Isolation of New Diterpenoids from the Halophyte, Vitex rotundifolia, and their Antioxidant and Anti-inflammatory Activities.

In this study, three diterpenoids (1-3), including one known compound (1), were isolated from the fruits of Vitex rotundifolia and their structures were determined via spectroscopic analysis. In lipopolysaccharide-stimulated RAW264.7 cells, these compounds dose-dependently decreased the intracellular reactive oxygen species levels and nitric oxide production compared to those in the control cells. At 25 µM/mL, these compounds also diminished the protein expression of the pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6, with compound 3 exhibiting the most potent inhibitory effect.

The Epidemiological and Clinical Characteristics of the Largest Outbreak of Enterohemorrhagic Escherichia coli in Korea.

BACKGROUND: The largest outbreak of enterohemorrhagic Escherichia coli (EHEC) O157:H7 occurred at a preschool in South Korea from June 12 to 29, 2020. This study aimed to analyze the epidemiological and clinical characteristics of EHEC infection in this outbreak. METHODS: Epidemiological investigation was performed on all 184 children and 19 workers at the preschool using a standard questionnaire to assess symptoms, food intake, attendance, and special activity history. Pulsed-field gel electrophoresis analysis of confirmed cases was performed to determine genetic relevance. RESULTS: During this outbreak, 103 children were affected, whereas only one infection was identified in adults. Of the 103 pediatric patients, 85 had symptoms (82.5%), including diarrhea, abdominal pain, bloody stool, fever, and vomiting. Thirty-two patients (31.1%) were hospitalized, 15 (14.6%) were diagnosed with hemolytic uremic syndrome, and 4 (3.9%) received dialysis treatment. Pulsed-field gel electrophoresis analysis identified 4 genotypes with high genetic relevance (92.3%). Epidemiological investigation revealed that this outbreak might have occurred from ingesting foods stored in a refrigerator with a constant temperature above 10°C, which was conducive to bacterial growth. Despite several measures after outbreak recognition, new infections continued to appear. Therefore, the preschool was forced to close on June 19 to prevent further person-to-person transmission. CONCLUSION: Our findings from the response to the largest outbreak will help prepare countermeasures against future EHEC outbreak.

Serial Intervals and Household Transmission of SARS-CoV-2 Omicron Variant, South Korea, 2021.

To clarify transmissibility of the severe acute respiratory syndrome coronavirus 2 Omicron variant, we determined serial intervals and secondary attack rates among household contacts in South Korea. Mean serial interval for 12 transmission pairs was 2.9 days, and secondary attack rate among 25 households was 50.0%, raising concern about a rapid surge in cases.

Time from Exposure to Diagnosis among Quarantined Close Contacts of SARS-CoV-2 Omicron Variant Index Case-Patients, South Korea.

To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Glucosinolate Profiling and Expression Analysis of Glucosinolate Biosynthesis Genes Differentiate White Mold Resistant and Susceptible Cabbage Lines.

Sclerotinia stem rot (white mold), caused by the fungus Sclerotinia sclerotiorum, is a serious disease of Brassica crops worldwide. Despite considerable progress in investigating plant defense mechanisms against this pathogen, which have revealed the involvement of glucosinolates, the host⁻pathogen interaction between cabbage (Brassica oleracea) and S. sclerotiorum has not been fully explored. Here, we investigated glucosinolate profiles and the expression of glucosinolate biosynthesis genes in white-mold-resistant (R) and -susceptible (S) lines of cabbage after infection with S. sclerotiorum. The simultaneous rise in the levels of the aliphatic glucosinate glucoiberverin (GIV) and the indolic glucosinate glucobrassicin (GBS) was linked to white mold resistance in cabbage. Principal component analysis showed close association between fungal treatment and cabbage GIV and GBS contents. The correlation analysis showed significant positive associations between GIV content and expression of the glucosinolate biosynthesis genes ST5b-Bol026202 and ST5c-Bol030757, and between GBS content and the expression of the glucosinolate biosynthesis genes ST5a-Bol026200 and ST5a-Bol039395. Our results revealed that S. sclerotiorum infection of cabbage induces the expression of glucosinolate biosynthesis genes, altering the content of individual glucosinolates. This relationship between the expression of glucosinolate biosynthesis genes and accumulation of the corresponding glucosinolates and resistance to white mold extends the molecular understanding of glucosinolate-negotiated defense against S. sclerotiorum in cabbage.

Galangin enhances TGF-ß1-mediated growth inhibition by suppressing phosphorylation of threonine 179 residue in Smad3 linker region.

Smad3 linker phosphorylation is a candidate target for several kinases that play important roles in cancer cell initiation, proliferation and progression. Also, Smad3 is an essential intracellular mediator of TGF-ß1-induced transcriptional responses during carcinogenesis. Therefore, it is highly advantageous to identify and develop inhibitors targeting Smad3 linker phosphorylation for the treatment of cancers. Galangin (3,5,7-trihydroxyflavone) has been known to be an active flavonoid showing a cytotoxic effect on several cancer cells. However, the mechanism of action of galangin in various cancers remains unclear, and there has been no report concerning regulation of Smad3 phosphorylation by galangin. In the present study, we show that galangin significantly induced apoptosis and inhibited cell proliferation in the presence of TGF-ß1 in both human prostate and pancreatic cancer cell lines. Particularly, galangin effectively inhibits phosphorylation of the Thr-179 site at Smad3 linker region through suppression of CDK4 phosphorylation. Thus, galangin can be a promising candidate as a selective inhibitor to suppress phosphorylation of Smad3 linker region.

Ethnopharmacological uses, phytochemistry, biological activities, and biotechnological applications of Eclipta prostrata.

Eclipta prostrata belongs to a family of medicinal plants (Asteraceae) and plays a role in the treatment of several diseases, including infectious hepatitis, snake venom poisoning, gastritis, and respiratory diseases such as a cough and asthma. A number of compounds, including thiophene derivatives, steroids, triterpenes, flavonoids, polyacetylenes, polypeptides, and coumestans, have been isolated from E. prostrata. The plant functional compounds can act as reducing agent in the field of nanoparticle synthesis. The extracts of E. prostrata are widely used for green biosynthesis of various metal and metal oxide nanoparticles, nanoparticles, which showed a potential for pharmaceutical, biotechnological, and biomedical applications. Establishment of a efficient in vitro regeneration and genetic transformation method of E. prostrata is a vital prerequisite for application of biotechnology in order to improve secondary metabolite yields. The present mini-review discusses its pharmacological profile, chemical constituents, biotechnological, and ethnomedical uses, mainly focusing on antimyotoxic, antihemorrhagic, antiproliferative, antioxidant, antitumor, antihyperglycemic, antidementia, antimicrobial, antihyperlipidemic, antivenom, anti-HIV, and larvicidal activities, so that the pharmaceutical potential of the plant can be better evaluated. The mini review, providing up-to-date phytochemical and other information on E. prostrata, will serve a reference for further studies.

Prevalence and Characteristics of Tuberculosis in the Korean Homeless Population Based on Nationwide Tuberculosis Screening.

Background: The government of Korea implemented a strategy of prevention and early diagnosis in high-risk groups to reduce the tuberculosis (TB) burden. This study aims to investigate the TB epidemiology and gap in understanding of TB prevalence among homeless individuals by analyzing active TB chest X-ray (CXR) screening results in Korea. Methods: The Korean National Tuberculosis Association conducted active TB screening with CXR for homeless groups from January 1 to December 31, 2021. Sputum acid fast bacilli smear and culture were performed for the subjects suggestive of TB on CXR. We performed a cross-sectional analysis of the data in comparison with the national health screening results from the general population. Results: Among 17,713 homeless persons, 40 (0.23%), 3,077 (17.37%), and 79 (0.45%) were categorized as suggested TB, inactive TB, and observation required, respectively. Prevalence of suggested TB in the homeless was significantly higher (3-5 fold) than in the national general health screening based on age category (p < 0.005). Twenty-nine cases were confirmed as TB, yielding a prevalence of 164 cases per 100,000 individuals; 19 of these 29 cases showed inactive TB on CXR. Body mass index (p = 0.0478) and CXR result (p < 0.001) significantly correlated with confirmed TB based on multivariable analysis. Conclusion: Nutrition status and CXR results, especially that of inactive TB, should be considered in active TB screening of the homeless population, where TB prevalence is higher than the general population.

Tm4sf19 deficiency inhibits osteoclast multinucleation and prevents bone loss.

BACKGROUND: Multinucleation is a hallmark of osteoclast formation and has a unique ability to resorb bone matrix. During osteoclast differentiation, the cytoskeleton reorganization results in the generation of actin belts and eventual bone resorption. Tetraspanins are involved in adhesion, migration and fusion in various cells. However, its function in osteoclast is still unclear. In this study, we identified Tm4sf19, a member of the tetraspanin family, as a regulator of osteoclast function. MATERIALS AND METHODS: We investigate the effect of Tm4sf19 deficiency on osteoclast differentiation using bone marrow-derived macrophages obtained from wild type (WT), Tm4sf19 knockout (KO) and Tm4sf19 LELΔ mice lacking the large extracellular loop (LEL). We analyzed bone mass of young and aged WT, KO and LELΔ mice by µCT analysis. The effects of Tm4sf19 LEL-Fc fusion protein were accessed in osteoclast differentiation and osteoporosis animal model. RESULTS: We found that deficiency of Tm4sf19 inhibited osteoclast function and LEL of Tm4sf19 was responsible for its function in osteoclasts in vitro. KO and LELΔ mice exhibited higher trabecular bone mass compared to WT mice. We found that Tm4sf19 interacts with integrin αvß3 through LEL, and that this binding is important for cytoskeletal rearrangements in osteoclast by regulating signaling downstream of integrin αvß3. Treatment with LEL-Fc fusion protein inhibited osteoclast function in vitro and administration of LEL-Fc prevented bone loss in an osteoporosis mouse model in vivo. CONCLUSION: We suggest that Tm4sf19 regulates osteoclast function and that LEL-Fc may be a promising drug to target bone destructive diseases caused by osteoclast hyper-differentiation.

Cu(I)-thioether coordination complexes based on a chiral cyclic ß-amino acid ligand.

Coordination complexes, particularly metalloproteins, highlight the significance of metal-sulfur bonds in biological processes. Their unique attributes inspire efforts to synthetically reproduce these intricate metal-sulfur motifs. Here, we investigate the synthesis and characterization of copper(I)-thioether coordination complexes derived from copper(I) halides and the chiral cyclic ß-amino acid trans-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), which present distinctive structural properties and ligand-to-metal ratios. By incorporating ATTC as the ligand, we generated complexes that feature a unique chiral conformation and the capacity for hydrogen bonding, facilitating the formation of distinct geometric structures. Through spectroscopic analyses and density functional theory (DFT) calculations, we studied the complexes' optical properties, including their emission bands and variable second-harmonic generation (SHG) efficiencies, which vary based on the halide used. Our findings underscore the potential of the ATTC ligand in creating unusual coordination complexes and pave the way for further investigations into their potential applications, particularly within materials science.

Liver-Derived Exosomes Induce Inflammation and Lipogenesis in Mice Fed High-Energy Diets.

The liver is an endocrine organ and is the first organ exposed to nutrients when they are absorbed into the body before being metabolized by the distal organs. Although the liver plays an essential role in the interactions between the metabolic organs, their regulatory mechanisms have not been elucidated. Exosomes mediate communication between cells and primarily enable the transport of lipids, mRNAs, miRNAs, and proteins between cells. In this study, we investigated the effects of lipid metabolism on the liver and adipose tissue between mice fed high-fat (HF) and high-fat/sucrose (HFS) diets and determined the effects of liver tissue-derived exosomes on adipocytes to understand the underlying mechanisms associated with obesity-related metabolic diseases. Normal, HF, and HFS diets were fed to the mice for 12 weeks to compare differences based on dietary patterns. We showed different lipid metabolism effects on the liver and adipose tissue between HF- and HFS-fed mice. In the liver, fibrosis, inflammation, and lipogenesis were activated at higher levels in the HFS than in the HF group, and lipolysis was activated at higher levels in the HF than in the HFS group. In adipose tissue, adipogenesis, fatty acid transport, and lipolysis were activated at higher levels in the HF than in the HFS group, and inflammation and lipogenesis were activated at higher levels in the HFS than in the HF group. This result followed a similar trend reported in 3T3-L1 cells treated with liver-derived exosomes. In addition, the TG content of the liver-derived exosomes was significantly higher, and lipid accumulation was accelerated in the HFS than in the HF group. Based on these results, continuous exposure to HF and HFS diets induces lipid accumulation mediated by liver-derived exosomes; however, there is a difference in lipid metabolism. These results contribute to the elucidation of the mechanisms of exosome function in relation to obesity-related metabolic diseases and the metabolic relationship between tissues.

A high-performance liquid chromatography-evaporative light scattering detection-based quantitative analytical method for polyvinyl alcohol in food supplements with pyrolysis-gas chromatography/mass spectrometry-based verification.

Polyvinyl alcohol (PVOH) is extensively used in agricultural, pharmaceutical, textile, and food industries. A new high-performance liquid chromatography (HPLC) method with evaporative light scattering detection (ELSD) was developed for the quantitative analysis of PVOH products. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was employed for method verification. The HPLC-ELSD method exhibited acceptable linearity (R2 > 0.99), with limits of detection and quantitation of 19.43 and 58.88 µg/mL, respectively. Accuracies of 91.16-102.30% were estimated based on recoveries of the intra- and inter-day tests of PVOH. Repeatability and intermediate precision (%RSD) of 1.23-4.45 and 2.18-6.95, respectively, were obtained. The presence of PVOH in the HPLC peaks was further verified using typical indicators of PVOH in Py-GC/MS analysis, such as acetaldehyde, 2,5-dihydrofuran, benzaldehyde, and crotonaldehyde. This novel HPLC method with Py-GC/MS-based verification can be successfully applied for analyzing PVOH in dietary supplement tablets.

Degradation of DRAK1 by CUL3/SPOP E3 Ubiquitin ligase promotes tumor growth of paclitaxel-resistant cervical cancer cells.

Despite favorable responses to initial chemotherapy, drug resistance is a major cause limiting chemotherapeutic efficacy in many advanced cancers. However, mechanisms that drive drug-specific resistance in chemotherapy for patients with advanced cancers are still unclear. Here, we report a unique role of death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK1) associated with paclitaxel resistance in cervical cancer cells. Interestingly, DRAK1 protein level was markedly decreased in paclitaxel-resistant cervical cancer cells without affecting its mRNA expression, which resulted in an increase in tumor necrosis factor receptor-associated factor 6 (TRAF6) expression, as well as an activation of TRAF6-mediated nuclear factor-kappa B (NF-κB) signaling cascade, thereby promoting tumor progression. DRAK1 depletion markedly increased the chemotherapeutic IC50 values of paclitaxel in cervical cancer cells. Ectopic expression of DRAK1 inhibited growth of paclitaxel-resistant cervical cancer cells in vitro and in vivo. Furthermore, DRAK1 was markedly underexpressed in chemoresistant cervical cancer patient tissues compared with chemosensitive samples. We found that DRAK1 protein was destabilized through K48-linked polyubiquitination promoted by the Cullin scaffold protein 3 (CUL3) / speckle-type POZ (poxvirus and zinc finger protein) protein (SPOP) E3 ubiquitin ligase in paclitaxel-resistant cells. Collectively, these findings suggest that DRAK1 may serve as a potential predictive biomarker for overcoming paclitaxel resistance in cervical cancer.

Successful Full-Term Delivery via Selective Ectopic Embryo Reduction Accompanied by Uterine Cerclage in a Heterotopic Cesarean Scar Pregnancy: A Case Report and Literature Review.

Heterotopic cesarean scar pregnancy (HCSP) is a combination of cesarean scar pregnancy (CSP) and intrauterine pregnancy (IUP). Cesarean scar pregnancy is accompanied by life-threatening complications, such as uterine rupture and massive bleeding. Herein, we present a case of HCSP treated with selective potassium chloride injection into the CSP under ultrasonography in association with uterine cerclage to control vaginal bleeding; this led to a successful IUP preservation and full-term delivery. Additionally, we will review several previous reports on HCSP management, including our case.

ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer.

Although accumulating evidence indicates that alternative splicing is aberrantly altered in many cancers, the functional mechanism remains to be elucidated. Here, we show that epithelial and mesenchymal isoform switches of leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) regulated by epithelial splicing regulatory protein 1 (ESRP1) correlate with metastatic potential of gastric cancer cells. We found that expression of the splicing variants of LRRFIP2 was closely correlated with that of ESRP1. Surprisingly, ectopic expression of the mesenchymal isoform of LRRFIP2 (variant 3) dramatically increased liver metastasis of gastric cancer cells, whereas deletion of exon 7 of LRRFIP2 by the CRISPR/Cas9 system caused an isoform switch, leading to marked suppression of liver metastasis. Mechanistically, the epithelial LRRFIP2 isoform (variant 2) inhibited the oncogenic function of coactivator-associated arginine methyltransferase 1 (CARM1) through interaction. Taken together, our data reveals a mechanism of LRRFIP2 isoform switches in gastric cancer with important implication for cancer metastasis.

Authentication of pomegranate juice using multidimensional analysis of its metabolites.

With the growing popularity and demand of pomegranate juice, its adulteration has also steadily increased. In this study, to authenticate pure or adulterated juice, the major components of pomegranate juice were compared with those of grape, peach, and apple juices (which are common adulterants in pomegranate juice) using liquid chromatography-electrospray-tandem mass spectrometry, ion chromatography, and inductively coupled plasma spectrometry. The various parameters evaluated were as follows: the ratio of malic acid to citric acid content, presence of tartaric acid, and levels of glucose, fructose, and mannitol, and sucrose. Potassium was the most abundant mineral in pomegranate juice, and the content ratio of other minerals/potassium did not exceed 0.1. The reliability of this method was confirmed in blind tests and monitoring experiments with commercial pomegranate juice. In conclusion, a simple and effective method was developed to detect adulteration in pomegranate juice.

Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells.

Although tetraarsenic hexoxide is known to exert an anti-tumor effect by inducing apoptosis in various cancer cells, its effect on other forms of regulated cell death remains unclear. Here, we show that tetraarsenic hexoxide induces the pyroptotic cell death through activation of mitochondrial reactive oxygen species (ROS)-mediated caspase-3/gasdermin E (GSDME) pathway, thereby suppressing tumor growth and metastasis of triple-negative breast cancer (TNBC) cells. Interestingly, tetraarsenic hexoxide-treated TNBC cells exhibited specific pyroptotic characteristics, including cell swelling, balloon-like bubbling, and LDH releases through pore formation in the plasma membrane, eventually suppressing tumor formation and lung metastasis of TNBC cells. Mechanistically, tetraarsenic hexoxide markedly enhanced the production of mitochondrial ROS by inhibiting phosphorylation of mitochondrial STAT3, subsequently inducing caspase-3-dependent cleavage of GSDME, which consequently promoted pyroptotic cell death in TNBC cells. Collectively, our findings highlight tetraarsenic hexoxide-induced pyroptosis as a new therapeutic strategy that may inhibit cancer progression of TNBC cells.

KCDC Risk Assessments on the Initial Phase of the COVID-19 Outbreak in Korea.

OBJECTIVES: This study aims to evaluate the risk assessments of coronavirus 2019 (COVID-19) in the Korea Centers for Disease Control and Prevention (KCDC), from the point of detection to the provision of basic information to the relevant public health authorities. METHODS: To estimate the overall risk of specific public health events, probability, and impact at the country-level were evaluated using available information. To determine the probability of particular public health events, the risk of importation and risk of transmission were taken into consideration. KCDC used 5 levels ("very low," "low," "moderate," "high," and "very high") for each category and overall risk was eventually decided. RESULTS: A total of 8 risk assessments were performed on 8 separate occasions between January 8th to February 28th, 2020, depending on the detection and report of COVID-19 cases in other countries. The overall risk of the situation in each assessment increased in severity over this period: "low" (first), "moderate" (second), "high" (third), "high" (fourth), "high" (fifth), "high" (sixth), "high" (seventh), and "very high" (eighth). CONCLUSION: The KCDC's 8 risk assessments were utilized to activate national emergency response mechanisms and eventually prepare for the pandemic to ensure the containment and mitigation of COVID-19 with non-pharmaceutical public health measures.

Destablilization of TRAF6 by DRAK1 Suppresses Tumor Growth and Metastasis in Cervical Cancer Cells.

The adaptor protein TNF receptor-associated factor 6 (TRAF6) is a key mediator in inflammation. However, the molecular mechanisms controlling its activity and stability in cancer progression remain unclear. Here we show that death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK1) inhibits the proinflammatory signaling pathway by targeting TRAF6 for degradation, thereby suppressing inflammatory signaling-mediated tumor growth and metastasis in advanced cervical cancer cells. DRAK1 bound directly to the TRAF domain of TRAF6, preventing its autoubiquitination by interfering with homo-oligomerization, eventually leading to autophagy-mediated degradation of TRAF6. Depletion of DRAK1 in cervical cancer cells resulted in markedly increased levels of TRAF6 protein, promoting activation of the IL1ß signaling-associated pathway and proinflammatory cytokine production. DRAK1 was specifically underexpressed in metastatic cervical cancers and inversely correlated with TRAF6 expression in mouse xenograft model tumor tissues and human cervical tumor tissues. Collectively, our findings highlight DRAK1 as a novel antagonist of inflammation targeting TRAF6 for degradation that limits inflammatory signaling-mediated progression of advanced cervical cancer. SIGNIFICANCE: Serine/threonine kinase DRAK1 serves a unique role as a novel negative regulator of the inflammatory signaling mediator TRAF6 in cervical cancer progression.