Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice.

BACKGROUND: Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer from peripheral neuropathy. Nerve fiber loss in DN occurs due to myelin defects and is characterized by symptoms of impaired nerve function. Schwann cells (SCs) are the main support cells of the peripheral nervous system and play important roles in several pathways contributing to the pathogenesis and development of DN. We previously reported that human tonsil-derived mesenchymal stem cells differentiated into SCs (TMSC-SCs), named neuronal regeneration-promoting cells (NRPCs), which cells promoted nerve regeneration in animal models with peripheral nerve injury or hereditary peripheral neuropathy. METHODS: In this study, NRPCs were injected into the thigh muscles of BKS-db/db mice, a commonly used type 2 diabetes model, and monitored for 26 weeks. Von Frey test, sensory nerve conduction study, and staining of sural nerve, hind foot pad, dorsal root ganglia (DRG) were performed after NRPCs treatment. RESULTS: Von Frey test results showed that the NRPC treatment group (NRPC group) showed faster responses to less force than the vehicle group. Additionally, remyelination of sural nerve fibers also increased in the NRPC group. After NRPCs treatment, an improvement in response to external stimuli and pain sensation was expected through increased expression of PGP9.5 in the sole and TRPV1 in the DRG. CONCLUSION: The NRPCs treatment may alleviate DN through the remyelination and the recovery of sensory neurons, could provide a better life for patients suffering from complications of this disease.

Polymeric Binder Design for Sustainable Lithium-Ion Battery Chemistry.

The design of binders plays a pivotal role in achieving enduring high power in lithium-ion batteries (LIBs) and extending their overall lifespan. This review underscores the indispensable characteristics that a binder must possess when utilized in LIBs, considering factors such as electrochemical, thermal, and dispersion stability, compatibility with electrolytes, solubility in solvents, mechanical properties, and conductivity. In the case of anode materials, binders with robust mechanical properties and elasticity are imperative to uphold electrode integrity, particularly in materials subjected to substantial volume changes. For cathode materials, the selection of a binder hinges on the crystal structure of the cathode material. Other vital considerations in binder design encompass cost effectiveness, adhesion, processability, and environmental friendliness. Incorporating low-cost, eco-friendly, and biodegradable polymers can significantly contribute to sustainable battery development. This review serves as an invaluable resource for comprehending the prerequisites of binder design in high-performance LIBs and offers insights into binder selection for diverse electrode materials. The findings and principles articulated in this review can be extrapolated to other advanced battery systems, charting a course for developing next-generation batteries characterized by enhanced performance and sustainability.

Regularity of cervical cancer screening in Korea: analysis using national public data for 12 years.

OBJECTIVE: To assess the frequency of regular uptake of national cervical cancer screening (CCS) program and identify associated factors among Korean women. METHODS: This study is a fundamental investigation that employs openly accessible public data of Korea through secondary data analysis. A cohort of 4,663 women from the 2007-2012 Korean National Health and Nutrition Examination Survey, was followed up for up to 12 years (2007-2018) to obtain the frequency of national CCS. Compliance level with CCS was categorized, and an ordinal logistic regression model was employed to investigate the contributing factors. RESULTS: The regular uptake of CCS in South Korea was low at 18.9%. The trend of regular screening showed significant association with various factors, including age (40-59 years), household income (100%-150% bracket), occupation (service workers), place of residence (small to medium sized cities), education level (middle school graduates), marital status (married), and possession of private insurance. Moreover, individuals with a history of non-cervical cancer or carcinoma in situ of the cervix, a family history of cervical cancer, or a higher frequency of general check-ups demonstrated a stronger adherence to regular CCS uptake. CONCLUSION: Our findings revealed that regular participation in CCS in Korea was lower than anticipated, with factors such as socioeconomic status, personal history of gynecologic issue, and frequency of general health check-ups playing influential roles. However, further research, including an exploration of unexamined psychological barriers to screening, is necessary to gain a better understanding the reasons behind the reduced rates of regular CCS among Korean women.

Synthesis and biological evaluation of (phenylpiperazinyl-propyl)arylsulfonamides as selective 5-HT(2A) receptor antagonists.

A novel series of 5-HT(2A) ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)butan-2-yl)-arylsulfonamide compounds were obtained. The binding of these compounds to the 5-HT(2A), 5-HT(2C), and 5-HT(7) receptors was evaluated. Most of the compounds showed IC(50) values of less than 100 nM and exhibited high selectivity for the 5-HT(2A) receptor. Among the synthesized compounds, 16a and 16d showed good affinity at 5-HT(2A) (IC(50)=0.7 nM and 0.5 nM) and good selectivity over 5-HT(2C) (50-100 times) and 5-HT(7) (1500-3000 times).

Preparation of piperazine derivatives as 5-HT7 receptor antagonists.

Twenty-four compounds of 4-methoxy-N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] benzene sulfonamides and N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] naphthyl sulfonamides were prepared and evaluated as 5-HT(7) receptor antagonists. Most of the compounds showed the IC(50) values of 12-580nM. Four methyl branched analogues were also obtained, but the activity for methyl branched analogues was almost same as its straight chain congeners. Among the synthesized compounds, 3c showed a good activity on 5-HT(7) receptors and a good selectivity on 5-HT(1a), 5-HT(2a), 5-HT(2c), and 5-HT(6) receptors.

Okadaic acid induces JNK activation, bim overexpression and mitochondrial dysfunction in cultured rat cortical neurons.

Apoptosis via tau phosphorylation has been implicated in the selective neuronal losses seen in Alzheimer's disease (AD). Previous studies in vivo and in cultured neurons have shown that okadaic acid (OA) evokes tau phosphorylation to initiate a neurodegeneration that resembles the pathogenesis of AD. In an effort to identify additional key molecules in this neurodegeneration, we treated cultured rat neurons with OA and examined the apoptosis-related effects, such as changes in mitochondrial activity and expression levels of JNK, Bim, Bad, Bax and caspase-3. Western blotting revealed that phosphorylation of JNK and c-jun occurred first, followed by increased expression of Bim and subsequent caspase-3 activation in OA-treated neurons. In contrast, Bad levels decreased as early as 4 h after OA treatment. Immunocytochemistry showed that the increased phospho-JNK immunoreactivity was localized in the cytosol of degenerating neurons, while increased phospho-c-jun was localized in the nucleus. The mitochondria showed decreased membrane potential and increased swelling after OA treatment. Collectively, these data suggest that JNK- and Bim-related mitochondrial dysfunction is involved in OA-induced neurodegeneration.