Factors Associated with Acute Kidney Injury Occurrence and Prognosis in Rhabdomyolysis at the Emergency Department.

Background and Objectives: This study aimed to analyze patients with rhabdomyolysis who presented to emergency departments and identify their distribution of related disease and prognostic factors. Materials and Methods: A retrospective cohort study was conducted on patients with rhabdomyolysis who presented to emergency departments over a 10-year period. Patient data, including patients' demographic variables (sex and age), mode of arrival, final diagnosis, statin use, rhabdomyolysis trigger factors, and levels of serum creatine phosphokinase (CPK), myoglobin, creatinine, sodium, potassium, phosphate, calcium, and lactate, were analyzed. Univariate and multivariate logistic regression analyses were conducted to identify the predictive factors of acute kidney injury (AKI). Results: Among the patients, 268 (65.6%) were found to have trigger factors without underlying diseases. Furthermore, 115 (28.2%) patients developed AKI. This comprehensive study sheds light on the diverse factors influencing the occurrence of AKI in rhabdomyolysis and provides insights into AKI predictive markers. Furthermore, we analyzed the cases by dividing them into six groups: occurrence of AKI, occurrence of infection, and simple or complex rhabdomyolysis. CPK time course was found to be important in clinical prognosis, such as AKI occurrence, dialysis or not, and mortality. Conclusions: Age, statin use, elevated creatinine and lactate levels, and initial serum CPK level emerged as significant predictors of AKI. CPK time course was also found to be an important factor in predicting the clinical outcomes of patients with rhabdomyolysis.

4-O-Methylascochlorin-Mediated BNIP-3 Expression Controls the Balance of Apoptosis and Autophagy in Cervical Carcinoma Cells.

4-O-methylascochlorin (MAC) is a 4-fourth carbon-substituted derivative of ascochlorin, a compound extracted from a phytopathogenic fungus Ascochyta viciae. MAC induces apoptosis and autophagy in various cancer cells, but the effects of MAC on apoptosis and autophagy in cervical cancer cells, as well as how the interaction between apoptosis and autophagy mediates the cellular anticancer effects are not known. Here, we investigated that MAC induced apoptotic cell death of cervical cancer cells without regulating the cell cycle and promoted autophagy by inhibiting the phosphorylation of serine-threonine kinase B (Akt), mammalian target of rapamycin (mTOR), and 70-kDa ribosomal protein S6 kinase (p70S6K). Additional investigations suggested that Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP-3), but not Hypoxia-inducible factor 1 alpha (HIF-1α), is a key regulator of MAC-induced apoptosis and autophagy. BNIP-3 siRNA suppressed MAC-induced increases in cleaved- poly (ADP-ribose) polymerase (PARP) and LC3II expression. The pan-caspase inhibitor Z-VAD-FMK suppressed MAC-induced cell death and enhanced MAC-induced autophagy. The autophagy inhibitor chloroquine (CQ) enhanced MAC-mediated cell death by increasing BNIP-3 expression. These results indicate that MAC induces apoptosis to promote cell death and stimulates autophagy to promote cell survival by increasing BNIP-3 expression. This study also showed that co-treatment of cells with MAC and CQ further enhanced the death of cervical cancer cells.

Rg3-enriched red ginseng extracts enhance apoptosis in CoCl2-stimulated breast cancer cells by suppressing autophagy.

Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl2, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl2-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl2-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.

Prognostic value of arterial stiffness in menopausal women.

OBJECTIVE: Because menopausal women have an increased cardiovascular risk, risk stratification is very crucial in this population. This study aimed to verify the prognostic value of arterial stiffness in menopausal women. METHODS: We retrospectively analyzed 2,917 menopausal women (age >55y) without overt cardiovascular disease who underwent brachial-ankle pulse wave velocity measurement. The primary endpoint was a composite of clinical events, including all-cause death, nonfatal myocardial infarction, coronary revascularization, and stroke, hereafter referred to as major adverse cardiovascular events. Propensity score matching and inverse probability-treatment weighting analysis were used to balance differences in baseline participant characteristics. RESULTS: The mean participant age was 66.8 ±â€Š7.7 years. During a median follow-up period of 4.0 (interquartile range of 1.9-6.3) years, the primary outcome was noted in 56 cases (1.9%). Pulse wave velocity was significantly higher in participants with the primary outcome than in those without (1,947 ±â€Š388 vs 1,690 ±â€Š348 cm/s; P  < 0.001). For every 100 cm/s increase in pulse wave velocity, the hazard ratio for the primary endpoint increased by 1.15 times (95% confidence interval, 1.08-1.22; P  < 0.001) in multivariable Cox regression analysis. A pulse wave velocity > 1,613 cm/s was associated with increased risk of the primary endpoint in the same multivariable analysis (hazard ratio, 3.06; 95% confidence interval, 1.40-6.68; P  = 0.005). The results were consistent after propensity score matching and inverse probability-treatment weighting analysis. CONCLUSIONS: Elevated brachial-ankle pulse wave velocity was associated with the occurrence of major adverse cardiovascular events in menopausal women without cardiovascular disease and may represent a useful screening tool.

4-O-methylascochlorin-stimulated HIF-1α expression induces the epithelial mesenchymal transition and cell survival in breast cancer cells.

4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin, promotes accumulation of HIF-1α. In this study, we investigated the molecular mechanisms of the effect of MAC on cell migration and mesenchymal epithelial transition (EMT) processes in breast cancer cells. MAC upregulated cell motility and migration regardless of cell viability, and promoted EMT features by regulating EMT-related proteins and transcription. In addition, the MAC-induced increase in the EMT was closely related to activation of HIF-1α expression. However, the MAC-induced EMT was not associated with AMPK phosphorylation or intracellular ROS, which stimulate HIF-1α expression. Similarly, HIF-1α-mediated autophagy induced by MAC was not related to EMT-related proteins. Inhibition of HIF-1α activity inhibited MAC-stimulated cell migration and increased MAC-induced cell death, indicating that HIF-1α activation is important for MAC-mediated cell migration and survival in breast cancer cells. Together, these results suggest that MAC can be used to investigate the link between HIF-1α activation and other oncogenes or tumor suppressors in breast cancer cells.

Pathological and Genomic Findings of Erysipelothrix rhusiopathiae Isolated From a Free-Ranging Rough-Toothed Dolphin Steno bredanensis (Cetacea: Delphinidae) Stranded in Korea.

Erysipelas, caused by Erysipelothrix rhusiopathiae, is considered one of the most serious infectious diseases of captive and free-ranging cetaceans worldwide, as these animals are known to be highly susceptible to the bacterial infections. The potential diversity between E. rhusiopathiae isolates from captive cetaceans has been previously described; however, the microbiological features of the free-ranging cetacean isolates remain unclear. Here, we describe a case of bacteremia in a rough-toothed dolphin (Steno bredanensis) caused by E. rhusiopathiae. Additionally, we present the first genomic features of the bacteria from free-ranging cetacean individuals. Histopathological and microbial examinations revealed that E. rhusiopathiae caused bacteremia and systemic infection in the dolphin. The genome of the isolated E. rhusiopathiae strain KC-Sb-R1, which was classified as Clade 1 possessing SpaB gene, was clearly differentiated from the other swine-isolated E. rhusiopathiae, and the comparison of its serovar-defining chromosomal region revealed that our isolate was greatly similar to those of other previously reported serovar 2/15 isolates, including the captive-dolphin isolate. Moreover, most of the potential virulence factors in the strain KC-Sb-R1 were similar to those in the strain Fujisawa. Further, a potential cytotoxicity of the isolate was confirmed, suggesting that marine mammal-isolated E. rhusiopathiae could possess strong pathogenic potential in other animals, including humans. These results would further increase our understanding on the risk factors for controlling zoonotic pathogens of emerging infectious diseases in captive or free-ranging cetaceans, and also provide important insight into the diversity of E. rhusiopathiae in animals.

Emergence of Third-Generation Cephalosporin-Resistant Morganella morganii in a Captive Breeding Dolphin in South Korea.

The emergence of antimicrobial resistant (AMR) strains of Morganella morganii is increasingly being recognized. Recently, we reported a fatal M. morganii infection in a captive bottlenose dolphin (Tursiops truncatus) bred at a dolphinarium in South Korea. According to our subsequent investigations, the isolated M. morganii strain KC-Tt-01 exhibited extensive resistance to third-generation cephalosporins which have not been reported in animals. Therefore, in the present study, the genome of strain KC-Tt-01 was sequenced, and putative virulence and AMR genes were investigated. The strain had virulence and AMR genes similar to those of other M. morganii strains, including a strain that causes human sepsis. An amino-acid substitution detected at the 86th residue (Arg to Cys) of the protein encoded by ampR might explain the extended resistance to third-generation cephalosporins. These results indicate that the AMR M. morganii strain isolated from the captive dolphin has the potential to cause fatal zoonotic infections with antibiotic treatment failure due to extended drug resistance, and therefore, the management of antibiotic use and monitoring of the emergence of AMR bacteria are urgently needed in captive cetaceans for their health and conservation.

Genomic insights into Photobacterium damselae subsp. damselae strain KC-Na-1, isolated from the finless porpoise (Neophocaena asiaeorientalis).

Photobacterium damselae subsp. damselae (PDD) is a marine bacterium that can infect a variety of marine animals and humans. Although this bacterium has been isolated from several stranded dolphins and whales, its pathogenic role in cetaceans is still unclear. In this study, we report the complete genome of PDD strain KC-Na-1 isolated from a finless porpoise (Neophocaena asiaeorientalis) rescued from the South Sea (Republic of Korea). The sequenced genome comprised two chromosomes and four plasmids. Among the recently identified major virulence factors in PDD, only phospholipase (plpV) was found in strain KC-Na-1. Interestingly, two genes homologous to Vibrio thermostable direct hemolysin (tdh) and its transcriptional regulator toxR, which are known virulence factors associated with Vibrio parahaemolyticus, were encoded on the plasmid pPDD-Na-1-3. Based on these results, strain KC-Na-1 may have potential pathogenicity in humans and other marine animals and also could act as a potential virulent strain. To the best of our knowledge, this is the first report of the complete genome sequence of P. damselae.

Characterization of the complete mitochondrial genome and phylogenetic analysis of the common dolphin Delphinus delphis (Cetacea: Delphinidae).

We report the complete mitogenome of the common dolphin, Delphinus delphis. Overall structure of the 16,387 bp mitogenome was very similar to those of other delphinid species, including the ancient D. delphis individuals. Multigene phylogeny revealed that D. delphis was most closely related to Stenella coeruleoalba, and clustered well with other species within the subfamily Delphininae.

First report of the occurrence and whole-genome characterization of Edwardsiella tarda in the false killer whale (Pseudorca crassidens).

Although several Edwardsiella tarda infections have been reported, its pathogenic role in marine mammals has not been investigated at the genome level. We investigated the genome of E. tarda strain KC-Pc-HB1, isolated from the false killer whale (Pseudorca crassidens) found bycaught in South Korea. The obtained genome was similar to that of human pathogenic E. tarda strains, but distinct from other Edwardsiella species. Although type III and VI secretion systems, which are essential for the virulence of other Edwardsiella species, were absent, several virulence-related genes involved in the pathogenesis of E. tarda were found in the genome. These results provide important insights into the E. tarda infecting marine mammals and give valuable information on potential virulence factors in this pathogen.

Development of implant loading device for animal study about various loading protocol: a pilot study.

PURPOSE: The aims of this pilot study were to introduce implant loading devices designed for animal study and to evaluate the validity of the load transmission ability of the loading devices. MATERIALS AND METHODS: Implant loading devices were specially designed and fabricated with two implant abutments and cast metal bars, and orthodontic expansion screw. In six Beagles, all premolars were extracted and two implants were placed in each side of the mandibles. The loading device was inserted two weeks after the implant placement. According to the loading protocol, the load was applied to the implants with different time and method,simulating early, progressive, and delayed loading. The implants were clinically evaluated and the loading devices were removed and replaced to the master cast, followed by stress-strain analysis. Descriptive statistics of remained strain (µÎµ) was evaluated after repeating three cycles of the loading device activation. Statistic analysis was performed using nonparametric, independent t-test with 5% significance level and Friedman's test was also used for verification. RESULTS: The loading devices were in good action. However, four implants in three Beagles showed loss of osseointegration. In stress-strain analysis, loading devices showed similar amount of increase in the remained strain after applying 1-unit load for three times. CONCLUSION: Specialized design of the implant loading device was introduced. The loading device applied similar amount of loads near the implant after each 1-unit loading. However, the direction of the loads was not parallel to the long axis of the implants as predicted before the study.