Annexin A1 mimetic peptide Ac2-26 alleviates renal inflammatory injury in a diabetic mice model through the suppression of p38MAPK/NF-κB

Purpose: To examine the protective effect of mimetic peptide Ac2-26 of Annexin A1 (ANXA1) against renal inflammatory injury in a diabetic mice model. Methods: Twenty-four mice were randomized into three groups with eight mice per group. These included control group (CG), model group (MG) given intraperitoneal injection of streptozotocin (60 mg/kg), and AC2-26 group (AG) given AC2-26, 72 h after the induction of diabetes. Fasting blood glucose (FBG), blood lipids, and renal function in the mice were determined by Sysmex-180 Biochemistry Analyzer, while serum inflammatory factors in renal tissue were also determined. Results: Compared with the model group, there was a significant decrease in the levels of FBG, triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), oxidized LDL (ox-LDL), as well as in 24 h urinary protein, creatinine (Cr) and blood urea nitrogen (BUN), but a significant increase in body weight in AC2-26 group (p < 0.001). There was a significant decrease in TNF-α, IL-6, IL-1β, and IL-18 levels, as well as in mRNA levels and protein expressions of p38MAPK, NF-κBP6, ANXA1 in AC2-26 group when compared with the model group (p < 0.001). Conclusion: Annexin A1 is the target gene of p38MAPK. Annexin A1 mimetic peptide Ac2-26 alleviates renal inflammation by suppressing p38MAPK/NF-κB pathway, thus improving renal function in the diabetic mice model. Hence, the findings of this study provide a potential avenue for the development of an effective treatment for renal disease in diabetics

Annexin A1 mimetic peptide Ac2 26 alleviates renal inflammatory injury in diabetic mouse model by suppressing p38MAPK/NF κB

Purpose: To investigate the protective role of mimetic peptide Ac2-26 of annexin A1 (ANXA1) in regulating p38MAPK/NF-κB for renal inflammatory injury in a diabetic mouse model. Methods: The mice were divided into three groups (control, model and Ac2-26; n = 8). Control was untreated, normal mice, while Ac2-26 was treated with mimetic peptide Ac2-26 after induction of type I diabetes with streptozotocin (60 mg/kg). The model group was not further treated after induction of diabetes. The fasting blood glucose (FBG), blood lipid, and renal function were evaluated. Serum inflammatory factors in renal tissue were also assessed. Results: Compared with the model group, there was a significant decrease in the levels of FBG, blood lipids (TG, TC, LDL and ox-LDL), KI, 24 h urinary protein, Cr and BUN, and significant increase in body weight in AC2-26 group (p < 0.001). There was a marked decrease in TNF-α, IL-6, IL-1β, and IL-18 levels, as well as levels of mRNA and protein expressions of p38MAPK, NF-κBP6 and ANXA1 in AC2-26 group when compared with the model group (p < 0.001). Conclusion: ANXA1 is the target gene of p38MAPK, and mimetic peptide Ac2-26 alleviates renal inflammation by suppressing p38MAPK/NF-κB pathway, thus improving renal function in diabetic mice models. This finding suggests a probable approach to developing an effective treatment for renal inflammation in diabetic renal injury

Association of serum lycopene concentrations with all-cause and cardiovascular mortality among individuals with chronic kidney disease: A cohort study

BackgroundLycopene is one of the hydrocarbon carotenoids which is largely studied for its strong antioxidant and anti-inflammatory properties, as well as improvement of endothelial function and anti-arteriosclerosis effects. The use of lycopene has been shown to reduce mortality in the general population. However, few studies have examined the association between serum lycopene level and all-cause and cardiovascular mortality among participants with chronic kidney disease (CKD).MethodThis study included 7,683 adults with CKD from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and NHANES 2001–2006. Mortality status and cause of death were ascertained by linkage to National Death Index records through 31 December 2018. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% CIs for mortality from all-cause and cardiovascular disease (CVD).ResultDuring a median follow-up time of 309 months, there were 5,226 total deaths. The median (interquartile range) serum lycopene concentration was 20.0 (12.0, 32.0) μg/dl. After fully adjusted, restricted cubic spline analyses reported that higher serum lycopene concentrations were significantly associated with decreased risk of all-cause and CVD mortality in participants with CKD (P < 0.001, P = 0.001). When extreme quartiles of serum lycopene concentrations were compared, the multivariable-adjusted HR (95% CI) was 0.778 (0.714–0.848) for all-cause mortality (P < 0.001), and 0.791 (0.692–0.905) for CVD mortality (P < 0.001). Specifically, higher serum lycopene decreased the risk of all-cause and CVD mortality at both CKD stage 1–2 and stage 3–5. Further subgroup analyses and sensitivity analyses supported the current results.ConclusionHigher serum lycopene was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD. These findings suggested that maintain serum lycopene concentrations could lower mortality risk in CKD patients

Homer1a Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Stress After Ischemic Reperfusion Injury by Inhibiting the PERK Pathway

Homer1a is the short form of a scaffold protein that plays a protective role in many forms of stress. However, the role of Homer1a in cerebral ischemia/reperfusion (I/R) injury and its potential mechanism is still unknown. In this study, we found that Homer1a was upregulated by oxygen and glucose deprivation (OGD) and that overexpression of Homer1a alleviated OGD-induced lactate dehydrogenase (LDH) release and cell death in cultured cortical neurons. After OGD treatment, the overexpression of Homer1a preserved mitochondrial function, as evidenced by less cytochrome c release, less reactive oxygen species (ROS) production, less ATP and mitochondrial membrane potential (MMP) loss, less caspase-9 activation, and inhibition of endoplasmic reticulum (ER) stress confirmed by the decreased expression of phosphate-PKR-like ER Kinase (p-PERK)/PERK and phosphate- inositol-requiring enzyme 1 (p-IRE1)/IRE1 and immunofluorescence (IF) staining. In addition, mitochondrial protection of Homer1a was blocked by the ER stress activator Tunicamycin (TM) with a re-escalated ROS level, increasing ATP and MMP loss. Furthermore, Homer1a overexpression-induced mitochondrial stress attenuation was significantly reversed by activating the PERK pathway with TM and p-IRE1 inhibitor 3,5-dibromosalicylaldehyde (DBSA), as evidenced by increased cytochrome c release, increased ATP loss and a higher ROS level. However, activating the IRE1 pathway with TM and p-PERK inhibitor GSK2656157 showed little change in cytochrome c release and exhibited a moderate upgrade of ATP loss and ROS production in neurons. In summary, these findings demonstrated that Homer1a protects against OGD-induced injury by preserving mitochondrial function through inhibiting the PERK pathway. Our finding may reveal a promising target of protecting neurons from cerebral I/R injury

Gender differences in behavioral regulation in four societies: The United States, Taiwan, South Korea, and China

The current study investigates gender differences in behavioral regulation in four societies: the United States, Taiwan, South Korea, and China. Directly assessed individual behavioral regulation (Head–Toes–Knees–Shoulders, HTKS), teacher-rated classroom behavioral regulation (Child Behavior Rating Scale, CBRS) and a battery of school readiness assessments (mathematics, vocabulary, and early literacy) were used with 814 young children (ages 3–6 years). Results showed that girls in the United States had significantly higher individual behavioral regulation than boys, but there were no significant gender differences in any Asian societies. In contrast, teachers in Taiwan, South Korea, as well as the United States rated girls as significantly higher than boys on classroom behavioral regulation. In addition, for both genders, individual and classroom behavioral regulation were related to many aspects of school readiness in all societies for girls and boys. Universal and culturally specific findings and their implications are discussed

Arab Spring and Occupy

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library

Arab Spring and Occupy

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library

Always Judging

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library

Lysozyme-Triggered Nanodiamond Contact Lens for Glaucoma Treatment & Phenotypically-based Combinatorial Drug Optimization for Multiple Myeloma Treatment

In glaucoma treatment, ocular devices such as drug-loaded contact lenses have recentlyemerged as preferred candidates over eyedrops. Timolol maleate (TM), a prevalent glaucoma drug, exhibits side effects when excess drug enters the systemic circulation. Unlike eyedrops and drug-soaked lenses, new designs should provide sustained release and minimize undesirable burst release. Current innovations have not addressed the important issue of drug elution from contact lens during wet storage and shipment. Here we present a nanodiamond (ND)-embedded contact lens capable of lysozyme-triggered release of TM for sustained therapy. We found that ND-nanogel containing lysozyme-cleavable polymers enabled the controlled and sustained release of TM in the presence of lysozyme. Nanodiamonds also improved the mechanical properties of the poly-HEMA lenses without compromising on water content, oxygenpermeability and optical clarity. In vitro cell viability assays on primary trabecular meshwork cells revealed that the released TM retained their antioxidant activity – an indicator of timolol efficacy. This successful lysozyme activation of our functionalized ND nanogel can be easily applied to other diseases and drugs where localized triggered release is desired.Conventional combinatorial treatment for multiple myeloma and other cancers uses an additive approach of maximum tolerated doses from single-drug experiments. These doses do not reflect true drug behavior in combinatorial therapy. A rapid and robust platform is necessary to optimize multiple parameters to find the best drug combination for improved efficacy and safety. Here, we present Response Surface Optimization (RSO) where we rapidly narrowed down our top three myeloma drug candidates (Bortezomib-Panobinostat-Dexamethasone) from a starting list of fourteen drugs in a short span of five months. The mechanism-independent RSO platform screens drugs based on maximizing the therapeutic window – increased healthy cell viability and decreased cancer cell viability. After the 1st iteration experiment, a linear regressionexperimental process (equation) is generated using MATLAB to reconcile the empirical data. Undesirable candidates are removed before performing a 2nd screening iteration. In the 3rd iteration, the optimum drug concentrations of the best drug combinations are determined. Response surface maps for output based on multi-parameters are plotted and the optimum is determined. Interestingly, this three-drug combination was the focus of recent myeloma clinical trials for refractory and relapsed patients. While conventional drug screening approaches demand huge time and money investment, the RSO platform rapidly and accurately converges on prime solutions. The RSO is applicable to the clinic where inter-patient variability requires adaptive treatment interventions based on individual clinical outcomes