1.39±0.67 and the expression of the caspase-3 gene was 1.06±0.17. In the negative control group, there was a significant decrease in catalase gene expression, 0.68±0.27 (p<0.05), and a significant increase in caspase-3 gene expression, 5.71±2.47 (p<0.05). Treatment groups T1 and T2 showed a significant increase in catalase gene expression, 2.67±0.69; and 2.85±0.64, respectively (p<0.05) and caspase-3, 3.96±1,16 and 1.89±0.84, respectively, compared to the control group. Conclusion: The administration of red algae extract had a significant effect on increasing the expression of the catalase gene and decreasing the expression of the caspase-3 gene. This suggests that red algae extract has the potential to be developed as a protective agent against exposure to the effects of BA. [ABSTRACT FROM AUTHOR]

Aim To determine the effect of secretome hypoxia mesenchymal stem cells (SH-MSCs) on the relative gene expression of hypoxia inducible factor-1a (HIF-1a) and basic fibroblast growth factor (bFGF) in accelerating histomorphometric repair of tendon to bone interface healing in rats acute rotator cuff tear (RCT) model. Methods This is experimental research with posttest control group design. Thirty-male Wistar rats were divided into five treatment groups: healthy group and rotator cuff reconstruction group included four groups: SH-MSCs W2 (the treatment group was given a SH-MSCs 0.5 mL and terminated at weeks 2), NaCl W2 (the control vehicle group was assigned NaCl 0.5 mL and terminated at weeks 2), SH-MSCs W8 (the treatment group was given a SHMSCs 0.5 mL and terminated at weeks 8), and NaCl W8 (the control vehicle group was given NaCl 0.5 mL and terminated at weeks 8). All the rats were terminated on day termination and HIF-1a and bFGF gene expression were analysed using qRT-PCR. Results SH-MSCs significantly increased the HIF-1a and bFGF gene expression than the NaCl group even in week 2 and week 8. The highest increased gene expression of HIF-1a and bFGF was on week 8. Conclusion SH-MSCs are important in the healing repair process of the tendon-to-bone interface in acute RCT model rats through increasing gene expression of HIF-1α and bFGF. [ABSTRACT FROM AUTHOR]

Aim Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation of the pancreatic islets of Langerhans. Hyperglycaemia leads to suppressed antioxidant enzyme and increased inflammation in the pancreatic cell, resulting in pancreatic cell death. Hypoxic secretome mesenchymal stem cells (HS-MSCs) are soluble molecules secreted by MSCS that have the antiinflammation ability by secreting various cytokines including IL-10 and TGF-β which potent as a promising therapeutic modality for T1DM. This study aims to investigate the role of HS-MSCs in regulating superoxide dismutase (SOD) and caspase-3 gene expression in T1DM model. Methods Twenty male Wistar rats (6 to 8 weeks old) were randomly divided into four groups (sham, control, HS-MSCs 0.5 mL and HS-MSCs 1 mL intraperitoneal treatment group). Streptozotocin (STZ) 60mg/kgBB was conducted once on day 1, HS-MSCs 0.5mL (T1) and HS-MSCs 1 mL (T2) were administrated intraperitoneally on day 7, 14, and 21 after STZ administration. The rats were sacrificed on day 28; the gene expression of SOD and IL-6 was analysed by qRT-PCR. Results This study showed that the ratio of SOD significantly increased in HS-MSCs treatment associated with suppression of IL-6 gene expression. Conclusion HS-MSCs administration suppresses oxidative stress and inflammation by up regulating SOD and inhibiting IL-6 to control T1DM. [ABSTRACT FROM AUTHOR]

Aim Triple negative breast cancer cells (TNBC) are the population of breast cancer cells that are responsible for cancer recurrence and apoptosis resistance. Unfortunately, current therapies have limited efficacy to TNBC population due to apoptosis resistance and chemoresistance. Tumour suppressor p53 and survivin are primary targets for TNBC therapy. Consequently, a search for a natural compound which targets p53 and survivin is needed to further advance TNBC treatment. Curcuma longa extract (CL), a natural compound induces apoptosis in several cancer cells by targeting various molecules and possess fewer side effects. However, a possible potential of CL as p53- and survivin modulating agent in TNBC cells has not been investigated. Methods MDAMB-231 cells were treated with several concentration of CL, after which, viability, p53 gene expression, surviving protein expression, and caspase-3 protein expression were evaluated. Results After 24-h treatment, CL possessed cytotoxic effect with IC50 value of 13 μg/mL. Treatment with 1.625, 3.25, 6.5, and 13 μg/mL of CL resulted in 2.70-25.80% increase in caspase-3 expression levels followed by 94.60 – 21.60% decrease in survivin protein levels. CL induced remarkably p53 gene expression ratio up to 5-fold at 13 μg/mL. Survivin protein levels were inversely proportional to p53 accumulation levels. Low survivin protein levels combined with high levels of p53 accumulation were correlated to higher apoptotic rates. Conclusion p53 and survivin as molecular targets of CL contribute to caspase-3-dependent apoptosis in TNBC cells and this compound represents an attractive p53- and survivin modulating agent in TNBC. [ABSTRACT FROM AUTHOR]

Aim Allergic rhinitis (AR) is a heterogeneous condition that has been associated with inflammatory responses and is characterized by clinical typical symptoms of nasal itching, sneezing, watery discharge and congestion. Mesenchymal stem cells (MSCs) are multipotent stem cells that have the immunoregulatory ability by secreting various cytokines which potent as a promising therapeutic modality for allergic airway diseases, including AR. The aim of this study was to investigate the effect of rat UC-MSCs on the number of mast cells, the expression of Hsp70 indicated by the nasal symptoms allergic, particularly nasal rubbing in ovalbumininduced AR rats. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and OVA+MSCs group). OVA nasal challenge was conducted daily from day 15 to 21, and UC-MSCs (1x106 ) were administrated intraperitoneally to OVA-sensitized rats on day 21. Nasal rubbing was observed from day 22 to 28. The rats were sacrificed on day 22 and day 28. The nasal cavity tissues were prepared for histological observations. Results The administration of UC-MSCs could reduce the number of mast cells and the expression of Hsp70 leading to reduction of nasal symptoms allergic, particularly nasal rubbing. Conclusion Based on this finding, MSCs present a promising immediate curative effect to the inflammatory reaction in AR rats. [ABSTRACT FROM AUTHOR]

Aim Mesenchymal stem cells (MSCs) have potent immunosuppressive properties to control systemic lupus erythematosus (SLE) disease by inhibiting indoleamine 2,3-dioxygenase (IDO), and increasing regulatory T cells (Treg) to control innate and adaptive immune cells. However, the interaction and mechanism regarding IDO and B cells in the co-culture of MSC and SLE peripheral blood mononuclear cell (PBMCs) remain unclear. This study aimed to investigate the effects of MSCs in controlling B cells through IDO expression in PBMC of SLE patients. Methods This study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups: sham, control, and three treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with a ratio of 1:10, 1:25, and 1:40 for 72 h incubation. The B cell levels were analysed by flow cytometry with cytometric bead array (CBA) and the IDO levels were determined by ELISA. Results The percentages of B cells decreased significantly in groups treated by dose-dependent MSCs, particularly in T1 and T2 groups. These findings were aligned with the significant decrease of the IDO level. Conclusion MSCs control B cells-mediated by a decrease of IDO in PBMC of SLE patients. [ABSTRACT FROM AUTHOR]