Silver(I) Complexes with Mefenamic Acid and Nitrogen Heterocyclic Ligands: Synthesis, Characterization, and Biological Evaluation.

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.

Impact of Gender-Role Attitudes and Mental Health on Hostile Sexism and Acceptance of Cosmetic Surgery.

BACKGROUND: Each year, tens of thousands of people worldwide choose to undergo cosmetic surgery in order to alter their appearance. In recent years, young people have gradually emerged to comprise the main driving force behind the increasing demand for cosmetic surgery. Previous studies have found that sexism may motivate young people to undergo such surgeries. However, few studies have been conducted to determine if this psychological mechanism influences the acceptance of cosmetic surgery among Chinese university students. METHODS: A total of 579 Chinese university students (280 girls and 299 boys, 17-20 years) volunteered to participate in the online survey. They completed a questionnaire containing the Ambivalent Sexism Inventory, the 12-item General Health Questionnaire, the Gender-Role Attitudes Questionnaire and the Acceptance of Cosmetic Surgery Scale. We firstly evaluated the underlying factor structure of the Acceptance of Cosmetic Surgery Scale using exploratory and confirmatory factor analyses, and exploring pattern of associations between the constructs was analyzed via path analysis. RESULTS: According to the findings, hostile sexism was associated with greater levels of acceptance toward cosmetic surgery. Moreover, gender-role attitudes mediated the link between hostile sexism and the acceptance of cosmetic surgery, and this mediation was positively influenced by general mental health. CONCLUSION: Our study contributes to a deeper understanding of Chinese university students' attitudes toward cosmetic surgery, hostile sexism may contribute to normalizing traditional gender stereotypes and encourage cosmetic surgery acceptability among Chinese university students. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Investigation on the Corrosion Resistance Properties of Cobalt-Chromium-Molybdenum Alloy Artificial Human Body Components with Robust Biomimetic Superhydrophobic and Slippery Surfaces Based on Laser Texturing.

Cobalt-chromium-molybdenum alloy is used as a material for artificial human body components such as artificial hip joint and artificial denture and is often affected by electrochemical corrosion in human body fluids and saliva, which leads to inflammatory reactions and damage to the surrounding tissues as well as loosening and failure of the body components themselves. Few studies have been conducted to prepare corrosion-resistant coatings on the surface of Co28Cr6Mo. In this study, we used laser texturing to process a bionic 3D micronanocomposite structure on the surface of Co28Cr6Mo and quickly prepared a superhydrophobic and slippery surface coating with excellent corrosion resistance using polydimethylsiloxane solution and silicone oil modification. This surface had ultralow surface adhesion and good robustness of durability and abrasion resistance, reducing bacterial colonization or tissue adhesion and solving the problem of the lack of stability of the superhydrophobic surface. Microgrid grooves and layered nanoparticles were structurally responsible for the variation in wettability. The formation mechanism and composition of the prepared coatings were further analyzed. Electrochemical corrosion experiments were conducted on the surface in simulating body fluid and saliva environments, which showed the enhanced corrosion resistance of the prepared surface in the human body. These findings can further develop the surface functional modification of Co28Cr6Mo, accelerating basic and applied research studies on artificial human components.

[A glass micropipette vacuum technique of cerebrospinal fluid sampling in C57BL/6 mice].

The purpose of this study was to establish a suitable method for extracting cerebrospinal fluid (CSF) from C57BL/6 mice. A patch clamp electrode puller was used to draw a glass micropipette, and a brain stereotaxic device was used to fix the mouse's head at an angle of 135° from the body. Under a stereoscopic microscope, the skin and muscle tissue on the back of the mouse's head were separated, and the dura mater at the cerebellomedullary cistern was exposed. The glass micropipette (with an angle of 20° to 30° from the dura mater) was used to puncture at a point 1 mm inboard of Y-shaped dorsal vertebral artery for CSF sampling. After the first extraction, the glass micropipette was connected with a 1 mL sterile syringe to form a negative pressure device for the second extraction. The results showed that the successful rate of CSF extraction was 83.33% (30/36). Average CSF extraction amount was (7.16 ± 0.43) µL per mouse. In addition, C57BL/6 mice were given intranasally ferric ammonium citrate (FAC) to establish a model of brain iron accumulation, and the CSF extraction technique established in the present study was used for sampling. The results showed that iron content in the CSF from the normal saline control group was not detected, while the iron content in the CSF from FAC-treated group was (76.24 ± 38.53) µmol/L, and the difference was significant. These results suggest that glass micropipette vacuum technique of CSF sampling established in the present study has the advantages of simplicity, high success rate, large extraction volume, and low bleeding rate, and is suitable for the research on C57BL/6 mouse neurological disease models.

Alterations in neural oscillations related to working memory deficit in temporal lobe epilepsy.

OBJECTIVE: Working memory (WM) is critical for higher level cognition, but the underlying neural mechanisms are not fully understood. Impaired WM affects routine daily activities and is observed in patients with temporal lobe epilepsy (TLE). This study investigated neural oscillations associated with different WM phases, to determine the specific neural activity linked with the phases of WM impairment. METHODS: Patients with TLE (n = 52) and healthy volunteers (n = 35) completed a WM task, during which 34-channel electroencephalogram signals were recorded. Characteristic neural oscillation patterns during each WM phase were compared between the 2 groups. RESULTS: Patients with TLE showed decreased theta power during the encoding phase of WM, which was associated with reduced accuracy in the WM task. Altered theta power in the frontal region of the brain during the encoding phase was associated with a longer reaction time. CONCLUSIONS: Alterations in theta oscillation are related to WM impairment in patients with TLE and may serve as an early marker for evaluating WM deficits. SIGNIFICANCE: This study provides an early marker for evaluating WM deficits in TLE.

[Exosomes and their roles in neurodegenerative diseases: from pathogenic, diagnostic and therapeutical perspectives].

Exosomes are extracellular membranous vesicles with a diameter of 30-100 nm derived from a variety of eukaryocytes. The cargo of exosomes includes proteins, lipids, nucleic acids, and substances of the cells from which they originate. They can transfer functional cargo to neighboring and distal cells, therefore contributing to intercellular communication in both physiological and pathological processes. In recent years, it was shown that exosomes in several neurodegenerative diseases are closely related to the transmission of disease-related misfolded proteins (such as α-synuclein, tau, amyloid ß-protein, etc). These proteins are transported by exosomes, thus promoting the propagation to unaffected cells or areas and accelerating the progression of neurodegenerative diseases. This review focuses on the origin and composition, biological synthesis, secretion, function of exosomes, as well as their roles in the pathogenesis and progression of neurodegenerative diseases. In addition, we also discuss that exosomes can serve as biomarkers and drug delivery vehicles, and play a role in the diagnosis and treatment of neurodegenerative diseases.

AHSA1 is a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma.

BACKGROUND: Currently, multiple myeloma (MM) is still an incurable plasma cell malignancy in urgent need of novel therapeutic targets and drugs. METHODS: Bufalin was known as a highly toxic but effective anti-cancer compound. We used Bufalin as a probe to screen its potential targets by proteome microarray, in which AHSA1 was the unique target of Bufalin. The effects of AHSA1 on cellular proliferation and drug resistance were determined by MTT, western blot, flow cytometry, immunohistochemistry staining and xenograft model in vivo. The potential mechanisms of Bufalin and KU-177 in AHSA1/HSP90 were verified by co-immunoprecipitation, mass spectrometry, site mutation and microscale thermophoresis assay. RESULTS: AHSA1 expression was increased in MM samples compared to normal controls, which was significantly associated with MM relapse and poor outcomes. Furthermore, AHSA1 promoted MM cell proliferation and proteasome inhibitor (PI) resistance in vitro and in vivo. Mechanism exploration indicated that AHSA1 acted as a co-chaperone of HSP90A to activate CDK6 and PSMD2, which were key regulators of MM proliferation and PI resistance respectively. Additionally, we identified AHSA1-K137 as the specific binding site of Bufalin on AHSA1, mutation of which decreased the interaction of AHSA1 with HSP90A and suppressed the function of AHSA1 on mediating CDK6 and PSMD2. Intriguingly, we discovered KU-177, an AHSA1 selective inhibitor, and found KU-177 targeting the same site as Bufalin. Bufalin and KU-177 treatments hampered the proliferation of flow MRD-positive cells in both primary MM and recurrent MM patient samples. Moreover, KU-177 abrogated the cellular proliferation and PI resistance induced by elevated AHSA1, and decreased the expression of CDK6 and PSMD2. CONCLUSIONS: We demonstrate that AHSA1 may serve as a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma.

Corrigendum: Alterations in Neural Networks During Working Memory Encoding Related to Cognitive Impairment in Temporal Lobe Epilepsy.

[This corrects the article DOI: 10.3389/fnhum.2021.770678.].

Synthesis, Characterization, and Evaluation of Nanoparticles Loading Adriamycin Based on 2-Hydroxypropyltrimethyl Ammonium Chloride Chitosan Grafting Folic Acid.

Chitosan nanoparticles have been considered as potential candidates for drug loading/release in drug delivery systems. In this paper, nanoparticles (HACAFNP) loading adriamycin based on 2-hydroxypropyltrimethyl ammonium chloride chitosan grafting folic acid (HACF) were synthesized. The surface morphology of the novel nanoparticles was spherical or oval, and the nanoparticles exhibited a relatively small hydrodynamic diameter (85.6 ± 2.04 nm) and positive zeta potential (+21.06 ± 0.96 mV). The drug release of nanoparticles was assayed and represented a burst effect followed by a long-term steady release. Afterward, the antioxidant efficiencies of nanoparticles were assayed. In particular, the target nanoparticles exhibited significant enhancement in radical scavenging activities. Cytotoxicities against cancer cells (MCF-7, BGC-823, and HEPG-2) were estimated in vitro, and results showed nanoparticles inhibited the growth of cancer cells. It's worth noting that the inhibition index of HACAFNP against BGC-823 cells was 71.19% with the sample concentration of 25 µg/mL, which was much higher than the inhibitory effect of ADM. It was demonstrated that the novel nanoparticles with dramatically enhanced biological activity, reduced cytotoxicity, and steady release could be used as the practical candidates for drug loading/release in a delivery system.

Alterations in Neural Networks During Working Memory Encoding Related to Cognitive Impairment in Temporal Lobe Epilepsy.

Objective: The aim of the current study was to investigate the alterations in the neural networks of patients with temporal lobe epilepsy (TLE) during working memory (WM) encoding. Methods: Patients with TLE (n = 52) and healthy volunteers (n = 35) completed a WM task, during which 34-channel electroencephalogram signals were recorded. The neural networks during WM encoding were calculated in TLE patients with (TLE-WM) and without (TLE-N) WM deficits. Results: Functional connectivity strength decreased, and the theta network was altered in the TLE-WM group, although no significant differences in clinical features were observed between the TLE-N and TLE-WM groups. Conclusions: Not all patients with TLE present with cognitive impairments and alterations in the theta network were identified in TLE patients with functional cognitive deficits. Significance: The theta network may represent a sensitive measure of cognitive impairment and could predict cognitive outcomes among patients with TLE.

Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths due to its highly aggressive biological nature and resistance to chemotherapy. Previous studies indicate that miR-21 is an important regulator in the activation of cancer-associated fibroblasts (CAFs). However, whether miR-21 in CAFs would regulate PDAC's tumor microenvironment and lead to drug resistance remain unknown. In this study, we evaluated the relationship between CAF activation, miR-21 expression, and drug resistance using tumor samples from PDAC patients. We changed the miR-21 expression level in CAFs and tested its roles in regulating the function of CAFs. In addition, we explored the roles of miR-21 in CAFs in the development of PDAC using an animal model. We found that PDAC patients who were resistant to gemcitabine treatment tended to have higher miR-21 expression and more activated CAFs. An in vitro study showed that CAFs with high miR-21 expression had elevated MMP-3, MMP-9, PDGF, and CCL-7 expression and promoted the invasion of PDAC cell lines. miR-21 overexpression also contributed to the activation of CAFs by regulating the PDCD4 gene. The in vivo study showed that upregulating miR-21 in CAFs promoted PDAC desmoplasia and increased its drug resistance to gemcitabine treatment, but downregulating miR-21 in CAFs suppressed desmoplasia and enhanced the effect of gemcitabine. We concluded that miR-21 promoted the activation of CAFs and contributed to the drug resistance of PDAC.

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer.

AIM: To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). METHODS: An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. RESULTS: The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI (P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites (P = 0.009), liver metastasis (P = 0.035), and decreased survival time (P = 0.022). N-syndecan expression was significantly associated with tumor size (P = 0.025), but not with survival time (P = 0.539). CONCLUSION: High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer.