Safety and effectiveness of integrative Korean medicine for the management of patients sustaining injuries in traffic accidents during pregnancy: A retrospective chart review and questionnaire survey.

The number of traffic accidents (TAs) is rising each year, and the severity of injuries can vary. Many people experience limitations in activities of daily living following TAs, affecting their quality of life. In pregnant women, even simple injuries caused by a TA could lead to unfavorable obstetric outcomes. Thus, we conducted a retrospective chart review and follow-up questionnaire survey to assess the safety and effectiveness of integrative Korean medicine (KM) treatment for pregnant women injured in TAs. To assess integrative KM effectiveness, the numeric rating scale (NRS) for TA-related symptoms, neck disability index (NDI) score, Oswestry disability index (ODI) score, shoulder pain and disability index score, Western Ontario and McMaster Universities Arthritis Index score, EuroQol 5-dimension 5-level (EQ-5D-5L) score, and patient global impression of change score were investigated for pregnant women injured in TAs. Additionally, for safety evaluation, obstetric and neonatal outcomes, as well as symptoms related to pregnancy, were assessed. At the end of treatment and follow-up, there were significant reductions in NDI and ODI scores, as well as NRS for neck pain, lower back pain, and headache, compared to scores at baseline. EQ-5D-5L scores significantly increased. A follow-up of 50 patients showed no major differences in obstetric and neonatal outcomes compared to the typical outcomes that occur in pregnant women and neonates. Major improvements were observed in the symptoms of patients who underwent integrative KM treatment after being injured in TAs. The symptoms occurred at a rate similar to those in typical pregnant women, while causality with integrative KM treatment was assessed to be unlikely or unclear. Therefore, integrative KM treatment may be considered an alternative treatment option for pregnant women who currently have limited treatment options.

HSPA9 reduction exacerbates symptoms and cell death in DSS-Induced inflammatory colitis.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that is influenced by various factors, including environmental factors, immune responses, and genetic elements. Among the factors that influence IBD progression, macrophages play a significant role in generating inflammatory mediators, and an increase in the number of activated macrophages contributes to cellular damage, thereby exacerbating the overall inflammatory conditions. HSPA9, a member of the heat shock protein 70 family, plays a crucial role in regulating mitochondrial processes and responding to oxidative stress. HSPA9 deficiency disrupts mitochondrial dynamics, increasing mitochondrial fission and the production of reactive oxygen species. Based on the known functions of HSPA9, we considered the possibility that HSPA9 reduction may contribute to the exacerbation of colitis and investigated its relevance. In a dextran sodium sulfate-induced colitis mouse model, the downregulated HSPA9 exacerbates colitis symptoms, including increased immune cell infiltration, elevated proinflammatory cytokines, decreased tight junctions, and altered macrophage polarization. Moreover, along with the increased mitochondrial fission, we found that the reduction in HSPA9 significantly affected the superoxide dismutase 1 levels and contributed to cellular death. These findings enhance our understanding of the intricate mechanisms underlying colitis and contribute to the development of novel therapeutic approaches for this challenging condition.

Split Proteins and Reassembly Modules for Biological Applications.

Split systems, modular entities enabling controlled biological processes, have become instrumental in biological research. This review highlights their utility across applications like gene regulation, protein interaction identification, and biosensor development. Covering significant progress over the last decade, it revisits traditional split proteins such as GFP, luciferase, and inteins, and explores advancements in technologies like Cas proteins and base editors. We also examine reassembly modules and their applications in diverse fields, from gene regulation to therapeutic innovation. This review offers a comprehensive perspective on the recent evolution of split systems in biological research.

Inhibition of VHL by VH298 Accelerates Pexophagy by Activation of HIF-1α in HeLa Cells.

Autophagy is a pivotal biological process responsible for maintaining the homeostasis of intracellular organelles. Yet the molecular intricacies of peroxisomal autophagy (pexophagy) remain largely elusive. From a ubiquitin-related chemical library for screening, we identified several inhibitors of the Von Hippel-Lindau (VHL) E3 ligase, including VH298, thereby serving as potent inducers of pexophagy. In this study, we observed that VH298 stimulates peroxisomal degradation by ATG5 dependently and escalates the ubiquitination of the peroxisomal membrane protein ABCD3. Interestingly, the ablation of NBR1 is similar to the curtailed peroxisomal degradation in VH298-treated cells. We also found that the pexophagy induced by VH298 is impeded upon the suppression of gene expression by the translation inhibitor cycloheximide. Beyond VHL inhibition, we discovered that roxadustat, a direct inhibitor of HIF-α prolyl hydroxylase, is also a potent inducer of pexophagy. Furthermore, we found that VH298-mediated pexophagy is blocked by silencing HIF-1α. In conclusion, our findings suggest that VH298 promotes pexophagy by modulating VHL-mediated HIF-α transcriptional activity.

Surveillance of wild animals carrying infectious agents based on high-throughput screening platform in the Republic of Korea.

BACKGROUND: Infectious diseases transmitted by wild animals are major threats to public health. This study aimed to investigate the potential of rescued wild animals that died of unknown causes as reservoirs of infectious agents. From 2018 to 2019, 121 dead wild animals (55 birds and 66 mammals) were included in this study. All wild animals died during treatment after anthropogenic events. After deaths of animals, necropsies were performed and trachea, lungs, large intestine (including stool), and spleen were collected to determine causes of deaths. A high-throughput screening (HTS) quantitative polymerase chain reaction (qPCR) designed to detect 19 pathogens simultaneously against 48 samples in duplicate was performed using nucleic acids extracted from pooled tissues and peripheral blood samples. If positive, singleplex real-time PCR was performed for individual organs or blood samples. RESULTS: The HTS qPCR showed positive results for Campylobacter jejuni (10/121, 8.3%), Campylobacter coli (1/121, 0.8%), Mycoplasma spp. (78/121, 64.5%), and Plasmodium spp. (7/121, 5.7%). Singleplex real-time PCR confirmed that C. jejuni was detected in the large intestine but not in the blood. C. coli was only detected in the large intestine. Mycoplasma spp. were detected in all organs, having the highest proportion in the large intestine and lowest in the blood. Plasmodium spp. was also detected in all organs, with proportions being were similar among organs. CONCLUSIONS: This study shows that wild animals can become carriers of infectious agents without showing any clinical symptoms.

Enhanced primary ciliogenesis via mitochondrial oxidative stress activates AKT to prevent neurotoxicity in HSPA9/mortalin-depleted SH-SY5Y cells.

The primary cilium, an antenna-like structure on the cell surface, acts as a mechanical and chemical sensory organelle. Primary cilia play critical roles in sensing the extracellular environment to coordinate various developmental and homeostatic signaling pathways. Here, we showed that the depletion of heat shock protein family A member 9 (HSPA9)/mortalin stimulates primary ciliogenesis in SH-SY5Y cells. The downregulation of HSPA9 enhances mitochondrial stress by increasing mitochondrial fragmentation and mitochondrial reactive oxygen species (mtROS) generation. Notably, the inhibition of either mtROS production or mitochondrial fission significantly suppressed the increase in primary ciliogenesis in HSPA9-depleted cells. In addition, enhanced primary ciliogenesis contributed to cell survival by activating AKT in SH-SY5Y cells. The abrogation of ciliogenesis through the depletion of IFT88 potentiated neurotoxicity in HSPA9-knockdown cells. Furthermore, both caspase-3 activation and cell death were increased by MK-2206, an AKT inhibitor, in HSPA9-depleted cells. Taken together, our results suggest that enhanced primary ciliogenesis plays an important role in preventing neurotoxicity caused by the loss of HSPA9 in SH-SY5Y cells.

Fluid management in septic patients with pulmonary hypertension, review of the literature.

The management of sepsis in patients with pulmonary hypertension (PH) is challenging due to significant conflicting goals of management and complex hemodynamics. As PH progresses, the ability of right heart to perfuse lungs at a normal central venous pressure (CVP) is impaired. Elevated pulmonary vascular pressure, due to pulmonary vasoconstriction and vascular remodeling, opposes blood flow through lungs thus limiting the ability of right ventricle (RV) to increase cardiac output (CO) and maintain adequate oxygen delivery to tissue. In sepsis without PH, avoidance of volume depletion with intravascular volume replacement, followed by vasopressor therapy if hypoperfusion persists, remains the cornerstone of therapy. Intravenous fluid (IVF) resuscitation based on individualized hemodynamic assessment can help improve the prognosis of critically ill patients. This is accomplished by optimizing CO by maintaining adequate preload, afterload and contractility. Particular challenges in patients with PH include RV failure as a result of pressure and volume overload, gas exchange abnormalities, and managing IVF and diuretic use. Suggested approaches to remedy these difficulties include early recognition of symptoms associated with pressure and volume overload, intravascular volume management strategies and serial lab monitoring to assess electrolytes and renal function.

Comparison of rheological properties between Mixolab-driven dough and bread-making dough under various salt levels.

The properties of wheat dough according to salt level and type of mixer were investigated, and parameters derived from each analysis were comprehensively compared. Mixolab analysis showed that water absorption decreased with salt level while the dough strength increased. In the Mixolab C2 stage, related with thermal strength, C2 temperature and time had stronger correlation with other dough strength parameters than C2 torque. Thickness increase of gluten strand was dominant in the doughs prepared by vertical mixer (VMD) than in those prepared by Mixolab device (MLD), for the same salt level. In large deformation, increase in resistance to extension by salt level was much greater in VMD than in MLD. In small deformation, relationships of salt level with G', G'' and power-law exponent (n) were linear and non-linear in MLD and VMD, respectively. Since MLD could not perfectly reflect VMD, properties of dough should be considered in multiple ways for its comprehensive understanding.

Self-assembly kinetics of short-chain glucan aggregates (SCGA).

Self-assembly (formation and crystallization) kinetics of short-chain glucan aggregates (SCGAs) prepared at isothermal conditions (4, 20, 40, and 60℃) with or without nucleation (4℃, 1 h) were investigated. The fastest formation and crystallization rates of SCGA were observed when short-chain glucan was stored at 4℃ and 20℃, respectively. SCGA was not formed at 60℃. However, nucleation resulted in SCGA forming-ability at 60℃. Moreover, nucleation increased the yield in all temperature conditions. SCGA with nucleation decreased the crystal melting transition temperature range. All SCGAs had nanosized particles (<500 nm) with B-type crystal patterns regardless of temperature and nucleation. Consequently, self-assembly temperature and presence of nucleation step could change the physicochemical characteristics of SCGA, and manipulation of the nucleation step is expected to be an effective method to increase the yield of SCGA and produce SCGA at high temperature.

Recent Synthetic Biology Approaches for Temperature- and Light-Controlled Gene Expression in Bacterial Hosts.

The expression of genes of interest (GOI) can be initiated by providing external stimuli such as temperature shifts and light irradiation. The application of thermal or light stimuli triggers structural changes in stimuli-sensitive biomolecules within the cell, thereby inducing or repressing gene expression. Over the past two decades, several groups have reported genetic circuits that use natural or engineered stimuli-sensitive modules to manipulate gene expression. Here, we summarize versatile strategies of thermosensors and light-driven systems for the conditional expression of GOI in bacterial hosts.

Reliability of the In Silico Prediction Approach to In Vitro Evaluation of Bacterial Toxicity.

Several pathogens that spread through the air are highly contagious, and related infectious diseases are more easily transmitted through airborne transmission under indoor conditions, as observed during the COVID-19 pandemic. Indoor air contaminated by microorganisms, including viruses, bacteria, and fungi, or by derived pathogenic substances, can endanger human health. Thus, identifying and analyzing the potential pathogens residing in the air are crucial to preventing disease and maintaining indoor air quality. Here, we applied deep learning technology to analyze and predict the toxicity of bacteria in indoor air. We trained the ProtBert model on toxic bacterial and virulence factor proteins and applied them to predict the potential toxicity of some bacterial species by analyzing their protein sequences. The results reflect the results of the in vitro analysis of their toxicity in human cells. The in silico-based simulation and the obtained results demonstrated that it is plausible to find possible toxic sequences in unknown protein sequences.

Carnitine Protects against MPP+-Induced Neurotoxicity and Inflammation by Promoting Primary Ciliogenesis in SH-SY5Y Cells.

Primary cilia help to maintain cellular homeostasis by sensing conditions in the extracellular environment, including growth factors, nutrients, and hormones that are involved in various signaling pathways. Recently, we have shown that enhanced primary ciliogenesis in dopamine neurons promotes neuronal survival in a Parkinson's disease model. Moreover, we performed fecal metabolite screening in order to identify several candidates for improving primary ciliogenesis, including L-carnitine and acetyl-L-carnitine. However, the role of carnitine in primary ciliogenesis has remained unclear. In addition, the relationship between primary cilia and neurodegenerative diseases has remained unclear. In this study, we have evaluated the effects of carnitine on primary ciliogenesis in 1-methyl-4-phenylpyridinium ion (MPP+)-treated cells. We found that both L-carnitine and acetyl-L-carnitine promoted primary ciliogenesis in SH-SY5Y cells. In addition, the enhancement of ciliogenesis by carnitine suppressed MPP+-induced mitochondrial reactive oxygen species overproduction and mitochondrial fragmentation in SH-SY5Y cells. Moreover, carnitine inhibited the production of pro-inflammatory cytokines in MPP+-treated SH-SY5Y cells. Taken together, our findings suggest that enhanced ciliogenesis regulates MPP+-induced neurotoxicity and inflammation.

Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation.

Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation.

Infusion of fluorescein into corn and waxy rice starches and its controlled release.

The effects of concentration, temperature, and time on infusion of fluorescein into corn and waxy rice starches and their controlled release pattern were investigated. At low fluorescein concentration (1 µM), temperature significantly affected infusion efficiency. At high fluorescein concentration (50-150 µM), temperature showed little effect; fluorescein concentration significantly affected infusion efficiency. Corn starch showed relatively higher infusion efficiency than waxy rice starch at high concentration. During controlled release, 50% and 81% of infused fluorescein were released from corn and waxy rice starches, respectively, after bacterial α-amylase treatment. However, 61% and 68% of infused fluorescein were released from corn and waxy rice starches, respectively, after pancreatic α-amylase treatment. The dextrose equivalent (DE) value revealed similar patterns, suggesting that degradation of starch by different α-amylases is a major factor affecting release of fluorescein from starch granules. Moreover, granule size of starch greatly affected enzymatic hydrolysis and controlled release in this system. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01059-2.

Impact of chemical modification by immersion with malic acid on the physicochemical properties and resistant starch formation in rice.

The effects of immersion time on the physicochemical properties and resistant starch (RS) formation of malic acid-treated rice were investigated. Malic acid treatment decreased the frequency of cracks within the rice kernel. The color (lightness) was significantly affected by the immersion time, reflecting the browning of rice. The degree of substitution gradually increased with the immersion time and reached a plateau after 12 h, and the intensity of the C=O bond peak detected in the Fourier-transform infrared spectroscopy showed a similar trend. However, the crystallinity of rice decreased as the immersion time increased, which was confirmed by the X-ray diffraction and thermal transition properties. A gradual increase in RS was observed as the immersion time and DS increased, ranging from 44.5% to 73.3%, reaching a maximum after 12 h of immersion. Therefore, 12 h was determined to be the optimal immersion time for maximizing RS content. This information about the structural characteristics and heat-stable properties of malic acid-treated rice in starch digestion can be used to develop a low-digestible food ingredient and lead to further application of the study. PRACTICAL APPLICATION: This study reported the preparation and physicochemical properties of malic acid-treated resistant starch with different immersion times. This information could contribute to the structural characterization of resistant starch and the development of low-calorie processed rice products.

Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells.

Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells.

High-flow nasal cannula application in an infant patient with laryngomalacia during general anesthesia: A case report.

RATIONALE: Laryngomalacia is defined as the collapse of supraglottic structures and can cause not only strider but also trigger difficulties with ventilation and endotracheal intubation during anesthesia management. High-flow nasal cannula (HFNC) has been used to manage patients at high risk of hypoxemia in the intensive care unit; however, limited literature information is available for the application of HFNC to infant patients with laryngomalacia during anesthesia practice. PATIENT CONCERNS: A 2-month-old male infant was scheduled to undergo surgery for inguinal hernia and undescended testis with general anesthesia. DIAGNOSIS: The patient had subcostal retraction while breathing and frequent oxygen desaturation events and was diagnosed laryngomalacia. INTERVENTIONS: After the patient was supplied oxygen via HFNC and then given general anesthesia, the initial 2 attempts of endotracheal intubation with a rigid laryngoscope were unsuccessful because the vocal cords were obscured by the epiglottis. A third intubation attempt was performed and successful with a 3.0-sized, uncuffed endotracheal tube within 20 minutes of the initial attempt. OUTCOMES: No airway complications emerged and oxygen saturation remained at greater than 98% during general anesthesia. The patient was discharged 5 days after surgery without any adverse side effects. LESSONS: Continuous oxygenation via HFNC is a good choice to prevent desaturation during difficult tracheal intubations in infant patients with laryngomalacia. This device is expected to be useful for intubation not only in patients with laryngomalacia, but also in infant patients with a predicted high risk of oxygen desaturation events during general anesthesia.

Infusion efficiency of fluorescein derivatives of different molecular sizes into various starches under atmospheric and high hydrostatic pressures.

Fluorescein isothiocyanate-dextrans (FDs) of different molecular weights were infused into corn, waxy rice, tapioca, and potato starches under atmospheric and high hydrostatic pressures (HHP). FD4, FD10, FD20, and FD40 (Mw 4000, 10,000, 20,000, and 40,000, respectively) were used as infusion materials. Confocal laser scanning microscopy confirmed that all FDs except FD40 infused into corn, waxy rice, and tapioca starches. However, no FDs infused into potato starch. Corn starch had the highest amounts of infused FDs. As molar mass increased, the amount of infused FD decreased in all starches. The infused amounts of FDs in corn starch were similar at 200-300 MPa and atmospheric pressure. Infusion of FDs at 400 MPa was reduced due to partial gelatinization. These results confirm that infusion efficiency is inversely proportional to the molecular weight of the infused material and large materials (Mw > 40,000) cannot be infused into starch granules under atmospheric pressure or HHP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00972-2.

Instrumental and Sensory Characteristics of Commercial Korean Rice Noodles.

In this study, the rheological properties of several commercial rice noodle strands were investigated. In the bending test, failure stress decreased as the cooking temperature increased from 80 to 90 °C, and the cooking time increased from 3 to 4 min for higher rice content noodles (>60%). The stress-relaxation test and sensory tests were carried out with bundles of noodles to investigate correlations with the bending test. The modulus of elasticity was higher at 80 than 90 °C. However, no correlation was found between cooking temperature and the rheological properties of lower rice content noodles. In the stress relaxation test, the deviation was larger due to the empty space in the bundle. In the correlation analysis, sensory stickiness was correlated with a modulus of elasticity in the bending test. Comparing the bending and stress-relaxation tests, each instrumental variable showed differences in the rheological properties of rice noodles in strands and bundles. However, the bending test measured with noodle strands seemed to be most suitable as a method of measuring the rheological properties of rice noodles.

Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model.

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.