TSPO Modulates IL-4-Induced Microglia/Macrophage M2 Polarization via PPAR-γ Pathway

Microglia activation has been reported to be associated with pathogenesis of neuroinflammation, central nervous system damage, and degeneration diseases. With various damage-associated molecules released, M1 polarization of microglia emerges early after injury and followed by M2 polarization. In this study, we demonstrate using a primary microglia polarization model that, during the M2 polarization of microglia, the protein expression of translocator protein (TSPO) was decreased and peroxisome proliferator–activated receptor (PPAR-γ) activation was observed. In addition, we found TSPO antagonist PK11195 treatment enhanced PPAR-γ expression in M2-polarized microglia, while TSPO agonist FGIN-1-27 and TSPO overexpression in microglia significantly suppressed PPAR-γ expression in both the cytoplasm and nucleus. Then, real-time quantitative PCR was used to detect the expression of M2 polarization markers in microglia after TSPO ligand treatment, the data showed that PK11195 promoted the expression of CD206, Arg-1, YM-1, and FIZZ-1 induced by interleukin-4 (IL-4), and FGIN-1-27 and TSPO overexpression inhibited the expression of these molecules. Furthermore, the release of BDNF, CNTF-1, IGF-1, and NGF-1 from microglia was determined by enzyme-linked immunosorbent assay; these trophic factors showed similar trends with expression of M2 polarization markers. Levels of BDNF, CNTF-1, IGF-1, and NGF-1 were obviously upregulated by PK11195 and downregulated by FGIN-1-27 and TSPO overexpression. We propose that IL-4 in the hypoxic ischemia brain site induces the M2 polarization of microglia, and TSPO inhibits the M2 polarization and trophic factor release through PPAR-γ pathway.     

Aluminum-induced “mixed” cell death in mice cerebral tissue and potential intervention

Neurotoxicity Research - The brain is one of organs vulnerable to aluminum insult. Aluminum toxicity is involved in neurobehavioral deficit, neuronal cell dysfunction, and death. The aim of this...     

Population pharmacokinetics of vactosertib,a new TGF-β receptor type Ι inhibitor,in patients with advanced solid tumors

Cancer Chemotherapy and Pharmacology - Vactosertib, a novel inhibitor of transforming growth factor-β type Ι receptor, is under development for the treatment of various cancers. The...     

Difference between bone age at the hand and elbow at the onset of puberty

In the pubertal period, bone age advances rapidly in conjunction with growth spurts. Precise bone-age assessments in this period are important, but results from the hand and elbow can be different. We aimed to compare the bone age between the hand and elbow around puberty onset and to elucidate the chronological age confirming puberty onset according to elbow-based bone age.A total of 211 peripubertal subjects (127 boys and 84 girls) who underwent hand and elbow radiographs within 2 months was enrolled. Two radiologists and a pediatric orthopedic surgeon assessed bone age. Hand bone age was graded using the Greulich–Pyle (GP) method, and elbow bone age was determined using the Sauvegrain method. The correlation of 2 methods was evaluated by Demining regression analysis, and the mean absolute difference (MAD) with chronological age was compared between pre-pubertal and pubertal subjects. Receiver-operating characteristic curve analysis was performed to determine the chronological age confirming puberty onset.There was a statistically significant difference in bone age revealed by the GP and Sauvegrain methods in the pubertal group. In the pubertal group, the MAD was 1.26 ± 0.90 years with the GP method and 0.61 ± 0.47 years with the Sauvegrain method in boys (P < .001), while in girls, the MAD was 0.84 ± 0.60 years and 0.53 ± 0.36 years with the same 2 methods (P = .033). The chronological age for confirming puberty onset using the elbow was 12.2 years in boys and 10.3 years in girls.The bone ages of hand and elbow were different at puberty, and the elbow was a more reliable location for bone-age assessment at puberty. Puberty onset according to elbow occurred slightly earlier than expected.     

Effects of the Type of Intraoperative Fluid in Living Donor Kidney Transplantation: A Single-Center Retrospective Cohort Study

PurposePerioperative fluid management in kidney transplant recipients is crucial to supporting the fluid, acid-base, and electrolyte balance required for graft perfusion. However, the choice of intraoperative crystalloids in kidney transplantation remains controversial. We conducted a single-center retrospective cohort study to evaluate the impact of intraoperative fluids on acid-base and electrolyte balance and graft outcomes.Materials and MethodsWe included 282 living donor kidney transplant recipients from January 2010 to December 2017. Patients were classified into two groups based on the type of intraoperative crystalloids used (157 patients in the half saline group and 125 patients in the balanced crystalloid solutions group, Plasma-lyte).ResultsCompared with the half saline group, the Plasma-lyte group showed less metabolic acidosis and hyponatremia during surgery. Hyperkalemia incidence was not significantly different between the two groups. Changes in postoperative graft function assessed by blood urea nitrogen and creatinine were significantly different between the two groups. Patients in the Plasma-lyte group exhibited consistently higher glomerular filtration rates than those in the half saline group at 1 month and 1 year after transplantation after adjusting for demographic differences.ConclusionIntraoperative Plasma-lyte can lead to more favorable results in terms of acid-base balance during kidney transplantation. Patients who received Plasma-lyte showed superior postoperative graft function at 1 month and 1 year after transplantation. Further studies are needed to evaluate the superiority of intraoperative Plasma-lyte over other types of crystalloids in relation to graft outcomes.     

MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40

PurposeCerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species (ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40) in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion (I/R) injury.Materials and MethodsA mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemia in vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation (OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. The relationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays.ResultsBhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40 overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p was verified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reverse the effects of miR-494-3p overexpression on ROS production and cell apoptosis.ConclusionMiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.     

Therapeutic Efficacy of Spironolactone for Central Serous Chorioretinopathy

PurposeTo evaluate the therapeutic effects and safety of oral spironolactone (SPRL) in patients with central serous chorioretinopathy (CSC).Materials and MethodsThe medical records and imaging data of patients diagnosed with CSC and treated with SPRL were retrospectively reviewed. Central macular thickness (CMT), subretinal fluid (SRF) height, subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) at baseline, at 1, 3, and 6 months, and at the last visit after the treatment were analyzed.ResultsIn total, 103 patients with 107 eyes were included. The mean age of the patients was 51.5±9.3 years, and 77 (72.0%) were male. The mean follow-up duration was 48.6±40.2 weeks. The mean duration of oral SPRL therapy was 15.5±13.4 weeks. CMT, SRF height, and SFCT improved significantly at 1, 3, and 6 months after SPRL therapy and at the last follow-up. BCVA, however, showed no significant change at any time point. The rate of complete resolution of SRF at 1 month was higher in those with chronic CSC than in those with acute CSC (21.1% vs. 6.0%, respectively). Recurrence occurred in 14 (13.1%) eyes after the complete resolution of SRF. Older age (p=0.001), a greater number of previous intravitreal bevacizumab injections (p=0.006), and poor initial visual acuity (p=0.048) were associated with recurrence. No permanent adverse effects were observed.ConclusionOral SPRL showed therapeutic benefits in patients with CSC in terms of SRF resolution, but relatively frequent recurrence was observed, especially in older patients.     

A New General Fatigue Limit Diagram and Its Application of Predicting Die Fatigue Life during Cold Forging

Traditional fatigue fracture theory and practice focus principally on structural design. It is thus too conservative and inappropriate when used to predict the high-cycle fatigue life of dies used for metal forming, especially cold forging. We propose a novel mean stress correction model and diagram to predict the high-cycle fatigue lives of cold forging dies, which focuses on the upper part of the equivalent fatigue strength curve. Considering the features of die materials characterized by high yield strength and low ductility, a straight line is assumed for the tensile yield line. To the contrary, a general curve is used to represent the fatigue strength. They are interpolated, based on the distance ratio, when finding an appropriate equivalent fatigue strength curve at the mean stress and stress amplitude between the line and curve. The approach is applied to a well-defined literature example to verify its validity and shed light on the characteristics of die fatigue life. The approach is also applied to practical forging and useful qualitative results are obtained.     

Understanding Physicians’ and Nurses’ Adaption of National-Leading Patient Safety Culture Policy: A Qualitative Study in Tertiary and General Hospitals in Korea

BackgroundIn Korea, the safety culture is led by national policy. How the policy ensures a patient safety culture needs to be investigated. This study aimed to examine the way in which physicians and nurses regard, understand, or interpret the patient safety-related policy in the hospital setting.MethodsIn this qualitative study, we conducted four focus group interviews (FGIs) with 25 physicians and nurses from tertiary and general hospitals in South Korea. FGIs data were analyzed using thematic analysis, which was conducted in an inductive and interpretative way.ResultsThree themes were identified. The healthcare providers recognized its benefits in the forms of knowledge, information and training at least although the policy implemented by the law forcibly and temporarily. The second theme was about the interaction of the policy and the Korean context of healthcare, which makes a “turning point” in the safety culture. The final theme was about some strains and conflicts resulting from patient safety policy.ConclusionTo provide a patient safety culture, it is necessary to develop a plan to improve the voluntary participation of healthcare professionals and their commitment to safety. Hospitals should provide more resources and support for healthcare professionals.