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Background: Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD., Objective: In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats., Methods: The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis., Results: ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFβ. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats., Conclusion: Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats., Competing Interests: There are no conflict of interest., (© 2023 Brama Ihsan Sazli, Dharma Lindarto, Refli Hasan, Agung Putra, Agung Pranoto, Rosita Juwita Sembiring, Syafruddin Ilyas, Santi Syafril.)

Background: In myocardial infarction (MI), inflammatory cytokine including tumor necrosis factor-α (TNF-α) plays pivotal role throughout worsening processes and recovery, whereas its cleavage is controlled by a disintegrin and metalloproteinases-17 (ADAM-17). Syzygium polyanthum (Wight) is widely used plant in Indonesia and Southeast Asian countries to treat various illnesses., Objective: This study aimed to analyze the effect of S. polyanthum extract towards TNF-α and ADAM17 expressions in MI rat model., Methods: Myocardial infarction were surgically induced in wistar rats by ligating left anterior descending coronary artery in both treatment and control group. Around 3.6 mg of S. polyanthum extract (SPE) was administered via nasogastric tube to treatment groups, while control group received only saline. Serum TNF-α level and expression of TNF-α and ADAM17 in blanching heart muscle was examined in both groups on day 1, day 4, day 7, and day 14 after treatment with SPE., Results: Reduction of serum TNF-α levels was markedly seen from day 4 in treatment group and was lower than in control group since day 4. Expression of ADAM17 was reduced and expression of TNF-α was only seen in myocardial membrane in group with SPE treatment., Conclusion: Syzygium polyanthum exerts its anti-inflammatory effect by decreasing ADAM17 expression subsequently lowering TNF-α regulation in MI rat model., Competing Interests: None declared., (© 2020 Refli Hasan, Gontar Alamsyah Siregar, Dharma Lindarto.)