Effects of Coronavirus Disease 2019 on Prevalence of Acute Respiratory Viruses: Changes during the Pandemic.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic may have influenced the prevalence and seasonality of acute respiratory viral infections. The aim of the study was to investigate the prevalence of all viruses causing acute viral respiratory infections before and after social distancing measures were lifted. Methods: Cross-sectional study where outpatients and inpatients at Kyunghee University Hospital were examined. From January 2021 to December 2022, respiratory samples were analyzed using multiplex reverse transcriptase real-time polymerase chain reaction. Results: Of 3953 samples obtained, 412 (10.42%) were positive for acute respiratory viral infection, and 502 viruses were detected. The number of viral infections increased from 184 in 2021 to 318 in 2022. Human metapneumovirus was detected from August to November 2022. Human bocavirus (HBoV) was frequently detected from April to June 2021; however, in 2022, HBoV was frequently detected from July to October. Human parainfluenza virus 3 was rarely detected after its initial frequent detection from October to December 2021 but was continuously observed after frequent detection in September 2022. Co-infection occurred in 78 (18.9%) cases. The most common combination of simultaneous infections was human rhinovirus-HBoV (n = 30, 38.5%). Conclusions: During the COVID-19 pandemic, the incidence of acute respiratory viral infection decreased significantly but increased in 2022 when measures were lifted. The prevalence and seasonality of respiratory viral infections have changed since the pandemic. Our findings contribute to the prediction of an effective response to changes in the prevalence of respiratory viruses.

Surgical Outcomes of Extensive Dome-Like Laminoplasty Using En Bloc Resection of C2 Inner Lamina for Patients With Severe Cord Compression Behind C2 Body.

STUDY DESIGN: A retrospective, single-center study. OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a newly developed extensive dome-like laminoplasty using en bloc resection of the C2 inner lamina in patients with severe cord compression behind the C2 body. SUMMARY OF BACKGROUND DATA: A surgery for severe cord compression behind C2 body is challenging for spinal surgeons. To date, there has been no established solution for severe cord compression behind the C2 body. MATERIALS AND METHODS: Patients with severe cord compression behind the C2 body who underwent posterior surgery consecutively were enrolled. Extensive dome-like laminoplasty that was newly developed was performed to remove en bloc removal of the C2 inner lamina were performed. Preoperative and postoperative canal diameters behind the C2 and mean removed area of the C2 inner lamina were measured using MRI and CT scan. Clinical and radiographic parameters were assessed preoperative and postoperative periods. In addition, perioperative complications were analyzed. RESULTS: A total of 36 patients underwent extensive dome-like laminoplasty and their diagnoses were ossification of the posterior longitudinal ligament (OPLL, 66.7%) and congenital stenosis with spondylosis (33.3%). The mean canal diameter behind the C2 increased from 9.85 (2.28) mm preoperatively to 19.91 (3.93) mm at the last follow-up ( P <0.001). Clinically, neck and arm visual analog scale, Japanese Orthopaedic Association score, and neck disability index significantly improved at postoperative 1 month ( P <0.05), and the scores were maintained until the last follow-up. No meaningful radiographic changes occurred after the surgeries. During the procedures, there were no particular complications, but one patient showed deteriorated myelopathic symptoms and underwent additional C1-C2 decompressive surgery. CONCLUSIONS: After extensive dome-like laminoplasty, surgical outcomes are satisfactory, and complications are rare. This technique may be a viable option for patients with severe cord compression behind the C2 body. LEVEL OF EVIDENCE: Level IV.

Evaluation of Physical Properties of Coated Polydioxanone Threads.

BACKGROUND: Using a thread for wound closure promotes healing and minimizes contamination by foreign substances. Threads have also been employed in esthetic surgery; however, functional threads that can improve wrinkles and rejuvenate the skin are required. OBJECTIVE: To evaluate the suitability of polydioxanone threads coated with polyethylene glycol, hyaluronic acid, and amino acids for use in the medical field because such formulations are expected to promote regeneration and collagen synthesis. MATERIALS AND METHODS: Physical properties (diameter [ n = 20], tensile strength [ n = 20], strength retention rate [ n = 10], and scanning electron microscopy images) and cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays) of polydioxanone threads coated with polyethylene glycol, hyaluronic acid, and amino acids were assessed and compared with those of uncoated polydioxanone threads. Analyses were performed using IBM SPSS Statistics (Statistical significance; p values <.05). RESULTS: The size standards for tensile strength (≥63.5 N) and diameter (average 0.570-0.610 mm) were met. There were no differences in the physical properties of the coated and uncoated threads; however, the biocompatibility of coated threads was high owing to low cytotoxicity. CONCLUSION: Threads coated with materials that can promote regeneration are suitable for use in the medical field.

A retrospective study on the status of sexually transmitted co-infections in university hospitals in Korea from 2017 to 2021.

Background: The prevalence of sexually transmitted infections (STIs) remains high worldwide. Despite the worldwide increase in the incidence of STIs every year, there are few reports on the frequency of STIs with different pathogens according to age and gender. Accordingly, a study was conducted to determine trends in co-infection with STIs by age and gender in Cheonan, South Korea from 2017 to 2021. Objectives: To identify trends by age or sex in co-infection of STIs in this region. Design: A retrospective study was conducted on clinical samples examined at Dankook University Hospital from January 2017 to November 2021. A total of 3297 specimens were collected from patients visiting Dankook University Hospital (Cheonan, Korea), and statistical analysis was performed on patients ranging in age from 1 day to 93 years. Methods: Multiplex polymerase chain reaction, the most efficient method to diagnose a bacterial infection, was performed using an MJ Research PTC-200 Thermal Cycler (Marshall Scientific, Richmond, VA, USA) and a Seeplex STD Detection Kit (Seegene, Seoul, Republic of Korea). The co-infection rate with STI pathogens was analyzed according to age and sex. Results: Of the 3297 clinical samples, 1017 (30.9%) tested positive for sexually transmitted pathogens, ranging from one to six co-infections. Analysis of the co-infection rate by age revealed that the average age gradually decreased as the total number of co-infection pathogens increased. The co-infection percentage and age distribution of STIs differed according to sex. Co-infection was more prevalent in female patients. Furthermore, co-infection in male patients occurred frequently in the 30-39-year-old group, while those in female patients occurred in the 20-29- and 30-39-year-old groups. Conclusion: Our statistical analysis showed that STI co-infections were more common among younger than older people. Therefore, it helps in recognizing STIs at a young age and provides possible indicator data to prevent STIs at a young age. In addition, further research is needed on co-infection in other regions.

Sensorimotor adaptation in spatial orientation task: a fNIRS study.

In sensorimotor conflicts, the brain forms and updates a new sensorimotor relationship through sensorimotor integration. As humans adapt to new sensorimotor mapping, goal-directed movements become increasingly precise. Using functional near-infrared spectroscopy, we investigated the changes in cortical activity during sensorimotor adaptation in a spatial orientation task with sensorimotor conflict. Individuals performed a reversed spatial orientation training in which the visual feedback guiding hand movements was reversed. We measured cortical activity and spatial orientation performance, including the response time, completion number, error, and accuracy. The results revealed the continuous activation in the left SMG during sensorimotor adaptation and decreased activation in the right SAC, AG and SMG after sensorimotor adaptation. These findings indicated the contribution of the left SMG to sensorimotor adaptation and the improved efficiency of cortical activity after sensorimotor adaptation, respectively. Our studies suggest the neural mechanisms related to sensorimotor adaptation to a reversed spatial orientation task.

Difference between Anterior and Posterior Cord Compression and Its Clinical Implication in Patients with Degenerative Cervical Myelopathy.

In degenerative cervical myelopathy (DCM), the low anteroposterior compression ratio of the spinal cord is known to be associated with a neurologic deficit. However, there is little detailed analysis of spinal cord compression. Axial magnetic resonance images of 183 DCM patients at normal C2-C3 and maximal cord compression segments were analyzed. The anterior (A), posterior (P), and anteroposterior length and width (W) of the spinal cord were measured. Correlation analyses between radiographic parameters and each section of Japanese Orthopedic Association (JOA) scores and comparisons of the patients divided by A (below or above 0, 1, or 2 mm) were performed. Between C2-C3 and maximal compression segments, the mean differences of A and P were 2.0 (1.2) and 0.2 (0.8) mm. The mean anteroposterior compression ratios were 0.58 (0.13) at C2-C3 and 0.32 (0.17) at maximal compression. The A and A/W ratio were significantly correlated with four sections and the total JOA scores (p < 0.05), but the P and P/W ratio did not demonstrate any correlations. Patients with A < 1 mm had significantly lower JOA scores than those with A ≥ 1 mm. In patients with DCM, spinal cord compression occurs mainly in the anterior part and the anterior cord length of <1 mm is particularly associated with neurologic deficits.

Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation.

Human skin is constructed with many proteins such as collagen and elastin. Collagen and elastin play a key role in providing strength and elasticity to the human skin and body. However, damage to collagen causes various symptoms such as wrinkles and freckles, which suggests that they are important to maintain skin condition. Extrinsic or intrinsic skin aging produces an excess of skin destructive factors such as tumor necrosis factor (TNF)-α, which is a major mediator of the aging process. In aged skin, TNF-α provokes the generation of intracellular ROS (reactive oxygen species). It triggers the excessive secretion of MMP-1, which is a collagen-degrading enzyme that causes the collapse of skin collagen. Therefore, we aimed to search for a natural-product-derived candidate that inhibits the skin damage caused by TNF-α in human dermal fibroblasts. In this study, the protective effect of withagenin A diglucoside (WAD) identified from Withania somnifera against TNF-α-stimulated human dermal fibroblasts is investigated. W. somnifera (Solanaceae), well-known as 'ashwagandha', is an Ayurvedic medicinal plant useful for promoting health and longevity. Our experimental results reveal that WAD from W. somnifera suppresses the generation of intercellular ROS. Suppressing intracellular ROS generation inhibits MMP-1 secretion and the collapse of type 1 collagen. The effect of WAD is shown to depend on the inhibition of MAPK phosphorylation, Akt phosphorylation, c-Jun phosphorylation, COX-2 expression, and NF-κB phosphorylation. Further, WAD-depressed expression of the pro-inflammatory cytokines IL-6 and IL-8 triggers various inflammatory reactions in human skin. These findings suggest that WAD has protective effects against skin damage. Accordingly, our study provides experimental evidence that WAD can be a potential agent that can be applied in various industrial fields, such as cosmetics and pharmaceuticals related to skin aging.

Coinfections with multiple sexually transmitted pathogens in Republic of Korea, 2018-2020.

BACKGROUND: Sexually transmitted infections (STIs) can have serious consequences, and the global STI incidence remains high. However, there is little information on the frequency of STIs with multiple pathogens according to age. Accordingly, we conducted a study to determine the trends of coinfection with sexually transmitted pathogens according to age in the Republic of Korea from 2018 to 2020. METHODS: From January 2018 to December 2020, 65,191 samples of swab, urine, and other types submitted for STI screening were obtained from U2Bio Co. Ltd. (Seoul, Republic of Korea). Multiplex polymerase chain reaction, a sensitive and rapid method for simultaneous detection of STIs caused by multiple different pathogens, was performed using an AccuPower STI4C-Plex Real-Time PCR kit, AccuPower STI8A-Plex Real-Time PCR kit, and AccuPower STI8B-Plex Real-Time PCR kit with an Exicycler 96 Real-Time Quantitative Thermal Block. RESULTS: Of the 65,191 samples tested, 35,366 (54.3%) tested positive for one or more sexually transmitted pathogens. The prevalence of coinfections with two or more sexually transmitted pathogens was inversely proportional to age. Furthermore, the rates of coinfection with sexually transmitted pathogens and age distribution differed according to sex and the sexually transmitted pathogen type. CONCLUSION: This study confirmed that a significant proportion of patients with STIs are coinfected with multiple pathogens. Public health managers could use these results to recognize and prevent STIs according to age.

Association among sentinel surveillance, meteorological factors, and infectious disease in Gwangju, Korea.

The outbreak of new infectious diseases is threatening human survival. Transmission of such diseases is determined by several factors, with climate being a very important factor. This study was conducted to assess the correlation between the occurrence of infectious diseases and climatic factors using data from the Sentinel Surveillance System and meteorological data from Gwangju, Jeollanam-do, Republic of Korea. The climate of Gwangju from June to September is humid, with this city having the highest average temperature, whereas that from December to February is cold and dry. Infection rates of Salmonella (temperature: r = 0.710**; relative humidity: r = 0.669**), E. coli (r = 0.617**; r = 0.626**), rotavirus (r = - 0.408**; r = - 0.618**), norovirus (r = - 0.463**; r = - 0.316**), influenza virus (r = - 0.726**; r = - 0.672**), coronavirus (r = - 0.684**; r = - 0.408**), and coxsackievirus (r = 0.654**; r = 0.548**) have been shown to have a high correlation with seasonal changes, specifically in these meteorological factors. Pathogens showing distinct seasonality in the occurrence of infection were observed, and there was a high correlation with the climate characteristics of Gwangju. In particular, viral diseases show strong seasonality, and further research on this matter is needed. Due to the current COVID-19 pandemic, quarantine and prevention have become important to block the spread of infectious diseases. For this purpose, studies that predict infectivity through various types of data related to infection are important.

Association between climatic factors and respiratory syncytial virus detection rates in Cheonan, Korea.

The use of big data may facilitate the recognition and interpretation of causal relationships between disease occurrence and climatic variables. This study examined the effects of various climatic variables on the seasonal epidemiology of respiratory syncytial virus (RSV) infections in the temperate climate of Korea. Trends in RSV detection were analyzed using 9010 samples tested between January 1, 2012, and December 31, 2018, at Dankook University Hospital in Cheonan, Korea. Seasonal patterns in RSV detection frequency were compared with local climatic variables during the same period. RSV detection rate of 12.8% (n = 1150/9010) was observed, which was higher for RSV-A (7.1%) than RSV-B (5.8%) and RSV-A and RSV-B alternated each year. Children < 1 year exhibited high infection rates with RSV-A (68.5%) and RSV-B (58.7%). RSV-A and RSV-B infection rates in children under 9 years old were 96.2% and 92.1%, respectively. RSV had a significant relationship with several climatic factors. Air temperature, wind chill temperature, and particulate matter concentration were lower on days with a higher frequency of RSV detection. In contrast, atmospheric pressure was higher on days with lower RSV detection. Although the detection rates for RSV-A and RSV-B increased on days with lower air temperatures, those for RSV-B also increased on days with lower wind chill temperatures. Our findings suggest that climatic variables affect the RSV detection rate among children under 10 years of age. The present data may help predict the time when prevention strategies may be the most effective.

Cervical Radiculopathy: Focus on Factors for Better Surgical Outcomes and Operative Techniques.

For patients with cervical radiculopathy, most studies have recommended conservative treatment as the first-line treatment; however, when conventional treatment fails, surgery is considered. A better understanding of the prognosis of cervical radiculopathy is essential to provide accurate information to the patients. If the patients complain of persistent and recurrent arm pain/numbness not respond to conservative treatment, or exhibit neurologic deficits, surgery is performed using anterior or posterior approaches. Anterior cervical discectomy and fusion (ACDF) has historically been widely used and has proven to be safe and effective. To improve surgical outcomes of ACDF surgery, many studies have been conducted on types of spacers, size/height/position of cages, anterior plating, patients' factors, surgical techniques, and so forth. Cervical disc replacement (CDR) is designed to reduce the incidence of adjacent segment disease during long-term follow-up by maintaining cervical spine motion postoperatively. Many studies on excellent indications for the CDR, proper type/size/shape/height of the implants, and surgical techniques were performed. Posterior cervical foraminotomy is a safe and effective surgical option to avoid complications associated with anterior approach and fusion surgery. Most recent literature demonstrated that all three surgical techniques for patients with cervical radiculopathy have clear advantages and disadvantages and reveal satisfactory surgical outcomes under a proper selection of patients and application of appropriate surgical methods. For this, it is important to fully understand the factors for better surgical outcomes and to adequately practice the operative techniques for patients with cervical radiculopathy.

Mycoplasma genitalium and Mycoplasma hominis infection in south Korea during 2018-2020.

BACKGROUND AND OBJECTIVES: Sexually transmitted infections (STIs) can remain undetected and untreated; therefore, rapid diagnosis and treatment of STIs are important. Mycoplasma genitalium (MG), Mycoplasma hominis (MH), and Ureaplasma urealyticum are sexually transmitted pathogens that cause asymptomatic, organ-specific, and chronic infections, thereby posing a threat to community health. Therefore, we investigated the epidemiological trends of MG and MH infections in South Korea for rapid diagnosis and treatment. MATERIALS AND METHODS: From September 2018 to December 2020, samples (catheter, pus, tissue, swab, and urine) were collected from outpatients of hospitals in South Korea for molecular biological venereal disease testing. DNA was extracted and analyzed using real-time polymerase chain reaction. RESULTS: Of the 59,381 samples analyzed, 8.78% (n=5,215) were positive for MG and MH. The MH positivity rate (5.51%, n=3,273) was higher than the MG positivity rate (3.27%, n=1,942). MG and MH positivity rates were the highest in patients aged <19 years. Men had higher MG positivity rate, whereas women had higher MH positivity rates. Furthermore, the MG-positivity rate was the highest in the swab samples of both men and women, whereas that of MH was the highest in the urine samples of men and swab samples of women. CONCLUSION: We identified the differences between MG and MH positivity rates based on sex, specimen, and age. Our findings can provide information for strategies that protect public health and reduce STI incidence and transmission.

Effects of Dual-Task Training on Gait Parameters in Elderly Patients with Mild Dementia.

This study aimed to investigate the effectiveness of dual-task training (DTT) compared to single-task training (STT), on gait parameters in elderly patients with mild dementia (MD). Twenty-four elderly patients with MD were randomly assigned to the DTT (n = 13) or the STT group (n = 11). The DTT group performed a specific cognitive-motor DTT, while the STT group received only motor task training. Both training sessions lasted 8 weeks, with a frequency of 3 days per week, and the cognitive functions and gait parameters were measured. A statistically significant interaction effect was found between the two groups in stride length, stride velocity, cadence, step length, swing phase, stance phase, and double support phase (p < 0.05). After 8 weeks, the DTT group showed significant improvement in spatiotemporal parameters, except for the kinematic parameters (p < 0.05). In the between-group analysis, the DTT group showed more improvement than the STT group in stride velocity, step length, swing phase, stance phase, and double support (p < 0.05). These findings suggest that improvements in spatiotemporal gait parameters after DTT are reported in patients with MD. Our results can guide therapists to include dual tasks in their gait rehabilitation programs for the treatment of mild dementia.

Withasomniferol D, a New Anti-Adipogenic Withanolide from the Roots of Ashwagandha (Withania somnifera).

Withania somnifera (Solanaceae), well-known as 'Indian ginseng' or 'Ashwagandha', is a medicinal plant that is used in Ayurvedic practice to promote good health and longevity. As part of an ongoing investigation for bioactive natural products with novel structures, we performed a phytochemical examination of the roots of W. somnifera employed with liquid chromatography-mass spectrometry (LC/MS)-based analysis. The chemical analysis of the methanol extract of W. somnifera roots using repeated column chromatography and high-performance liquid chromatography under the guidance of an LC/MS-based analysis resulted in a new withanolide, withasomniferol D (1). The structure of the newly isolated compound was elucidated by spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high-resolution (HR) electrospray ionization (ESI) mass spectroscopy, and its absolute configuration was established by electronic circular dichroism (ECD) calculations. The anti-adipogenic activities of withasomniferol D (1) were evaluated using 3T3-L1 preadipocytes with Oil Red O staining and quantitative real-time polymerase chain reaction (qPCR). We found that withasomniferol D (1) inhibited adipogenesis and suppressed the enlargement of lipid droplets compared to the control. Additionally, the mRNA expression levels of adipocyte markers Fabp4 and Adipsin decreased noticeably following treatment with 25 µM of withasomniferol D (1). Taken together, these findings provide experimental evidence that withasomniferol D (1), isolated from W. somnifera, exhibits anti-adipogenic activity, supporting the potential application of this compound in the treatment of obesity and related metabolic diseases.

Selenium Nanoparticles as Candidates for Antibacterial Substitutes and Supplements against Multidrug-Resistant Bacteria.

In recent years, multidrug-resistant (MDR) bacteria have increased rapidly, representing a major threat to human health. This problem has created an urgent need to identify alternatives for the treatment of MDR bacteria. The aim of this study was to identify the antibacterial activity of selenium nanoparticles (SeNPs) and selenium nanowires (SeNWs) against MDR bacteria and assess the potential synergistic effects when combined with a conventional antibiotic (linezolid). SeNPs and SeNWs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), zeta potential, and UV-visible analysis. The antibacterial effects of SeNPs and SeNWs were confirmed by the macro-dilution minimum inhibitory concentration (MIC) test. SeNPs showed MIC values against methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA), and vancomycin-resistant enterococci (VRE) at concentrations of 20, 80, 320, and >320 µg/mL, respectively. On the other hand, SeNWs showed a MIC value of >320 µg/mL against all tested bacteria. Therefore, MSSA, MRSA, and VRSA were selected for the bacteria to be tested, and SeNPs were selected as the antimicrobial agent for the following experiments. In the time-kill assay, SeNPs at a concentration of 4X MIC (80 and 320 µg/mL) showed bactericidal effects against MSSA and MRSA, respectively. At a concentration of 2X MIC (40 and 160 µg/mL), SeNPs showed bacteriostatic effects against MSSA and bactericidal effects against MRSA, respectively. In the synergy test, SeNPs showed a synergistic effect with linezolid (LZD) through protein degradation against MSSA and MRSA. In conclusion, these results suggest that SeNPs can be candidates for antibacterial substitutes and supplements against MDR bacteria for topical use, such as dressings. However, for use in clinical situations, additional experiments such as toxicity and synergistic mechanism tests of SeNPs are needed.

Biological Potential of Polyethylene Glycol (PEG)-Functionalized Graphene Quantum Dots in In Vitro Neural Stem/Progenitor Cells.

Stem cell therapy is one of the novel and prospective fields. The ability of stem cells to differentiate into different lineages makes them attractive candidates for several therapies. It is essential to understand the cell fate, distribution, and function of transplanted cells in the local microenvironment before their applications. Therefore, it is necessary to develop an accurate and reliable labeling method of stem cells for imaging techniques to track their translocation after transplantation. The graphitic quantum dots (GQDs) are selected among various stem cell labeling and tracking strategies which have high photoluminescence ability, photostability, relatively low cytotoxicity, tunable surface functional groups, and delivering capacity. Since GQDs interact easily with the cell and interfere with cell behavior through surface functional groups, an appropriate surface modification needs to be considered to get close to the ideal labeling nanoprobes. In this study, polyethylene glycol (PEG) is used to improve biocompatibility while simultaneously maintaining the photoluminescent potentials of GQDs. The biochemically inert PEG successfully covered the surface of GQDs. The PEG-GQDs composites show adequate bioimaging capabilities when internalized into neural stem/progenitor cells (NSPCs). Furthermore, the bio-inertness of the PEG-GQDs is confirmed. Herein, we introduce the PEG-GQDs as a valuable tool for stem cell labeling and tracking for biomedical therapies in the field of neural regeneration.

Pulveraven A from the fruiting bodies of Pulveroboletus ravenelii induces apoptosis in breast cancer cell via extrinsic apoptotic signaling pathway.

Pulveroboletus ravenelii (Beck. et Curt.) Murr. (Boletaceae), commonly known as Ravenel's bolete, is an edible and medicinal mushroom, and is also used for preparing mushroom-based dyes. As part of a continuing project to discover the bioactive natural products from wild mushrooms, we analyzed the methanol (MeOH) extract of P. ravenelii to identify metabolites with the anticancer activity. Chemical analysis of the MeOH extract combined with liquid chromatography-mass spectrometry (LC-MS) analysis led to the isolation of a phenolic compound, pulveraven A (PA), whose chemical structure was determined using a combination of 1D and 2D NMR and LC-MS analysis. In the present study, we investigated the cytotoxicity and anticancer mechanisms of pulveraven A using human breast cancer (MCF-7) cells, and demonstrated that it reduced cell viability of MCF-7 cells below 50% (71.74 ± 3.61 µM). Annexin V Alexa Fluor 488 binding assay and western blot results revealed that pulveraven A induced apoptotic cell death via the extrinsic apoptosis pathway, as indicated by the activation of initiator caspase-8 and executioner caspase-7. Furthermore, it was accompanied by an increase in the Bax/Bcl-2 ratio. These results suggest that pulveraven A induces apoptosis in breast cancer cells via the extrinsic apoptotic signaling pathway.

Ceria-Incorporated Biopolymer for Preventing Fungal Adhesion.

Although biopolymers are widely used in biomedical fields, the issue of poor antimicrobial properties remains unsolved, leading to a potential increase in infections. Here, ceria nanoparticles (CNPs) were incorporated into a representative biopolymer, poly(methyl methacrylate) (PMMA), for drug-free antimicrobial properties. After characterizing the CNPs and surface/mechanical properties of the CNP-PMMA nanocomposite, antiadhesive effects against Candida albicans, the most common fungal species responsible for fungal infections, were determined using metabolic activity assays, and the underlying microbial antiadhesive mechanism was revealed. Hydrothermally fabricated CNPs showed a size of ∼20 nm with a zeta potential of 12 ± 2.3 mV and showed catalytic properties as a ROS modulator. Successful incorporation of CNPs into PMMA up to 2 wt % was confirmed by EDS analysis. The surface roughness and mechanical properties such as flexural strength and modulus were relatively unchanged up to 2 wt %. In contrast, the surface energy increased, and the Vickers hardness decreased in the 2 wt % PMMA compared with the control. A drop of up to 90% of adherent Candida albicans was observed in CNP-incorporated PMMA, which was confirmed and quantified via fungus staining images. The antiadhesive mechanism was revealed from the direct antimicrobial effects of CNP via the upregulation of the intracellular ROS level. Taken together, the antimicrobial-adhesive properties of the CNP-PMMA nanocomposite suggest the potential usefulness of CNP as a promising drug-free antimicrobial ingredient for biopolymers, which could lead to the prevention of microbial-induced complications in clinical settings.

Identification of bioactive compounds from mulberry enhancing glucose-stimulated insulin secretion.

Previously, we isolated six heterocyclic compounds (1-6) from the fruits of mulberry trees (Morus alba L.) and determined that loliolide affords rat pancreatic islet ß-cell (INS-1) protection against streptozotocin­induced cytotoxicity. In the present study, we further investigated the effect of the six heterocyclic compounds (1-6) on glucose-stimulated insulin secretion (GSIS) in INS-1 cells. Among them, (R)­5­hydroxypyrrolidin­2­one(1) and indole (6) increased GSIS without inducing cytotoxicity. Additionally, compounds 1 and 6 enhanced the phosphorylation of total insulin receptor substrate-2, phosphatidylinositol 3-kinase, and Akt, and activated pancreatic and duodenal homeobox-1, which play a crucial role in ß-cell functions related to insulin secretion. Collectively, these findings indicate that (R)­5­hydroxypyrrolidin­2­one(1) and indole (6), isolated from M. alba fruits, may be beneficial in managing type 2 diabetes.

Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance.

Inhibition of the megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2, also named PTPN9) activity has been shown to be a potential therapeutic strategy for the treatment of type 2 diabetes. Previously, we reported that PTP-MEG2 knockdown enhances adenosine monophosphate activated protein kinase (AMPK) phosphorylation, suggesting that PTP-MEG2 may be a potential antidiabetic target. In this study, we found that phloridzin, isolated from Ulmus davidiana var. japonica, inhibits the catalytic activity of PTP-MEG2 (half-inhibitory concentration, IC50 = 32 ± 1.06 µM) in vitro, indicating that it could be a potential antidiabetic drug candidate. Importantly, phloridzin stimulated glucose uptake by differentiated 3T3-L1 adipocytes and C2C12 muscle cells compared to that by the control cells. Moreover, phloridzin led to the enhanced phosphorylation of AMPK and Akt relevant to increased insulin sensitivity. Importantly, phloridzin attenuated palmitate-induced insulin resistance in C2C12 muscle cells. We also found that phloridzin did not accelerate adipocyte differentiation, suggesting that phloridzin improves insulin sensitivity without significant lipid accumulation. Taken together, our results demonstrate that phloridzin, an inhibitor of PTP-MEG2, stimulates glucose uptake through the activation of both AMPK and Akt signaling pathways. These results strongly suggest that phloridzin could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.