Dopamine-conjugated extracellular vesicles induce autophagy in Parkinson's disease.

The application of extracellular vesicles (EVs) as vehicles for anti-Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood-brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose-derived stem cell EVs (Dopa-EVs) utilizing a facile, two-step cross-linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies.

A Complex of Matisum. and L. Improves Menopausal Symptoms and Supports Healthy Aging in Women.

We evaluated the efficacy and safety of MS-10 for the treatment of menopausal symptoms. A double-blind randomized placebo-controlled clinical trial was performed in 71 premenopausal women for 4 and 12 weeks. A total of 12 individual menopausal symptom scores were assessed using the Kupperman index.

Structural mechanism for regulation of Rab7 by site-specific monoubiquitination.

Site-specific ubiquitination can regulate the functions of Rab proteins in membrane trafficking. Previously we showed that site-specific monoubiquitination on Rab5 downregulates its function. Rab7 acts in the downstream of Rab5.

Study of the process-induced cell damage in forced extrusion bioprinting.

With remarkable developments in technologies, the possibility of replacing injured tissue or organs with artificial ones via three-dimensional bioprinting is being improved. The basic prerequisite for successful application of bioprinting is high cell survival following printing. In this study, numerical calculations and experiments were performed to understand cell damage process incurred by forced extrusion bioprinters.

Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases.

Extracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action.

ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones.

AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae.

Ectopic Expression of OsPYL/RCAR7, an ABA Receptor Having Low Signaling Activity, Improves Drought Tolerance without Growth Defects in Rice.

Overexpression of abscisic acid (ABA) receptors has been reported to enhance drought tolerance, but also to cause stunted growth and decreased crop yield. Here, we constructed transgenic rice for all monomeric ABA receptors and observed that only transgenic rice over-expressing showed similar phenotype with wild type, without total yield loss when grown under normal growth condition in a paddy field. Even though transgenic rice over-expressing / showed neither an ABA-sensitivity nor an osmotic stress tolerance in plate assay, it showed drought tolerance.

Selection and functional identification of a synthetic partial ABA agonist, S7.

The stress hormone abscisic acid (ABA) helps plants to survive under abiotic stresses; however, its use as an agrochemical is limited by its chemical instability and expense. Here, we report the development of an in vivo screening system to isolate chemicals able to induce ABA signalling responses in rice (Oryza sativa) protoplasts. This system consists of an ABA-hypersensitive synthetic promoter containing ABRE and DRE motifs driving a luciferase reporter gene.

The effect of visceral fat on the hemodilution effect of serum carcinoembryonic antigen in Korean population.

Objective: To investigate the relationship between visceral fat and the hemodilution effect of carcinoembryonic antigen in both sexes.

Methods: A total of 15,340 females and 20,024 males who visited the health promotion center at Chung-Ang University Hospital from 2011 to 2014 were retrospectively collected. Correlation analysis and chi-square test for linear by linear association were used to determine the correlation between carcinoembryonic antigen concentration, carcinoembryonic antigen mass and visceral fat.

Comprehensive survey of the VxGΦL motif of PP2Cs from Oryza sativa reveals the critical role of the fourth position in regulation of ABA responsiveness.

Regulation of abscisic acid (ABA) signaling is crucial in balancing responses to abiotic stresses and retaining growth in planta. An ABA receptor (PYL/RCAR) and a protein phosphatase (PP2C), a co-receptor, form a complex upon binding to ABA. Previously we reported that the second and fourth positions in the VxGΦL motif of PP2Cs from Oryza sativa are critical in the interaction of PP2Cs with PYL/RCARs.

Two Clade A Phosphatase 2Cs Expressed in Guard Cells Physically Interact With Abscisic Acid Signaling Components to Induce Stomatal Closure in Rice.

Background: The core ABA signaling components functioning in stomatal closure/opening, namely ABA receptors, phosphatases, SnRK2s and SLAC1, are well characterized in Arabidopsis, but their functions in guard cells of rice have not been extensively studied.

Results: In this study, we confirmed that OsSLAC1, the rice homolog of AtSLAC1, is specifically expressed in rice guard cells. Among the rice SAPKs, SAPK10 was specifically expressed in guard cells.

Structural determinants for pyrabactin recognition in ABA receptors in Oryza sativa.

We determined the structure of OsPYL/RCAR3:OsPP2C50 complex with pyrabactin. Our results suggest that a less-conserved phenylalanine of OsPYL/RCAR subfamily I is one of considerations of ABA agonist development for Oryza sativa. Pyrabactin is a synthetic chemical mimicking abscisic acid (ABA), a naturally occurring phytohormone orchestrating abiotic stress responses.

Modulation of ABA Signaling by Altering VxGΦL Motif of PP2Cs in Oryza sativa.

The abscisic acid (ABA) signaling pathway is regulated by clade A type 2C protein phosphatases (PP2CAs) in plants. In the presence of ABA, PP2Cs release stress/ABA-activated protein kinases by binding to ABA-bound receptors (PYL/RCARs) for activation. Although the wedging tryptophan in PP2Cs is critical in the interaction with PYL/RCARs in Arabidopsis and rice, it remains elusive as to how other interface regions are involved in the interaction.

New conformations of linear polyubiquitin chains from crystallographic and solution-scattering studies expand the conformational space of polyubiquitin.

The conformational flexibility of linkage-specific polyubiquitin chains enables ubiquitylated proteins and their receptors to be involved in a variety of cellular processes. Linear or Met1-linked polyubiquitin chains, associated with nondegradational cellular signalling pathways, have been known to adopt multiple conformations from compact to extended conformations. However, the extent of such conformational flexibility remains open.

Primary cervical choriocarcinoma during viable intrauterine pregnancy.

A 31-year-old multigravida woman at 27 weeks' gestation was admitted with vaginal bleeding and a hypervascular mass near the cervix on ultrasonography. After discharge with improvement, she was readmitted the next day for uncontrolled, heavy vaginal bleeding and underwent emergency cesarean section at 29 weeks' gestation. A 3-cm friable mass found near the cervix was removed surgically; this lesion was shown to be primary cervical choriocarcinoma.

Molecular determinants of polyubiquitin recognition by continuous ubiquitin-binding domains of Rad18.

Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins through its bipartite ubiquitin-binding domains UBZ and LRM with extra residues between them. Rad18 binds K63-linked polyubiquitin chains as well as K48-linked ones and monoubiquitin. However, the detailed molecular basis of polyubiquitin recognition by UBZ and LRM remains unclear.

Molecular determinants of the interaction between Doa1 and Hse1 involved in endosomal sorting.

Yeast Doa1/Ufd3 is an adaptor protein for Cdc48 (p97 in mammal), an AAA type ATPase associated with endoplasmic reticulum-associated protein degradation pathway and endosomal sorting into multivesicular bodies. Doa1 functions in the endosomal sorting by its association with Hse1, a component of endosomal sorting complex required for transport (ESCRT) system. The association of Doa1 with Hse1 was previously reported to be mediated between PFU domain of Doa1 and SH3 of Hse1.

Structure-based elucidation of the regulatory mechanism for aminopeptidase activity.

The specificity of proteases for the residues in and length of substrates is key to understanding their regulatory mechanism, but little is known about length selectivity. Crystal structure analyses of the bacterial aminopeptidase PepS, combined with functional and single-molecule FRET assays, have elucidated a molecular basis for length selectivity. PepS exists in open and closed conformations.

ERCC1 C19007T polymorphism and the risk and invasiveness of cervical cancer in Korean women.

Aim: Various DNA alterations by environmental or endogenous carcinogens, if not repaired, can cause genetic mutagenesis, resulting in carcinogenesis. A polymorphic variant of excision repair cross-complementation group 1 (ERCC1) (the DNA repair gene) may be associated with carcinogenesis due to reduced DNA repair capacity. The aim of this study was to investigate whether the ERCC1 C19007T polymorphism might be associated with the increased risk and invasiveness of cervical cancer in Korean women.

Phase II Study of Consolidation Chemotherapy after Adjuvant or Primary Concurrent Chemoradiation Using Paclitaxel and Carboplatin to Treat High-Risk Early-Stage or Locally Advanced Cervical Cancer.

Purpose: This study investigated the efficacy and toxicity associated with consolidation chemotherapy using paclitaxel and carboplatin after concurrent chemoradiation (CCR) in cervical cancer patients.

Materials And Methods: From a total of 37 patients, 19 with International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA cervical cancer (group 1) underwent surgery followed by consolidation chemotherapy after CCR, and 18 with stage IIB-IVA disease (group 2) received consolidation chemotherapy after primary CCR. Three cycles of chemotherapy using paclitaxel (135 mg/m(2)) and carboplatin (AUC 5.

Underuse of ovarian transposition in reproductive-aged cancer patients treated by primary or adjuvant pelvic irradiation.

Aim: To investigate the application status of ovarian transposition (OT) in reproductive-aged cancer patients undergoing radiation therapy.

Material & Methods: Between November 1999 and December 2008, 2524 patients had received pelvic irradiation at Seoul National University Hospital. We filtered the patients with the indications of (i) within 12 to 40 years of age, and (ii) receiving primary or adjuvant pelvic irradiation.

Evaluation of preoperative criteria used to predict lymph node metastasis in endometrial cancer.

Objective: To evaluate whether we could accurately predict lymph node (LN) metastasis with preoperative tests in endometrial cancer. Design. Retrospective study.