BACKGROUND: Patient with larger ischemic lesion will suffer more severe neurogical deficit. The utility of MRI for lesion size measurement is still limited, therefore additional approach was pursued through examination of markers released by damaged brain cell, GFAP and S100B protein. The aim of this study is to know whether both markers are associated with the neurological deficit of anterior circulation ischemic stroke. METHODS: This observational prospective study enrolled 74 patients with anterior circulation ischemic stroke diagnosis. GFAP and S100B protein were measured with ELISA using blood collected at 48 to 72 hours after onset. The neurological deficit was assessed with NIHSS ad discharged.RESULTS: There was a significant association between GFAP level and discharged NIHSS (p=0.008) with 100% sensitivity and 100% negative predictive value. S100B protein also showed a significant correlation with discharged NIHSS (r=0.488; p=0.000) and this correlation could be described with an equation (OR=1.009; 95% CI=1.0003-1.0188; p=0.044). S100B protein at 78.3215 ng/L would give true prediction as 73.9% (95% CI=62.7%-85.2%, p=0.001). CONCLUSIONS: GFAP and S100B protein that were measured at 48 to 72 hours after onset were significantly associated with NIHSS at discharge. KEYWORDS: GFAP, S100B protein, discharged NIHSS, ischemic stroke

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40–80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors.

Background . Obesity is expected to hinder efferocytosis due to ADAM17‐mediated cleavage of the MER tyrosine kinase receptor, producing soluble MER (sMER) that disrupts MERTK binding to cell death markers. However, the intracellular efferocytosis pathway in central obesity remains elusive, particularly the role of low‐grade chronic inflammation in its initiation and identification of binding signals that disrupt efferocytosis. Objective . We investigate the efferocytosis signaling pathway in men with central obesity and its relationship with inflammation, cell death, and related processes. Methods . A cross‐sectional study was conducted, and clinical data and blood samples were collected from 56 men with central obesity (obese group) and 29 nonobese individuals (control group). Clinical evaluations and predefined biochemical screening tests were performed. The efferocytosis signaling pathway was investigated by measuring phosphatidylserine (PS), ADAM17, TNF‐alpha (TNF‐ α ), and sMER. Results . Metabolic syndrome was detected in more than half of the participants in the obese group according to the predefined tests. Mean levels of PS, TNF‐ α , and sMER were higher in the obese group but not significantly different from those of the control group. Further analysis based on waist circumference (WC) ranges in the obese group revealed a significant increase in PS and sMER levels between the control group and the obese group with WC greater than 120 cm. ADAM17 levels were significantly higher in the obese group than in the control group. PS was positively correlated with WC and ADAM17. ADAM17 was positively correlated with TNF‐ α and sMER, indicating impaired efferocytosis. Conclusions . Central obesity appeared to cause a disturbance in efferocytosis that began with cell damage and death, along with an enlargement of the WC and an ongoing inflammatory response. Efferocytosis was disrupted by proinflammatory cytokine regulators, which induced the production of sMER and interfered with the efferocytosis process.

Background: S100B protein and glial fibrillary acidic protein (GFAP) released during ischemia have been associated with stroke. This study aimed to know whether there was a correlation between the concentration of these markers with the severity of neurological deficit in ischemic stroke. Methods: This was a cross-sectional study, which involved 143 ischemic stroke patients who were admitted to hospital not more than 72 hours after the onset and fulfilled the criteria. The concentration of S100B protein and GFAP was determined by ELISA method. Blood level of S100B and GFAP in patient with mild, moderate, and severe stroke were analyzed with Kruskal-Wallis test. Results: There was a significant difference between S100B protein concentration among subjects with mild (median 63.31 ng/L), moderate (median 88.93 ng/L), and severe (median 511.55 ng/L) NIHSS at admission (p < 0.05). A weak significant correlation was found between the severity of NIHSS and the S100B protein concentration. The more severe the NIHSS, the higher the S100B protein concentration (r = 0.351; p < 0.001). Subjects with moderate and severe NIHSS were more frequent to have an intermediate or high level of S100B protein than the subjects with mild NIHSS (OR = 3.9; p < 0.001). The median concentration of GFAP was significantly higher in severe NIHSS subjects (median 0.374 ng/mL) than its concentration in mild (median 0.047 ng/mL) and moderate (median 0.043 ng/mL) NIHSS subjects (p < 0.05). Conclusion: S100B protein concentration was significantly higher in linier relation with the severity of NIHSS, while the GFAP concentration was significantly higher if the NIHSS had been already severe. (Med J Indones. 2013;22:215-20. doi: 10.13181/mji.v22i4.602) Keywords: GFAP, ischemic stroke, NIHSS, S100B protein

Diabetes mellitus (DM) is a chronic endocrine and metabolic disease indicated by the presence of hyperglycemia. It has been known that hyperglycemia and oxidative stress are the main culprit of all DM complications, including macrovascular complications. As a byproduct of lipid, protein, and carbohydrate metabolism, methylglyoxal (MGO) is a highly reactive substance which plays a positive signaling role in helping cells regain redox balance under oxidative stress circumstances. DM-related problems lead to an excess of mitochondrial superoxide in the heart and big and small vascular endothelial cells. Elevated intracellular reactive oxygen species induce impaired angiogenesis in reaction to ischemia, trigger several proinflammatory pathways, and result in enduring epigenetic modifications that propel the continuous expression of proinflammatory genes even after glucose levels return to normal. Over time, the significance of the extremely quick advanced glycation end-products (AGE) production caused by the extremely reactive MGO has been clarified. It is now evident that MGO causes vascular tissue to react maladaptively. Glyoxalase 1 (GLO1) is the primary enzyme in an organism's enzymatic glyoxalase defense mechanism, which converts MGO to D-lactate in order to counteract the harmful effects of MGO. Understanding the role of the MGO–GLO1 pathway in the etiology of vascular disease in diabetes has advanced significantly. Therefore, it can be summarized that vascular damage are linked to diabetes. The AGE precursor MGO are important in determining the connection between diabetes and vascular damage. MGO and AGEs play a role in several phases of the development of diabetes complications. MGO and AGEs may be useful therapeutic targets for diabetes's macrovascular problems.KEYWORDS: hyperglycemia, AGE, methylglyoxal, glyoxalase, D-lactate, gluthatione, oxidative stress.

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine–metabolic disorder with chronic low-grade inflammation and insulin resistance (IR). Elevated C-peptide, a marker of compensatory hyperinsulinemia and reduced adiponectin, an insulin-sensitizing adipokine, contribute to the metabolic dysregulation observed in PCOS. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) and their secretome have immunomodulatory properties via paracrine and epigenetic mechanisms, yet longitudinal evidence in PCOS is limited. Methods: This randomized controlled trial (RCT) involved 40 women with PCOS (Rotterdam criteria) who were randomly assigned to four treatment groups: (1) metformin 750 mg/day, (2) UC-MSC infusion (0.3 million cells/kg body weight), (3) secretome (nasal drops, 2 mL), and (4) a combination of UC-MSC (0.3 million cells/kg body weight) and secretome (nasal drops, 2 mL). Parameters measured included fasting glucose, fasting insulin, HOMA-IR, C-peptide, and adiponectin at baseline and at months 1, 3, and 6. Analysis was performed using repeated-measures ANOVA or Friedman test, and ROC curves were used to evaluate the predictive value of biomarkers on therapy response. Results: All participants completed the 6-months of follow-up. The secretome group demonstrated a significant increase in fasting glucose (month 1: p = 0.013; month 3: p = 0.007; month 6: p = 0.032), as well as an increase in adiponectin in the UC-MSC group (month 6: p = 0.016). The combination of UC-MSC and secretome induced early metabolic modulation, characterized by transient reductions in adiponectin at months 1 and 3 (p = 0.022 and p = 0.013, respectively) and early increases in insulin-related parameters; however, these effects were not sustained at month 6. ROC analysis showed that glucose, insulin, and C-peptide variables had low discriminatory ability (AUC < 0.5), while adiponectin showed a trend of increasing predictive value for improving insulin sensitivity. Conclusions: Combination therapy with UC-MSCs and secretome may have potential to improve metabolic profiles through increasing adiponectin and improving insulin sensitivity in PCOS patients, especially in the group with insulin resistance. MSC-based approaches are not only symptomatic but also have the potential to restore ovarian function through immunomodulatory and epigenetic mechanisms.