Mesenchymal stem cell secretome ameliorates over-expression of soluble fms-like tyrosine kinase-1 (sFlt-1) and fetal growth restriction (FGR) in animal SLE model.

INTRODUCTION: In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a "by-product" of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. MATERIALS AND METHODS: Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele's Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. RESULTS: The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; p < 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; p = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 ± 80.76 mg vs. 550 ± 64.03 mg; p < 0.001 and birth length: 14.43 ± 1.27 mm vs. 19.00 ± 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 ± 75.47 mg and 18.14 ± 1.34 mm, p = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; p = 0.794). CONCLUSIONS: Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.

Lacrimal Gland Histopathology and Secretory Function in Sjögren's Syndrome Mice Model Treated with Moringa oleifera Lam. Leaf Extract.

BACKGROUND: The pathogenesis of Sjögren's syndrome involves the activation of NF- κB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α, IL- 1ß, IL-6, IL-17, and interferon-γ. Through oxidative stress, they will cause necrosis and apoptosis of lacrimal gland cells, resulting in impaired secretory function or reduced tear production. Moringa oleifera leaf extract is known to have strong anti-inflammatory and antioxidant activities. OBJECTIVE: To determine the effect of Moringa oleifera leaf extract on lacrimal gland histopathology and secretory function in Sjögren's syndrome mice model. METHODS: The experimental study had a post-test only control group design with 32 eight-week-old male mice of the BALB/c strain divided into four groups, negative control (C-), which was not induced by SS, positive control (C+), treatment 1 (T1), and treatment 2 (T2) induced by Sjögren's syndrome by immunizing with the 60-kD Ro antigen (SSA) as much as 100 µg. After 42 days, the T1 group was given dexamethasone 1.23 mg/kg BW/day orally for 14 days, whereas T2 was given dexamethasone 1.23 mg/kg BW/day and Moringa oleifera leaf ethanol extract 200 mg/kg BW/day orally for 14 days. At the end of the study, lacrimal gland histopathology and secretory function (tear production) were examined. Statistical analysis using F ANOVA/Kruskal-Wallis was followed by partial difference test with the Least Significant Difference post hoc test/Mann-Whitney. Significant if p < 0.05. RESULTS: The comparison of lacrimal gland histopathology in T1 (p = 0.044) and T2 groups (p = 0.020) obtained significant results (p < 0.05) when compared to C+. However, the comparison of tear production in T1 (p = 0.127) and T2 groups (p = 0.206) was not significant (p > 0.05) when compared to the C+ group. CONCLUSION: The administration of Moringa oleifera leaf extract 200 mg/kg BW for 14 days could significantly improve lacrimal gland histopathology but was not effective in increasing tear production in Sjögren's syndrome mice model.

Platelet-rich fibrin as a tissue engineering material in accelerate bone healing in rat bone defects: A systematic review and meta-analysis.

Introduction: Various techniques for tissue engineering have been introduced to help regenerate damaged or lost bone tissue. This study aimed to see the potential implication of platelet-rich fibrin (PRF) to accelerate the bone healing process in rat bone defects. Methods: A systematic literature search was conducted from several electronic databases on subjects looking at the use of PRF in rat bone defects and their results in bone regeneration. Specific results compared PRF vs. other methods, PRF vs. control, and PRV vs. combination PRF and other methods. Science Direct, PubMed, and Cochrane Library were the main information sources. The Cochrane Collaboration method is employed to assess the risk of bias. Results: A total of 483 rats were used in the twelve studies, and this meta-analysis showed that the PRF vs. other methods pooled odds ratio (OR) obtained was 0.92 (95% CI 0.42-2.04; p = 0.29; I2 = 18%), PRF versus control OR obtained 9.45 (95% CI 4.68-19.08; P = 0.01; I2 = 0%), the combination of PRF compared to PRF alone OR obtained 0.12 (95% CI 0.03-0.41; p = 0.01; I2 = 0%). Discussion: Platelet-rich fibrin accelerates the bone healing process in rat bone defects compared to physiologically. Platelet-rich fibrin combined with other methods can stimulate rat bone defects than utilization of platelet-rich fibrin only. The small number of articles assessed may cause limitations in sensitivity tests. This study was registered in the research registry (reviewregistry1341).

Brazilin Isolated from Caesalpina Sappan Wood Induces Intrinsic Apoptosis on A549 Cancer Cell Line by Increasing p53, caspase-9, and caspase-3.

OBJECTIVE: Lung cancer is the leading cause of death among cancer patients. The majority of lung cancer is the Non-Small Lung Carcinoma (NSLC). This study evaluated the potency of brazilin isolated from Caesalpinia sappan wood to induce apoptosis on non-small lung carcinoma cell line, A549, by examining the expression of p53, caspase-9, and caspase-3. METHODS: Brazilin was isolated from Caesalpinia sappan wood following a guided assay and it was determined by using Brazilin®SIGMA as standard. The activity of brazilin on the growth of A549 cell line was analysed by MTT assay and the apoptosis was evaluated by flowcytometer following Annexin V (FITC) and PI staining. The expression of p53, caspase-9, and caspase-3 was examined by immunocytochemistry. RESULT: The IC50 of brazilin on A549 cell line was 43µg/mL. Cell treatment with 20 µg/mL and 40 µg/mL of brazilin significantly increased early apoptosis (p<0.001). Cell treatment with 40 µg/mL  of Brazilin significantly increased late apoptosis (p<0.001). Brazilin significantly increased the expression of p53, Caspase-9, and caspase-3 (p<0.001). CONCLUSION: This study showed evidence of the activity of brazilin to induce intrinsic apoptosis on a NSLC cell line A549.

Case report: Transformation of juvenile fibroadenoma to borderline phyllodes tumor in young lady.

INTRODUCTION: Fibroadenoma is the most common benign tumor found in young women. Transformation for Fibroadenoma to borderline phyllodes tumor is rare. Phyllodes tumor tends to recur locally due to the aggressive nature of the phyllodes tumor tissue, which tends to become malignant when recurrence occurs. PRESENTATION OF CASE: We report an 18-year-old woman with a lump in the right breast for one year, a mass in the upper lateral quadrant measuring 20x15x10cm; the lump felt mobile, supple, cystic. 2 years earlier, lumpectomy surgery with anatomical pathology of fibroadenoma mammae with 6 cm. A biopsy was performed, the result was a borderline phyllodes tumor. Neoadjuvant chemotherapy was performed with tumor reduction >50%, followed by wide excision surgery with tumor-free margins. The first one-year evaluation showed no signs of recurrence, and no signs of distant metastases were found. CONCLUSION: Our patient had a juvenile relapse FA which progressively changed to borderline tumor phyllodes borderline. We report this case to the need for continuous follow-up for fibroadenoma cases and the possibility of recurrence and becoming malignant.

Improvement in inflammation and airway remodelling after acupuncture at BL13 and ST36 in a mouse model of chronic asthma.

BACKGROUND: Asthma is a chronic inflammatory disease that affects millions of people worldwide. Chronic asthma is commonly resistant to steroid therapy. Acupuncture has an anti-inflammatory effect and has been widely used as an add-on therapy for asthma. OBJECTIVE: To evaluate the effects of acupuncture on the inflammatory response and airway remodelling in the bronchioles of an asthma mouse model. METHODS: A chronic asthma model was produced in female BALB/c mice by ovalbumin (OVA) sensitisation. 32 mice were randomised into four groups: control; asthma (OVA); OVA+BL13; and OVA+BL13+ST36. OVA was administered by intraperitoneal injection on days 0 and 14 followed by aerosol exposure of 1% OVA three times a week for 6 weeks. Manual acupuncture (MA) was performed three times a week for 6 weeks at BL13 alone, or BL13 in combination with ST36, in the two MA-treated groups. At the end of the experiment, blood samples were collected to determine eosinophil and neutrophil counts and lung tissue was prepared for histological examination. RESULTS: A pronounced reduction in the neutrophil count was achieved after MA at BL13+ST36 (P=0.005) while the eosinophil count was lowered after MA both at BL13 (P=0.007) and BL13+ST36 (P=0.006). Reduction in the bronchiolar epithelial and smooth muscle thickness and the number of goblet cells was observed after MA at BL13 (P=0.001, P=0.001 and P=0.002, respectively) and BL13+ST36 (P=0.001, P=0.002 and P=0.001, respectively). CONCLUSION: Acupuncture can reduce the inflammatory response and prevent airway remodelling in a chronic asthma mouse model.