Intranasal delivery of mesenchymal stem cells (MSCs) to the olfactory bulb is a promising approach for treating olfactory injury. Additionally, using the homing phenomenon of MSCs may be clinically applicable for developing therapeutic cell carriers. Herein, using superparamagnetic iron oxide nanoparticles (SPIONs) and a permanent magnet, we demonstrated an enhanced homing effect in an olfactory model. Superparamagnetic iron oxide nanoparticles with rhodamine B (IRBs) had a diameter of 5.22 ± 0.9 nm and ζ-potential of +15.2 ± 0.3 mV. IRB concentration of 15 µg/mL was injected with SPIONs into MSCs, as cell viability significantly decreased when 20 μg/mL was used (p ≤ 0.005) compared to in controls. The cells exhibited magnetic attraction in vitro. SPIONs also stimulated CXCR4 (C-X-C chemokine receptor type 4) expression and CXCR4-SDF-1 (Stromal cell-derived factor 1) signaling in MSCs. After injecting magnetized MSCs, these cells were detected in the damaged olfactory bulb one week after injury on one side, and there was a significant increase compared to when non-magnetized MSCs were injected. Our results suggest that SPIONs-labeled MSCs migrated to injured olfactory tissue through guidance with a permanent magnet, resulting in better homing effects of MSCs in vivo, and that iron oxide nanoparticles can be used for internalization, various biological applications, and regenerative studies.

Recently, obstetric massive transfusion protocols have shifted toward early intervention. This study aimed to develop a prediction model for transfusion of ≥5 units of packed red blood cells (PRBCs) during cesarean section in women with placenta previa. We conducted a cohort study including 287 women with placenta previa who delivered between September 2011 and April 2018. Univariate and multivariate logistic regression analyses were used to test the association between clinical factors, ultrasound factors, and massive transfusion. For the external validation set, we obtained data (n=50) from another hospital. We formulated a scoring model for predicting transfusion of ≥5 units of PRBCs, including maternal age, degree of previa, grade of lacunae, presence of a hypoechoic layer, and anterior placentation. For example, total score of 223/260 had a probability of 0.7 for massive transfusion. Hosmer-Lemeshow goodness-of-fit test indicated that the model was suitable (p>0.05). The area under the receiver operating characteristics curve (AUC) was 0.922 [95% confidence interval (CI) 0.89-0.95]. In external validation, the discrimination was good, with an AUC value of 0.833 (95% CI 0.70-0.92) for this model. Nomogram calibration plots indicated good agreement between the predicted and observed outcomes, exhibiting close approximation between the predicted and observed probability. We constructed a scoring model for predicting massive transfusion during cesarean section in women with placenta previa. This model may help in determining the need to prepare an appropriate amount of blood products and the optimal timing of blood transfusion.

Seong Jin Choi, M.D., Jieun Kang, M.D., and Young Uh, M.D.. Ann Lab Med 2021;41:380-5. https://doi.org/10.3343/alm.2021.41.4.380

Serum creatinine level (SCr) typically decreases during pregnancy due to physiologic glomerular hyperfiltration. Therefore, the clinical practice of estimated glomerular filtration rate (eGFR) based on SCr concentrations might be inapplicable to pregnant women with kidney disease since it does not take into account of the pregnancy-related biological changes. We integrated the Wonju Severance Christian Hospital (WSCH)-based findings and prior knowledge from big data to reveal the relationship between the abnormal but hidden SCr level and adverse pregnancy outcomes. We analyzed 4004 pregnant women who visited in WSCH. Adverse pregnancy outcomes included preterm birth, preeclampsia, fetal growth retardation, and intrauterine fetal demise. We categorized the pregnant women into four groups based on the gestational age (GA)-unadjusted raw distribution (Q1–4_raw), and then GA-specific (Q1–4_adj) SCr distribution. Linear regression analysis revealed that Q1-4_adj groups had better predictive outcomes than the Q1–4_raw groups. In logistic regression model, the Q1–4_adj groups exhibited a robust non-linear U-shaped relationship with the risk of adverse pregnancy outcomes, compared to the Q1–4_raw groups. The integrative analysis on SCr with respect to GA-specific distribution could be used to screen out pregnant women with a normal SCr coupled with a decreased renal function.

αKlotho is a type 1 transmembrane anti-aging protein. αKlotho-deficient mice have premature aging phenotypes and an imbalance of ion homeostasis including Ca²⁺ and phosphate. Soluble αKlotho is known to regulate multiple ion channels and growth factor-mediated phosphoinositide-3-kinase (PI3K) signaling. Store-operated Ca²⁺ entry (SOCE) mediated by pore-forming subunit Orai1 and ER Ca²⁺ sensor STIM1 is a ubiquitous Ca²⁺ influx mechanism and has been implicated in multiple diseases. However, it is currently unknown whether soluble αKlotho regulates Orai1-mediated SOCE via PI3K-dependent signaling. Among the Klotho family, αKlotho downregulates SOCE while βKlotho or γKlotho does not affect SOCE. Soluble αKlotho suppresses serum-stimulated SOCE and Ca²⁺ release-activated Ca²⁺ (CRAC) channel currents. Serum increases the cell-surface abundance of Orai1 via stimulating vesicular exocytosis of the channel. The serum-stimulated SOCE and cell-surface abundance of Orai1 are inhibited by the preincubation of αKlotho protein or PI3K inhibitors. Moreover, the inhibition of SOCE and cell-surface abundance of Orai1 by pretreatment of brefeldin A or tetanus toxin or PI3K inhibitors prevents further inhibition by αKlotho. Functionally, we further show that soluble αKlotho ameliorates serum-stimulated SOCE and cell migration in breast and lung cancer cells. These results demonstrate that soluble αKlotho downregulates SOCE by inhibiting PI3K-driven vesicular exocytosis of the Orai1 channel and contributes to the suppression of SOCE-mediated tumor cell migration.

Sarcopenia is defined as an age-related loss of skeletal muscle and is associated with several health disorders. Causes of sarcopenia, which included physical inactivity, alcohol, dietary habits, and smoking, have been researched. The present study was undertaken to examine the association between reproductive span and sarcopenia in Korean women. Data obtained from 2008 to 2011 Korea National Health and Nutrition Examination Surveys (KNHANES) were analyzed. We defined sarcopenia based on the cut-off values of the Foundation for the National Institutes of Health (FNIH) sarcopenia project criteria: ASM/BMI < 0.512 for women. Reproductive span was defined as years from menarche to menopause, and we divided the 3970 study subjects into three groups by reproductive span tertile. Multivariate logistic regression analysis was used to determine adjusted ORs for the relation between reproductive span and sarcopenia. The prevalence of sarcopenia in the study was 17.7% (704 of 3970). Multiple logistic regression analysis was performed using weighted populations. After adjusting for covariates, reproductive span was found to be inversely associated with the risk of sarcopenia [Tertile 1 = 1 (reference); Tertile 2, odds ratio (OR) = 0.927, 95% confidence interval (CI) = 0.863–0.995; Tertile 3, OR = 0.854, 95% CI = 0.793–0.915].