Comparison of the pharmacokinetic characteristics and bioequivalence between two nanosuspension formulations of megestrol acetate in healthy Korean male subjects.

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence. Trial Registration: ClinicalTrials.gov Identifier: NCT06147908.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

Distributions of PCDD/Fs, PCBs, and PCNs in coastal sediments collected from major industrial bays in South Korea.

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) were assessed in coastal sediments from industrial bays in South Korea to evaluate the pollution levels and their environmental impact. The mean sediment concentrations of Σ17 PCDD/Fs, Σ18 PCBs, and Σ15 PCNs were 198 ± 140, 3427 ± 7037, and 85 ± 336 pg/g dw, respectively. Generally, pollutant concentrations in the inner bay were higher than those in the outer bay, indicating the influence of industrial emissions and harbor activities. The primary sources were identified as steel manufacturing and wastewater treatment plants for PCDD/Fs, harbor and shipbuilding activities for PCBs, and combustion-related sources for PCNs. Notably, PCDD/F concentrations exceeded sediment guideline values. The combined effects of PCDD/Fs and PCBs demonstrated adverse impacts on aquatic organisms. Hence, the release of toxic pollutants into the marine environment could have potential biological effects due to the combined impact of these various compounds.

Comparison of postoperative pain between transoral and conventional thyroidectomy: a propensity score-matched analysis.

BACKGROUND: The extent of postoperative pain following transoral thyroidectomy is not well-understood and remains a subject of debate. This study aims to analyze and compare postoperative pain levels between patients undergoing transoral and conventional transcervical thyroidectomy. METHODS: A prospective evaluation on postoperative pain was conducted in 310 patients undergoing conventional thyroidectomy and 194 undergoing transoral thyroidectomy. Pain levels were evaluated using the numerical rating scale (NRS, ranging from 0 to 10) through preoperative and postoperative questionnaires at specified time points: 1, 3, and 6 days, and 1 and 3 months following surgery. Propensity score-matched analysis was carried out based on six covariates: sex, age, body mass index, extent of thyroidectomy, tumor size, and central neck dissection. RESULTS: After propensity score matching based on the six covariates, 121 patient pairs were identified from each group. Within this matched cohort, postoperative pain scores significantly worsened 1 day after surgery but showed progressive recovery up to 3 months post-surgery in both groups. The transoral group exhibited higher postoperative pain scores than the conventional group from day 1 (4.43 ± 2.6 vs. 3.11 ± 2.5, p < 0.001) to day 6 (1.76 ± 1.9 vs. 1.13 ± 1.6, p = 0.016) post-surgery, with no significant difference noted at 1 month. Among transoral procedures, pain scores were significantly higher for the endoscopic approach compared to the robotic approach on days 1 (5.52 ± 2.3 vs. 4.29 ± 2.3, p = 0.028) and 3 (3.52 ± 2.5 vs. 2.64 ± 2.0, p = 0.047) post-surgery. CONCLUSIONS: Postoperative pain was significantly higher in transoral thyroidectomy compared to conventional thyroidectomy up to 6 days post-surgery. Within the transoral group, the robotic procedure resulted in lower pain levels than the endoscopic approach during the early postoperative period.

Ecoinformatic Analysis of the Gut Ecological Diversity of Wild and Captive Long-Tailed Gorals Using Improved ITS2 Region Primers to Support Their Conservation.

Ex situ conservation is used to protect endangered wildlife. As captive and wild long-tailed gorals are known to be similar, individuals under ex situ conservation can be reintroduced into nature. However, there is no appropriate indicator to evaluate them. Here, we amplified the internal transcribed spacer 2 (ITS2) region and compared the gut ecological information (eco-information) of captive and wild long-tailed gorals. We validated the existing ITS86F and ITS4 universal primers using reference sequences of the National Center for Biotechnology Information (NCBI) and improved their matching rates. We compared the gut eco-information of captive and wild long-tailed gorals obtained through experiments using the improved primer pair and found that the gut ecological diversity of captive gorals was low. Based on this, we suggested that the gut eco-information can be used as an evaluation index before reintroducing captive long-tailed gorals. Furthermore, we identified four plant types from the gut eco-information of wild long-tailed gorals, which can be the additional food sources to enhance the reduced intestinal ecological diversity of the captive animals.

Comparison of the acid suppression effects between low-dose esomeprazole and famotidine in healthy subjects.

OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.

Consensus Definition of Blood Samples from the Subcategorized Normal Controls in the Korea Biobank Network.

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies.

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study.

BACKGROUND: CT-P47 is a candidate tocilizumab biosimilar. This study assessed the pharmacokinetic (PK) equivalence of CT-P47 and European Union-approved reference tocilizumab (EU-tocilizumab) in healthy Asian adults. RESEARCH DESIGN AND METHODS: This double-blind, multicenter, parallel-group trial randomized healthy adults (1:1) to receive a single (162 mg/0.9 mL) subcutaneous dose of CT-P47 or EU-tocilizumab. The primary endpoint (Part 2) was PK equivalence by area under the concentration - time curve (AUC) from time zero to last quantifiable concentration (AUC0-last), AUC from time zero to infinity (AUC0-inf), and maximum serum concentration (Cmax). PK equivalence was concluded if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the 80-125% equivalence margin. Additional PK endpoints, immunogenicity, and safety were evaluated. RESULTS: In Part 2, 289 participants were randomized (146 CT-P47; 143 EU-tocilizumab); 284 received study drug. AUC0-last, AUC0-inf, and Cmax were equivalent between CT-P47 and EU-tocilizumab: 90% CIs for the ratios of gLSMs were within the 80-125% equivalence margin. Secondary PK endpoints, immunogenicity, and safety were comparable between groups. CONCLUSIONS: CT-P47 demonstrated PK equivalence with EU-tocilizumab and was well tolerated, following a single dose in healthy adults. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05188378.

Tocilizumab is a biologic medicine used to treat inflammatory diseases including rheumatoid arthritis. Biosimilars are drugs that are highly similar to an already approved, 'reference' biologic medicine. This means that they do not have any differences from the reference product in factors including structure, biologic function, efficacy, and safety, that might affect how well they work in patients. Biosimilars are often available at a lower cost than reference drugs, so their use can provide patients with better access to expensive treatments. There are no approved biosimilars of tocilizumab so far: CT-P47 is currently in development as a potential tocilizumab biosimilar.In the main part of this study, 289 healthy Asian volunteers were randomly allocated to receive a single injection of either CT-P47 or the reference drug, European Union-approved tocilizumab (EU-tocilizumab). The main aim of the study was to find out whether CT-P47 and EU-tocilizumab were equivalent in terms of pharmacokinetics (drug absorption, distribution, metabolism, and excretion by the body). This is part of a standard process required by regulatory authorities to ensure that biosimilars work as well as their reference drugs. Analysis of blood samples taken over 43 days showed that the pharmacokinetic profiles of CT-P47 and EU-tocilizumab were equivalent, after the volunteers received a single dose of either drug. Safety and immunogenicity (immune responses made to the drug) were also comparable between CT-P47 and EU-tocilizumab. While only healthy Asian adults were included, further research comparing CT-P47 with reference tocilizumab will help to ensure that the findings from the study can be applied to broader populations.

Pathophysiological Roles of Transient Receptor Potential (Trp) Channels and Zinc Toxicity in Brain Disease.

Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels. Brain disease, especially ischemic stroke, epilepsy, and traumatic brain injury, triggers the dysregulation of ionic gradients and promotes the excessive release of neuro-transmitters and zinc. The divalent metal cation zinc is highly distributed in the brain and is specifically located in the pre-synaptic vesicles as free ions, usually existing in cytoplasm bound with metallothionein. Although adequate zinc is essential for regulating diverse physiological functions, the brain-disease-induced excessive release and translocation of zinc causes cell damage, including oxidative stress, apoptotic cascades, and disturbances in energy metabolism. Therefore, the regulation of zinc homeostasis following brain disease is critical for the prevention of brain damage. In this review, we summarize recent experimental research findings regarding how TRP channels (mainly TRPC and TRPM) and zinc are regulated in animal brain-disease models of global cerebral ischemia, epilepsy, and traumatic brain injury. The blockade of zinc translocation via the inhibition of TRPC and TRPM channels using known channel antagonists, was shown to be neuroprotective in brain disease. The regulation of both zinc and TRP channels may serve as targets for treating and preventing neuronal death.

Pharmacokinetic and Pharmacodynamic Characteristics of Pelubiprofen Tromethamine vs. Pelubiprofen in Healthy Subjects.

Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.

Nationwide assessment of atmospheric organochlorine pesticides over a decade during 2008-2017 in South Korea.

Long-term nationwide atmospheric monitoring of organochlorine pesticides (OCPs) was performed in South Korea during 2008-2017. Their occurrences, seasonal and temporal variability, sources, and effect of ambient temperature were investigated. The OCPs are pronounced with a mean concentration of total OCPs ranging from 5.2 to 256 pg/Sm3. However, a decrease of 54 % was observed in the mean concentration of total OCPs from 2008 to 2017 associated with regulatory actions. OCP concentrations did not show any variations between the different site types, and OCPs were ubiquitously present at all site types. The mean concentration of total OCPs in summer was two-fold higher than in winter. The concentrations of DRINs, DDTs, ENDOs, and HCHs were significantly higher in summer, but the concentrations of chlordane and heptachlor were higher in winter. The diagnostic ratios identified major sources as ongoing sources, past use, and atmospheric transport. Clausius Clapeyron plots strongly suggested the re-emission of α-endosulfan, ß-endosulfan, α-HCH, and ß-HCH, and ΔHsa (enthalpy of surface air exchange) values suggested the influence of the transport and/or new sources on aldrin, dieldrin, and chlordane. The occurrence of OCPs due to re-emissions, ongoing sources, and long-range atmospheric transport could be a challenge towards the complete phase-out of OCPs in South Korea.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-CreERT2; PKM2f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.

The Protective Role of Glutathione on Zinc-Induced Neuron Death after Brain Injuries.

Glutathione (GSH) is necessary for maintaining physiological antioxidant function, which is responsible for maintaining free radicals derived from reactive oxygen species at low levels and is associated with improved cognitive performance after brain injury. GSH is produced by the linkage of tripeptides that consist of glutamic acid, cysteine, and glycine. The adequate supplementation of GSH has neuroprotective effects in several brain injuries such as cerebral ischemia, hypoglycemia, and traumatic brain injury. Brain injuries produce an excess of reactive oxygen species through complex biochemical cascades, which exacerbates primary neuronal damage. GSH concentrations are known to be closely correlated with the activities of certain genes such as excitatory amino acid carrier 1 (EAAC1), glutamate transporter-associated protein 3-18 (Gtrap3-18), and zinc transporter 3 (ZnT3). Following brain-injury-induced oxidative stress, EAAC1 function is negatively impacted, which then reduces cysteine absorption and impairs neuronal GSH synthesis. In these circumstances, vesicular zinc is also released into the synaptic cleft and then translocated into postsynaptic neurons. The excessive influx of zinc inhibits glutathione reductase, which inhibits GSH's antioxidant functions in neurons, resulting in neuronal damage and ultimately in the impairment of cognitive function. Therefore, in this review, we explore the overall relationship between zinc and GSH in terms of oxidative stress and neuronal cell death. Furthermore, we seek to understand how the modulation of zinc can rescue brain-insult-induced neuronal death after ischemia, hypoglycemia, and traumatic brain injury.

Acid Sphingomyelinase Inhibitor, Imipramine, Reduces Hippocampal Neuronal Death after Traumatic Brain Injury.

Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells. Under normal conditions, ceramide plays an important role in various physiological functions, such as differentiation and apoptosis. However, under pathological conditions, excessive ceramide production is toxic and activates the neuronal-death pathway. Therefore, we hypothesized that the inhibition of ASMase activity by imipramine would reduce ceramide formation and thus prevent TBI-induced neuronal death. To test our hypothesis, an ASMase inhibitor, imipramine (10 mg/kg, i.p.), was administrated to rats immediately after TBI. Based on the results of this study, we confirmed that imipramine significantly reduced ceramide formation, dendritic loss, oxidative stress, and neuronal death in the TBI-imipramine group compared with the TBI-vehicle group. Additionally, we validated that imipramine prevented TBI-induced cognitive dysfunction and the modified neurological severity score. Consequently, we suggest that ASMase inhibition may be a promising therapeutic strategy to reduce hippocampal neuronal death after TBI.

Changes in Microbial Community Structure in Response to Gummosis in Peach Tree Bark.

Peach gummosis disease has been identified as a serious challenge in Korean agriculture and has developed to become a major cause of agricultural productivity losses. However, treatments for gummosis have not been systemically established and studies of the microbiome closely related to this plant disease are lacking. Therefore, we analyzed the bacterial and fungal communities in the bark and rhizosphere soil of healthy peach trees and those with gummosis. Through high-throughput sequencing, we obtained unprecedented insights into the bacterial and fungal dynamics of each group, including their diversity and taxonomic classification, as well as network analyses. We found that the presence of gummosis drives a significantly higher alpha diversity in the bark bacterial community. Peach gummosis bark mycobiomes included greater numbers of opportunistic pathogens such as Ascochyta, Botryosphaeria, Saccharomyces, Nectriaceae_NA, Trametes, and Valsaceae_NA. However, the microbiome also included bacteria beneficial to plant growth and the production of polysaccharides-namely, 1174-901-12, Catenibacterium, Cutibacterium, Friedmanniella, Methylobacterium-Methylorubrum, Pseudomonas, Rhodobacter, and Sphingomonas. Furthermore, we confirmed that gummosis induced a more complex structure in the bark microbiome network. We conclude that the findings of this study provide a valuable aid in profiling the overall peach tree microbial ecosystem, which can be utilized to develop precise biomarkers for the early diagnosis of gummosis.

Combined Treatment of Dichloroacetic Acid and Pyruvate Increased Neuronal Survival after Seizure.

During seizure activity, glucose and Adenosine triphosphate (ATP) levels are significantly decreased in the brain, which is a contributing factor to seizure-induced neuronal death. Dichloroacetic acid (DCA) has been shown to prevent cell death. DCA is also known to be involved in adenosine triphosphate (ATP) production by activating pyruvate dehydrogenase (PDH), a gatekeeper of glucose oxidation, as a pyruvate dehydrogenase kinase (PDK) inhibitor. To confirm these findings, in this study, rats were given a per oral (P.O.) injection of DCA (100 mg/kg) with pyruvate (50 mg/kg) once per day for 1 week starting 2 h after the onset of seizures induced by pilocarpine administration. Neuronal death and oxidative stress were assessed 1 week after seizure to determine if the combined treatment of pyruvate and DCA increased neuronal survival and reduced oxidative damage in the hippocampus. We found that the combined treatment of pyruvate and DCA showed protective effects against seizure-associated hippocampal neuronal cell death compared to the vehicle-treated group. Treatment with combined pyruvate and DCA after seizure may have a therapeutic effect by increasing the proportion of pyruvate converted to ATP. Thus, the current research demonstrates that the combined treatment of pyruvate and DCA may have therapeutic potential in seizure-induced neuronal death.

Review of the Current State of Freely Accessible Web Tools for the Analysis of 16S rRNA Sequencing of the Gut Microbiome.

Owing to the emergence and improvement of high-throughput technology and the associated reduction in costs, next-generation sequencing (NGS) technology has made large-scale sampling and sequencing possible. With the large volume of data produced, the processing and downstream analysis of data are important for ensuring meaningful results and interpretation. Problems in data analysis may be encountered if researchers have little experience in using programming languages, especially if they are clinicians and beginners in the field. A strategy for solving this problem involves ensuring easy access to commercial software and tools. Here, we observed the current status of free web-based tools for microbiome analysis that can help users analyze and handle microbiome data effortlessly. We limited our search to freely available web-based tools and identified MicrobiomeAnalyst, Mian, gcMeta, VAMPS, and Microbiome Toolbox. We also highlighted the various analyses that each web tool offers, how users can analyze their data using each web tool, and noted some of their limitations. From the abovementioned list, gcMeta, VAMPS, and Microbiome Toolbox had several issues that made the analysis more difficult. Over time, as more data are generated and accessed, more users will analyze microbiome data. Thus, the availability of free and easily accessible web tools can enable the easy use and analysis of microbiome data, especially for those users with less experience in using command-line interfaces.

Assessment of organochlorine pesticides in the atmosphere of South Korea: spatial distribution, seasonal variation, and sources.

Organochlorine pesticides (OCPs) are widely used in certain countries. We determined atmospheric concentrations, distribution patterns, and seasonal variations of OCPs at four sites in South Korea for 1 year. Samples of 22 OCPs were collected using a high-volume air sampler, and measured via the isotope dilution method with HRGC/HRMS. In South Korea, pentachlorobenzene (PeCB), hexachlorocyclohexane (HCB), and endosulfan (EnSF) were dominant, accounting for > 87% of total OCPs. Spatial distributions showed significant differences and the highest levels were observed in Seosan (295.2 pg·m-3), indicating the compounding potential of diverse sources as Seosan has concentrated large-scale industrial complexes and agricultural activity (Seoul: 243.6 pg·m-3 > Jeju: 193.5 pg·m-3 > Baengnyeong: 178.2 pg·m-3). The isomeric ratios of OCPs in the South Korean atmosphere indicated that the dominant sources of HCB and dichlorodiphenyltrichloroethane were primarily used in the past; meanwhile, chlordane (CHL) and EnSFs were derived from recent material inputs. Seasonally, OCP concentrations largely peaked in summer with minimum values in winter. This apparent temperature dependence suggests the re-volatilization of accumulated chemicals into the atmosphere. Additionally, an air mass back trajectory indicated the influence of pollutants released from a reservoir through long-range atmospheric transport in the summer. In particular, restricted OCPs are primarily released into the atmosphere by inadvertent sources, such as industrial activities and volatilization from contaminated areas. Thus, severe OCP pollution in Korea is due to the mobile nature of the particles. These data can be useful for the continuous monitoring of long-range transported air pollutants that are transferred between countries.

Organochlorine pesticides in the urban, suburban, agricultural, and industrial soil in South Korea after three decades of ban: Spatial distribution, sources, time trend, and implicated risks.

Organochlorine pesticides in soil samples across urban, suburban, agricultural, and industrial sites were analyzed every year between 2013 and 2016 in South Korea. The study aims to understand the residual status, diminution of occurrence from the South Korean environment, and its risk to humans after three decades of the ban. A general decreasing trend of OCPs has been observed over the years. The OCP concentrations were below the guideline values prescribed for soil pollution. Metabolites like p,p'-DDD and endosulfan sulfate contributed a major portion to the total OCP concentration over the years. The agricultural sites showed higher OCP levels than other site types. Compositional profile and diagnostic ratios suggested that the occurrence of DDT and endosulfan residues were due to historical inputs, but those of HCH and chlordane reflect recent usage in some pockets. The calculated incremental lifetime cancer risk was within the safety limit for all age groups across the genders in the majority of the sites. It is evident that the OCP load on soil is decreasing since the ban on usage. However, regular monitoring with a special focus on metabolites can be an effective control measure to regulate and eliminate the contamination of OCPs.