PINK1 and Parkin rescue motor defects and mitochondria dysfunction induced by a patient-derived HSPB3 mutant in Drosophila models.

Small heat shock proteins (sHSPs) are ATP-independent molecular chaperones with the α-crystalline domain that is critical to their chaperone activity. Within the sHSP family, three (HSPB1, HSPB3, and HSPB8) proteins are linked with inherited peripheral neuropathies, including distal hereditary motor neuropathy (dHMN) and Charco-Marie-Tooth disease (CMT). In this study, we introduced the HSPB3 Y118H (HSPB3Y118H) mutant gene identified from the CMT2 family in Drosophila. With a missense mutation on its α-crystalline domain, this human HSPB3 mutant gene induced a loss of motor activity accompanied by reduced mitochondrial membrane potential in fly neuronal tissues. Moreover, mitophagy, a critical mechanism of mitochondrial quality control, is downregulated in fly motor neurons expressing HSPB3Y118H. Surprisingly, PINK1 and Parkin, the core regulators of mitophagy, successfully rescued these motor and mitochondrial abnormalities in HSPB3 mutant flies. Results from the first animal model of HSPB3 mutations suggest that mitochondrial dysfunction plays a critical role in HSPB3-associated human pathology.

Human HSPB1 mutation recapitulates features of distal hereditary motor neuropathy (dHMN) in Drosophila.

Distal hereditary motor neuropathies (dHMN) are a group of inherited peripheral nerve disorders characterized by length-dependent motor neuron weakness and subsequent muscle atrophy. Missense mutations in the gene encoding small heat shock protein HSPB1 (HSP27) have been associated with hereditary neuropathies including dHMN. HSPB1 is a member of the small heat shock protein (sHSP) family characterized by a highly conserved α-crystallin domain that is critical to their chaperone activity. In this study, we modeled HSPB1 mutant-induced neuropathies in Drosophila using a human HSPB1S135F mutant that has a missense mutation in its α-crystallin domain. Overexpression of the HSPB1 mutant produced no significant defect in the Drosophila development, however, a partial reduction in the life span was observed. Further, the HSPB1 mutant gene induced an obvious loss of motor activity when expressed in Drosophila neurons. Moreover, suppression of histone deacetylase 6 (HDAC6) expression, which has critical roles in HSPB1 mutant-induced axonal defects, successfully rescued the motor defects in the HSPB1 mutant Drosophila model.

Efficacy of a Web-Based Screening and Brief Intervention to Prevent Problematic Alcohol Use in Korea: Results of a Randomized Controlled Trial.

BACKGROUND: Web-based alcohol screenings and brief interventions have been shown to be effective methods for changing drinking behavior. This study evaluated the efficacy of the online-based Brief Empowerment Program for Alcohol-Use Monitor (on-BEAM), a brief intervention applying personalized normative feedback (PNF) and components of motivational interviewing (MI) techniques. METHODS: A community-based, double-blind, parallel-group randomized controlled trial with individual randomization was conducted in Korea (registered at Clinical Research Information Service-KCT0003050). An e-mail about participating in a survey on drinking behavior was sent to 5,684 individuals, aged 20 to 40, that were registered as part of a research panel. Male and female participants with AUDIT-C scores of ≥4 and ≥3, respectively, were randomly assigned to either an intervention (received a drinking behavior assessment and the results with normative feedback) or control group (assessment and results without normative feedback). To evaluate the effects of the intervention with 2 sessions over the course of a month, a follow-up assessment was performed online 4 weeks after completion of the intervention. The main outcome was the number of standard drinks consumed during the past week measured using the timeline followback method. The rate ratios (RRs) were calculated to test the effects of the intervention. RESULTS: In total, 1,496 participants were randomized and 93% of them followed up. The intervention group reported consuming less alcohol during the past week (RR = 0.13; p = 0.012) than the control group. Additionally, the intervention group had fewer binge drinkers (RR = 0.69; p < 0.001) and a lower AUDIT-C score (RR = 0.59; p = 0.009) than the control group. CONCLUSIONS: The web-based intervention, on-BEAM, which applies PNF and MI components related to high-risk drinking reduced the amount of alcohol consumption in our study population. Further research is needed to determine the duration of on-BEAM's effects and evaluate its effectiveness in the real world.

Cyclophilin 1 (Cyp1) mutation ameliorates oxidative stress-induced defects in a Drosophila DJ-1 null mutant.

Drosophila cyclophilin 1 (Cyp1) is a structural and functional homolog of mammalian cyclophilin D (CypD), a unique mitochondrial cyclophilin (Cyp) that regulates the inner mitochondrial membrane permeability transition and cell survival under cellular stresses such as oxidative damage. In this study, we generated and characterized a Drosophila Cyp1 mutant. Cyp1 mutant flies successfully developed into adults and showed no significant defects in mitochondrial morphology, function, and content. However, oxidative damage significantly decreased in Cyp1 mutant flies, and inhibition of Cyp1 expression substantially increased the survival under various oxidative stress paradigms. Moreover, Cyp1 mutation successfully ameliorated survival rates, locomotor activity, and dopaminergic neuron quantity in a Drosophila DJ-1 mutant under oxidative stress, further confirming the protective role of Cyp1 mutation against oxidative stress. In conclusion, these results suggest Cyp1 and its human homolog CypD as putative molecular targets for the treatment of DJ-1 deficiency-associated diseases, including Parkinson's disease.

Improvement of erectile dysfunction by the active pepide from Urechis unicinctus by high temperature/pressure and ultra - wave assisted lysis in Streptozotocin Induced Diabetic Rats.

INTRODUCTION: We investigate the effect of active peptide from Urechis unicinctus (UU) by high temperature/pressure and ultra-wave assisted lysis on erectile dysfunction in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Forty 12-week-old Sprague-Dawley rats were used in this study. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (50mg/kg). One week later, the diabetic rats were randomly divided into four groups: normal control, untreated diabetes control, and groups treated with 100 or 500mg/kg/d UU peptide. Rats were fed with UU peptide by intragastric administration for 8 weeks. After 8 weeks, penile hemodynamic function was evaluated in all groups by measuring the intracavernosal pressure after electrostimulating the cavernous nerve. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) activities were measured and endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) protein expression. was determined by Western blot. RESULTS: Maximum intracavernosal pressure in diabetic control rats decreased significantly compared to normal control rats, and was increased significantly compared to untreated diabetic rats after UU peptide supplementation. Treatment with the higher dose of UU peptide significantly increased the NO and cGMP levels compared with the diabetic control group. Decreased activity and expression eNOS and nNOS were found in the diabetic rats compared with the normal control group. Decreased eNOS and nNOS in diabetic rats were improved by UU peptide administration. CONCLUSIONS: Active peptide from UU ameliorates erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction.

Extracellular synthesis of gold bionanoparticles by Nocardiopsis sp. and evaluation of its antimicrobial, antioxidant and cytotoxic activities.

Advancement of biological process for the synthesis of bionanoparticles is evolving into a key area of research in nanotechnology. The present study deals with the biosynthesis, characterization of gold bionanoparticles by Nocardiopsis sp. MBRC-48 and evaluation of their antimicrobial, antioxidant and cytotoxic activities. The gold bionanoparticles obtained were characterized by UV-visible spectroscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray analysis and transmission electron microscopy (TEM). The synthesized gold bionanoparticles were spherical in shape with an average of 11.57 ± 1.24 nm as determined by TEM and dynamic light scattering (DLS) particle size analyzer, respectively. The biosynthesized gold nanoparticles exhibited good antimicrobial activity against pathogenic microorganisms. It showed strong antioxidant activity as well as cytotoxicity against HeLa cervical cancer cell line. The present study demonstrated the potential use of the marine actinobacterial strain of Nocardiopsis sp. MBRC-48 as an important source for gold nanoparticles with improved biomedical applications including antimicrobial, antioxidant as well as cytotoxic agent.

In vitro induction of apoptosis by isosclerone from marine-derived fungus Aspergillus fumigatus.

In the present study, we investigated the apoptotic effects of isosclerone from marine-derived fungi on human breast cancer MCF-7 cells. Treatment with isosclerone exhibited a characteristic feature of apoptosis including significant cytotoxicity and DNA fragmentation in cancer cells. In addition, The apoptosis induction abilities of the isosclerone was studied by analyzing the expression of caspase-3, -8 and -9, Bcl-2 family, NF-κ-B P50, P65, and IKK proteins. Western blot and RT-PCR analysis have indicated that isosclerone induce cancer cells apoptosis through down-regulated Bcl-2 family and up-regulated caspases, and activating the NF-κ-B signaling pathway. Our data demonstrate that isosclerone specifically binds to crystal structure of apoptosis regulator BCL-2 and pseudo-activated procaspase-3 proteins through down-regulated Bcl-2 family and up-regulated caspases, and activating the NF-κ-B signaling pathway. Our proof-of-principle study should have a positive impact on future drug discovery.

Anti-HIV-1 activity of phlorotannin derivative 8,4‴-dieckol from Korean brown alga Ecklonia cava.

8,4‴-dieckol is a natural product which has been isolated from brown alga, Ecklonia cava. This polyphenolic compound is a phlorotannin derivative with a broad range of bioactivities. Its inhibitory activity on human immunodeficiency virus type-1 (HIV-1) was tested and the results indicated that 8,4‴-dieckol inhibited HIV-1 induced syncytia formation, lytic effects, and viral p24 antigen production at noncytotoxic concentrations. Furthermore, it was found that 8,4‴-dieckol selectively inhibited the activity of HIV-1 reverse trancriptase (RT) enzyme with 91% inhibition ratio at the concentration of 50 µM. HIV-1 entry was also inhibited by 8,4‴-dieckol. According to data from this study, 8,4‴-dieckol is an effective compound against HIV-1 with high potential for further studies. These results suggest that it might be used as a drug candidate for the development of new generation therapeutic agents, although further studies on the mechanism of inhibition should be addressed.

Development and Validation of the Therapeutic Communication Scale in Nursing Students.

This study aimed to develop and validate a scale for measuring the therapeutic communication of nursing students. The scale development and evaluation study was conducted based on the scale development guidelines of DeVellis. A 47-item instrument was developed based on a review of the literature and interviews with 16 experts. Content validity was evaluated by ten nursing scholars, and the number of items was reduced to 35. The scale was administered to 352 nursing students from three regions in South Korea in 2022. Exploratory factor analysis and confirmatory factor analysis were performed on the scale items. Convergent validity, discriminant validity, and internal consistency reliability of the scale were evaluated. The factor analysis resulted in 15 items and two factors: relationship building and problem solving. Confirmatory factor analysis and evaluation of convergent and discriminant validity provided support for the validity of the two-factor Therapeutic Communication Scale in nursing students. The total scale demonstrated good internal consistency, with a McDonald's omega (ω) of 0.89. The Therapeutic Communication Scale is a reliable and valid measure that can be used to assess nursing students' therapeutic communication competence related to patient-centered nursing and provide foundational data to improve such skills.

Subgroups of depressive symptoms in Korean police officers: A latent class analysis.

The prevalence of depressive symptoms is common among police officers; however, studies that identify the patterns of depressive symptoms in police officers and occupational characteristics related to the specific subgroups of depressive symptoms are scarce. A total of 493 police officers in South Korea participated in this descriptive cross-sectional study between October and December 2019. Depressive symptoms were measured using the Patient Health Questionnaire-9. Latent class analysis was used to identify the subgroups of depressive symptoms. To identify the characteristics and predictors of the subgroup, χ2 tests, analysis of variance, and multinomial logistic regression analysis were performed. Four latent classes of depressive symptoms were identified: "at-risk" (10.8%), "anhedonic" (21.5%), "somatic" (17.2%), and "minimal" (50.5%). Compared to the minimal group, drinking behaviors were higher in the at-risk group (odds ratio [OR] = 1.10, 95% confidence interval [CI] [1.03, 1.11]), and working hours were greater in the somatic group (OR = 1.01, 95% CI [1.00, 1.02]). Additionally, sleep quality (OR = 1.35, 95% CI [0.82, 2.22]) and fatigue (OR = 1.02, 95% CI [1.00, 1.04]) were found to be related in the anhedonic group. This study identified the heterogeneity of depressive symptoms among police officers. It is necessary to accurately identify the factors associated with the depression subgroups of police officers to develop support strategies and prevent an increase in their depression severity. The association between risk factors such as working hours and drinking behaviors might inform strategies to reduce depression in police offers.

PINK1 and Parkin Ameliorate the Loss of Motor Activity and Mitochondrial Dysfunction Induced by Peripheral Neuropathy-Associated HSPB8 Mutants in Drosophila Models.

Charcot-Marie-Tooth disease (CMT) is a group of inherited peripheral nerve disorders characterized by progressive muscle weakness and atrophy, sensory loss, foot deformities and steppage gait. Missense mutations in the gene encoding the small heat shock protein HSPB8 (HSP22) have been associated with hereditary neuropathies, including CMT. HSPB8 is a member of the small heat shock protein family sharing a highly conserved α-crystallin domain that is critical to its chaperone activity. In this study, we modeled HSPB8 mutant-induced neuropathies in Drosophila. The overexpression of human HSPB8 mutants in Drosophila neurons produced no significant defect in fly development but led to a partial reduction in fly lifespan. Although these HSPB8 mutant genes failed to induce sensory abnormalities, they reduced the motor activity of flies and the mitochondrial functions in fly neuronal tissue. The motor defects and mitochondrial dysfunction were successfully restored by PINK1 and parkin, which are Parkinson's disease-associated genes that have critical roles in maintaining mitochondrial function and integrity. Consistently, kinetin riboside, a small molecule amplifying PINK1 activity, also rescued the loss of motor activity in our HSPB8 mutant model.

Antioxidant peptides from protein hydrolysate of microalgae Navicula incerta and their protective effects in HepG2/CYP2E1 cells induced by ethanol.

Marine microalgae have been reported as valuable new sources of pharmacologically active compounds and there are now numerous commercial applications of microalgae. Hence, in this study we evaluated the protective effects of peptides purified from marine microalgae, Navicula incerta, against alcohol-induced damage in HepG2/CYP2E1 cells. To obtain bioactive peptides from microalgae, N. incerta was hydrolysed using various enzymes (alcalase, α-chymotrypsin, neutrase, papain, pepsin, pronase-E and trypsin), and the hydrolysates were evaluated for cytoprotective activity. Among them, papain-derived hydrolysate exhibited higher antioxidant activities than those of other enzymes. Therefore, papain hydrolysate was purified in order to obtain potent antihepatotoxic and antioxidative peptides. The amino acid sequences of the purified peptides were analysed as; NIPP-1 (Pro-Gly-Trp-Asn-Gln-Trp-Phe-Leu) with molecular mass 1 171 Da, and NIPP-2 (Val-Glu-Val-Leu-Pro-Pro-Ala-Glu-Leu) with molecular mass 1108 Da. Furthermore, this study demonstrated that NIPP-1 and NIPP-2 peptides inhibited ethanol-induced cytotoxicity in HepG2/CYP2E1 cells.

Factors Affecting the Deterioration of the Physical Health Status of Taxi Drivers by Age Group.

With the rapidly aging population, taxi drivers are aging at a fast pace, and competition in the taxi industry is intensifying due to the emergence of various transportation platforms. A descriptive secondary data study was conducted (on a total of 936 subjects) to determine the factors affecting the deterioration of taxi drivers' physical health status (PHS) according to their age group. The increased incidence of chronic diseases and cognitive decline among taxi drivers aged 55−64 years had the greatest influence on the deterioration of their PHS. Driver obesity was more likely to be related to deterioration of the PHS in the drivers aged 55−64 years (OR: 2.459, <0.001) and 35−54 years (OR: 2.133, <0.001). Among the financial factors, a driver's income and their number of dependent family members were correlated with the deterioration of the PHS for drivers aged 55 years or over. Therefore, chronic diseases, obesity and cognitive decline were related with deterioration of the physical health status. This suggests that attention should be paid to healthcare policies not only for the elderly aged over 65 years but also those aged 50 to 64 years, i.e., middle-aged people at the beginning of the transition to old age.

Pyruvate Dehydrogenase Kinase Protects Dopaminergic Neurons from Oxidative Stress in Drosophila DJ-1 Null Mutants.

DJ-1 is one of the causative genes of early-onset familial Parkinson's disease (PD). As a result, DJ-1 influences the pathogenesis of sporadic PD. DJ-1 has various physiological functions that converge to control the levels of intracellular reactive oxygen species (ROS). Based on genetic analyses that sought to investigate novel antioxidant DJ-1 downstream genes, pyruvate dehydrogenase (PDH) kinase (PDK) was demonstrated to increase survival rates and decrease dopaminergic (DA) neuron loss in DJ-1 mutant flies under oxidative stress. PDK phosphorylates and inhibits the PDH complex (PDC), subsequently downregulating glucose metabolism in the mitochondria, which is a major source of intracellular ROS. A loss-of-function mutation in PDK was not found to have a significant effect on fly development and reproduction, but severely ameliorated oxidative stress resistance. Thus, PDK plays a critical role in the protection against oxidative stress. Loss of PDH phosphatase (PDP), which dephosphorylates and activates PDH, was also shown to protect DJ-1 mutants from oxidative stress, ultimately supporting our findings. Further genetic analyses suggested that DJ-1 controls PDK expression through hypoxia-inducible factor 1 (HIF-1), a transcriptional regulator of the adaptive response to hypoxia and oxidative stress. Furthermore, CPI-613, an inhibitor of PDH, protected DJ-1 null flies from oxidative stress, suggesting that the genetic and pharmacological inhibition of PDH may be a novel treatment strategy for PD associated with DJ-1 dysfunction.

Maternal Exposure to Bisphenol A Impacts on Fecundity in F1 and F2 Generations in Drosophila melanogaster.

In previous reports, bisphenol A (BPA) exposure affects reproductive function in Drosophila melanogaster females. To test the maternal effect of BPA exposure on fly reproductive function, F0 mothers were exposed to 0, 0.1, 1, and 10 mg/L of BPA and the fecundity in F1 and F2 generations were checked. In this experiment, 1 and 10 mg/L BPA significantly decreased the fecundity of F1 females. Moreover, 0.1 and 1 mg/L BPA substantially reduced egg production in the F2 generation. These results suggested that maternal exposure to BPA at enviromentally relavant concnetrations reduces reproductive function in Drosophila melanogaster females and that this effect is transgenerational.

Comparison of Physical, Occupational, and Sociocognitive Characteristics of Corporate and Private Taxi Drivers in Korea.

Taxis are a form of public transport which is very closely related to the safety of the public. Although private and corporate taxis have quite different characteristics, there have only been a few studies comparing the characteristics of corporate and private taxis. Moreover, among various characteristics, research was conducted mainly focusing on occupational characteristics. This study was undertaken to compare various physical, occupational, and sociocognitive characteristics of corporate and private taxi drivers. A descriptive cross-sectional study was conducted from 22 August to 11 September 2018. The subjects of this study were 960 corporate and private taxi drivers over 30 years old in Seoul to compare the means and association between private and corporate taxi drivers' characteristics. In terms of the physical characteristics, corporate taxi drivers' general physical health status was worse. In terms of the occupational characteristics, corporate taxi drivers had a high working intensity, and the incidence rate of traffic accidents and near misses was also high. This comparison of the characteristics of corporate and private taxis is expected to serve as evidence for developing tailored policies and programs to improve the health of corporate and private taxi drivers.

Risk Factors Influencing Cyberbullying Perpetration among Middle School Students in Korea: Analysis Using the Zero-Inflated Negative Binomial Regression Model.

This cross-sectional descriptive study identified risk factors and predictors related to the perpetration of and potential for cyberbullying among adolescents, respectively. The analysis included a zero-inflated negative binomial regression model. Data were assessed from 2590 middle-school student panels obtained during the first wave of the Korean Child and Youth Panel Survey 2018. Of these respondents, 63.7% said they had not experienced the perpetration of cyberbullying. However, a subsequent count model analysis showed that several factors were significantly associated with cyberbullying, including offline delinquency, aggression, smartphone dependency, and smartphone usage on weekends (either 1-3 h or over 3 h). A logit model analysis also showed several predictive factors that increased the likelihood of cyberbullying, including gender (boys), offline delinquency, aggression, smartphone usage during weekdays (1-3 h), computer usage during weekends (1-3 h), and negative parenting. These identified risks and predictors should be useful for interventions designed to prevent the perpetration of cyberbullying among middle school students.

Gambling Subgroups among Korean Out-of-school Adolescents.

PURPOSE: The number of Korean adolescents engaging in gambling is increasing, especially among out-of-school adolescents. This study aimed to identify patterns of gambling activities and factors related to specific subgroups of out-of-school adolescent gambling activities. METHODS: This descriptive study analyzed secondary data from the 2015 Korea Youth Gambling Problem Survey, including 1,200 out-of-school adolescents. Latent class analysis was conducted to identify patterns of gambling activities. The factors related to gambling subgroups were verified with multinomial logistic regression. RESULTS: Three latent classes of gambling activities were identified: rarely gambling (RG), immediate gain gambling (IGG), and broad gambling (BG). These subgroups differed significantly in terms of gender, age at and type of first gambling experience, number and type of gambling activities, gambling frequency, time and money spent on gambling, problem gambling severity, and motivation for gambling. Compared to the RG subgroup, both the IGG and BG subgroups were strongly associated with an older age at the first gambling experience. CONCLUSION: Out-of-school adolescents who first gambled at an older age and who gambled mainly in order to gain money immediately were at risk of problem gambling. Developing strategies for early screening and referral to professionals is necessary to prevent gambling problems from worsening.

The Gambling Factors Related with the Level of Adolescent Problem Gambler.

The purpose of this study was to investigate the gambling factors related with the gambling problem level of adolescents to provide basic information for the prevention of adolescent gambling problems. The data was drawn from the 2015 Survey on Youth Gambling Problems of the Korea Center on Gambling Problems for Korean students in grades 7-11 (ages 13-17 years) and included 14,011 study subjects (average age 14.9 years, 52.5% male). The lifetime gambling behavior experience was 42.1%, and 24.2% had a gambling behavior experience within the past three months. The past three-month prevalence of problem gambling was 1.1%. The gambling factors related with the level of adolescent problem gambling include the presence of nearby gambling facilities, having personal relationships with people that gamble, a higher number of experienced gambling behaviors, male adolescents, and a greater amount of time spent gambling. To the best of our knowledge, this study is the first report to identify gambling factors related with the level of adolescent problem gambling in Korean adolescents using national data. These findings suggest that gambling prevention efforts must consider not only access to individual adolescents as early intervention, but also environmental strategies such as accessibility regulations and alternative activities.