Tat-GSTpi Inhibits Dopaminergic Cells against MPP+-Induced Cellular Damage via the Reduction of Oxidative Stress and MAPK Activation.

Glutathione S-transferase pi (GSTpi) is a member of the GST family and plays many critical roles in cellular processes, including anti-oxidative and signal transduction. However, the role of anti-oxidant enzyme GSTpi against dopaminergic neuronal cell death has not been fully investigated. In the present study, we investigated the roles of cell permeable Tat-GSTpi fusion protein in a SH-SY5Y cell and a Parkinson's disease (PD) mouse model. In the 1-methyl-4-phenylpyridinium (MPP+)-exposed cells, Tat-GSTpi protein decreased DNA damage and reactive oxygen species (ROS) generation. Furthermore, this fusion protein increased cell viability by regulating MAPKs, Bcl-2, and Bax signaling. In addition, Tat-GSTpi protein delivered into the substantia nigra (SN) of mice brains protected dopaminergic neuronal cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our results indicate that the Tat-GSTpi protein inhibited cell death from MPP+- and MPTP-induced damage, suggesting that it plays a protective role during the loss of dopaminergic neurons in PD and that it could help to identify the mechanism responsible for neurodegenerative diseases, including PD.

Protective Effects of PEP-1-GSTA2 Protein in Hippocampal Neuronal Cell Damage Induced by Oxidative Stress.

Glutathione S-transferase alpha 2 (GSTA2), a member of the glutathione S-transferase family, plays the role of cellular detoxification against oxidative stress. Although oxidative stress is related to ischemic injury, the role of GSTA2 against ischemia has not been elucidated. Thus, we studied whether GSTA2 prevents ischemic injury by using the PEP-1-GSTA2 protein which has a cell-permeable protein transduction domain. We revealed that cell-permeable PEP-1-GSTA2 transduced into HT-22 cells and markedly protected cell death via the inhibition of reactive oxygen species (ROS) production and DNA damage induced by oxidative stress. Additionally, transduced PEP-1-GSTA2 promoted mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-κB) activation. Furthermore, PEP-1-GSTA2 regulated Bcl-2, Bax, cleaved Caspase-3 and -9 expression protein levels. An in vivo ischemic animal model, PEP-1-GSTA2, markedly prevented the loss of hippocampal neurons and reduced the activation of microglia and astrocytes. These findings indicate that PEP-1-GSTA2 suppresses hippocampal cell death by regulating the MAPK and apoptotic signaling pathways. Therefore, we suggest that PEP-1-GSTA2 will help to develop the therapies for oxidative-stress-induced ischemic injury.

Protective effect of GK2 fused BLVRA protein against oxidative stress-induced dopaminergic neuronal cell damage.

It is well known that oxidative stress is highly associated with Parkinson's disease (PD), and biliverdin reductase A (BLVRA) is known to have antioxidant properties against oxidative stress. In this study, we developed a novel N-acetylgalactosamine kinase (GK2) protein transduction domain (PTD) derived from adenosine A2A and fused with BLVRA to determine whether the GK2-BLVRA fusion protein could protect dopaminergic neuronal cells (SH-SY5Y) from oxidative stress in vitro and in vivo using a PD animal model. GK2-BLVRA was transduced into various cells, including SH-SY5Y cells, without cytotoxic effects, and this fusion protein protected SH-SY5Y cells and reduced reactive oxygen species production and DNA damage after 1-methyl-4-phenylpyridinium (MPP+ ) exposure. GK2-BLVRA suppressed mitogen-activated protein kinase (MAPK) activation and modulated apoptosis-related protein (Bcl-2, Bax, cleaved Caspase-3 and -9) expression levels. In the PD animal model, GK2-BLVRA transduced into the substantia nigra crossed the blood-brain barrier and markedly reduced dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animals. These results indicate that our novel PTD GK-2 is useful for the transduction of protein, and GK2-BLVRA exhibits a beneficial effect against dopaminergic neuronal cell death in vitro and in vivo, suggesting that BLVRA can be used as a therapeutic agent for PD.

Molecular Typing on Human Blood Reveals the Borrelia afzelii Infection in Korea.

Lyme disease is a tick-borne infection in Korea. Here, clinical samples were collected from a 72-year old patient, with sudden onset of fever on April, 2018. The patient was passed away after 3rd day of doxycycline administration. The molecular diagnostic tests, nested polymerase chain reaction targeting 5S-23S rRNA intergenic spacer region (IGS) and multilocus sequence typing (MLST), showed positive for Borrelia afzelii from blood. Further, mutations in both 5S - 23S IGS and pepX allele of MLST were determined. Herein, we report the expected first death case by B. afzelii infection in Korea.

Obesity and abdominal obesity are risk factors for airway obstructive diseases in Korean women: nationwide population-based cohort study.

OBJECTIVE: Existing studies show that women are more susceptible to chronic obstructive pulmonary disease (COPD) and asthma, and that obesity affects the risk of these airway obstructive diseases. We aimed to determine the effect of body mass index (BMI) and waist circumference (WC) on COPD and asthma development in premenopausal and postmenopausal women. METHODS: This nationwide population-based cohort study included 1,644,635 women ages ≥30 years without diagnosis of COPD or asthma, who underwent national cancer screening in 2009. We classified them as premenopausal and postmenopausal women based on their menopause status at the time of cancer screening. Baseline BMI and WC were measured, and they were classified into five BMI groups (<18.5 kg/m2, 18.5-23 kg/m2, 23-25 kg/m2, 25-30 kg/m2, and ≥30 kg/m2) and WC groups (<60 cm, 65-75 cm, 75-85 cm, 85-95 cm, and ≥95 cm). The hazard ratios (HRs) for COPD and asthma were measured for each group. RESULTS: Regardless of the menopausal status, the high BMI and WC groups had a significantly higher COPD and asthma incidence than that of the normal group, and the HRs increased further with increases in BMI and WC. However, the HR in the underweight group was significantly higher among the postmenopausal women. The HR for asthma in the obese group was significantly higher for both premenopausal and postmenopausal women. The HR for COPD was significantly higher in the group with a WC of ≥95 cm for both premenopausal and postmenopausal women, respectively; the HR for asthma was also significantly higher in this group. CONCLUSIONS: Obesity and abdominal obesity are risk factors for COPD and asthma in premenopausal and postmenopausal Korean women. Controlling weight and maintaining a healthy body shape can help prevent COPD and asthma in women.

A Longitudinal Retrospective Observational Study on Obesity Indicators and the Risk of Impaired Fasting Glucose in Pre- and Postmenopausal Women.

The impact of obesity could differ according to menopausal status since women undergo significant physiologic and metabolic changes due to menopause. We investigated the association between various major obesity indicators and the risk of impaired fasting glucose (IFG) according to menopausal status using nationally representative data. A total of 571,286 premenopausal and 519,561 postmenopausal women who underwent both Korean National Health Insurance Service (NHIS) cancer screening in 2009 and health check-ups in 2017 were analyzed. Multivariate logistic regression analyses were used to assess the effect of independent variables of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in 2009, on dependent variable IFG in 2017. After adjusting for potential confounders, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of developing IFG were analyzed. In the premenopausal group, the OR of obese BMI (≥25 kg/m2, <30 kg/m2) women was increased to 2.228 (95% CI: 2.139−2.321) compared to the normal BMI (≥18.5, <23 kg/m2) women as a reference. In the postmenopausal group, there was also a higher OR of 1.778 (95% CI: 1.715−1.843) in the obese BMI women compared to the normal group. A similar association of increasing ORs for IFG was shown in both groups when stratified by WC and WHtR. This nationwide study revealed that obesity and abdominal obesity, defined by various obesity indicators, consistently increased odds of acquiring IFG after 8 years in both pre- and postmenopausal groups, with the association being more robust in the premenopausal group. Our findings suggest that weight management and lifestyle modification may require more attention in premenopausal women.

Sirolimus-eluting cobalt-chrome alloy stent suppresses stent-induced tissue hyperplasia in a porcine Eustachian tube model.

Various preclinical studies with developed Eustachian tube (ET) stents are in progress but have not yet been clinically applied. ET stent is limited by stent-induced tissue hyperplasia in preclinical studies. The effectiveness of sirolimus-eluting cobalt-chrome alloy stent (SES) in suppressing stent-induced tissue hyperplasia after stent placement in the porcine ET model was investigated. Six pigs were divided into two groups (i.e., the control and the SES groups) with three pigs for each group. The control group received an uncoated cobalt-chrome alloy stent (n = 6), and the SES group received a sirolimus-eluting cobalt-chrome alloy stent (n = 6). All groups were sacrificed 4 weeks after stent placement. Stent placement was successful in all ETs without procedure-related complications. None of the stents was able to keep its round shape as original, and mucus accumulation was observed inside and around the stent in both groups. On histologic analysis, the tissue hyperplasia area and the thickness of submucosal fibrosis were significantly lower in the SES group than in the control group. SES seems to be effective in suppressing stent-induced tissue hyperplasia in porcine ET. However, further investigation was required to verify the optimal stent materials and antiproliferative drugs.

Blood pressure and mortality after percutaneous coronary intervention: a population-based cohort study.

Revascularization procedures, including percutaneous coronary intervention (PCI), for coronary artery disease (CAD) are increasingly performed in Korea. However, studies on blood pressure control targets in these patients remain insufficient. To assess the relationship between baseline blood pressure and all-cause mortality in CAD patients who underwent PCI. A population-based retrospective cohort study based on the national claims database of the Korean National Health Insurance System, which represents the entire Korean population. A total 38,330 patients with a history of PCI for CAD between 2005 and 2008 were recruited and followed up for all-cause mortality until December 31, 2017. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and they were classified into eight SBP and DBP groups each. The hazard ratios (HRs) for all-cause mortality were measured for each group. The pattern of SBP and DBP in this population followed a J-curve relationship for all-cause mortality, with the nadir point at 119 and 74 mmHg, respectively. In subjects aged > 60 years, high SBP (≥ 160 mmHg) and high DBP (≥ 90 mmHg) were significantly related to death. Moreover, in subjects aged > 60 years, low DBP (< 70 mmHg) was significantly related to mortality. There is a J-curve relationship between baseline blood pressure and all-cause mortality in patients who underwent PCI, and intensive lowering of blood pressure may be beneficial for these patients. However, the elderly population needs more attention as excessive BP lowering, particularly DBP, could instead increase the risk of death.

Relationship between blood pressure levels and ischemic stroke, myocardial infarction, and mortality in very elderly patients taking antihypertensives: a nationwide population-based cohort study.

BACKGROUND: In the very elderly, "the lower the better" hypothesis has constantly been contradicted by randomized control trials and various cohort studies, but inconsistency in results led to unclear blood pressure treatment targets. This study aimed to assess the relationship between baseline blood pressure (BP) and ischemic stroke, myocardial infarction, and all-cause mortality in very elderly people treated for hypertension. METHODS: This large population-based retrospective cohort study was based on the national claims database of the Korean National Health Insurance System, which covers the entire Korean population. 374,250 participants aged ≥ 75 years taking antihypertensive agents were recruited, excluding patients with a history of previous ischemic stroke or myocardial infarction. RESULTS: Systolic BP (SBP) followed a J curve for ischemic stroke and a U curve for all-cause mortality, with nadir ranges of 120 to 129 mmHg and 140 to 149 mmHg, respectively. While increasing diastolic BP (DBP) generally resulted in higher HRs for ischemic stroke, HRs for myocardial infarction and all-cause mortality significantly increased only when DBP was ≥ 80 mmHg and ≥ 90 mmHg, respectively. The SBP/DBP combination analysis showed that even with SBP < 130 mmHg, higher DBP ≥ 90 mmHg had higher HRs for all three outcomes compared to the reference group (130 to 149 / < 80 mmHg). CONCLUSIONS: There were no further benefits or even harm below certain BP levels for ischemic stroke, myocardial infarction, and all-cause mortality in very elderly hypertensive patients.

Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling.

Thioredoxin 1 (Trx1) serves a central role in redox homeostasis. It is involved in numerous other processes, including oxidative stress and apoptosis. However, to the best of our knowledge, the role of Trx1 in inflammation remains to be explored. The present study investigated the function and mechanism of cell permeable fused Tat-Trx1 protein in macrophages and a mouse model. Transduction levels of Tat-Trx1 were determined via western blotting. Cellular distribution of transduced Tat-Trx1 was determined by fluorescence microscopy. 2',7'-Dichlorofluorescein diacetate and TUNEL staining were performed to determine the production of reactive oxygen species and DNA fragmentation. Protein and gene expression were measured by western blotting and reverse transcription-quantitative PCR (RT-qPCR), respectively. Effects of skin inflammation were determined using hematoxylin and eosin staining, changes in ear weight and ear thickness, and RT-qPCR in ear edema animal models. Transduced Tat-Trx1 inhibited lipopolysaccharide-induced cytotoxicity and activation of NF-κB, MAPK and Akt. Additionally, Tat-Trx1 markedly reduced the production of inducible nitric oxide synthase, cyclooxygenase-2, IL-1ß, IL-6 and TNF-α in macrophages. In a 12-O-tetradecanoylphorbol-13-acetate-induced mouse model, Tat-Trx1 reduced inflammatory damage by inhibiting inflammatory mediator and cytokine production. Collectively, these results demonstrated that Tat-Trx1 could exert anti-inflammatory effects by inhibiting the production of pro-inflammatory mediators and cytokines and by modulating MAPK signaling. Therefore, Tat-Trx1 may be a useful therapeutic agent for diseases induced by inflammatory damage.

Association between body composite indices and vertebral fractures in pre and postmenopausal women in Korea.

The association between obesity and vertebral fracture remains controversial. This study aimed to investigate the association between obesity/abdominal obesity and vertebral fracture according to menopausal status. This nationwide population-based epidemiologic study collected data from the Korean National Health Insurance Services to investigate the association between obesity/abdominal obesity and vertebral fracture in pre and postmenopausal women who underwent national cancer screening in 2009. We used three body composite indices of obesity, body mass index, waist circumference and waist-to-height ratio, to classify participants into obesity and abdominal obesity groups. In both pre and postmenopausal groups, participants with obesity showed a higher risk of vertebral fracture and the association was stronger in those with abdominal obesity (p < 0.001). Participants with obesity showed a high risk of vertebral fracture, and the association was stronger in participants with abdominal obesity (p < 0.001). In both pre and postmenopausal groups, participants with obesity showed a higher risk of vertebral fracture (adjusted HR, 1.24; 95% CI, 1.19-1.30), (adjusted HR, 1.04; 95% CI, 1.03-1.05, and those with abdominal obesity showed even higher risk of vertebral fractures (adjusted HR, 1.35; 95% CI, 1.27-1.43), (adjusted HR, 1.13; 95% CI, 1.11-1.14). Vertebral fracture risk is higher in pre and postmenopausal women with obesity and even higher in those with abdominal obesity. Therefore, weight management can prevent vertebral fractures.

Utilization of an Intracellular Calcium Mobilization Assay for the Screening of Transduced FK506-Binding Proteins.

FK506-binding proteins (FKBPs) belong to the immunophilin family and are linked to various disease states, including the inflammatory response. The inhibition of cytokine and chemokine expression in addition to positive effects of FKBPs on corneal inflammation in animal models suggests that they may be used for ophthalmic delivery in the treatment of dry eye disease. To pass the effective barriers protecting eye tissues, testing the transduction domains of FKBPs is essential. However, monitoring their transduction efficiencies is not a simple task. The quantitative measurement of FKBP interactions was performed using a cell model with a specific G protein-coupled receptor, as FKBPs had been known to act at the inositol 1,4,5-trisphosphate receptor (IP3R) leading to the inhibition of intracellular calcium mobilization. Because of its luminescence amplitude and stability, human urotensin II receptor was expressed in aequorin parental cells to measure the action of selected FKBPs. This luminescence-based functional assay platform exhibited a high signal-to-background ratio of more than 100 and a Z' factor at 0.6204. As expected, changes in the sequence of the transduction domain affected the function of the FKBPs. The intracellular calcium mobilization assay with selected FKBPs represented a robust and reliable platform to screen initial candidates. Although the precise nature of the control that FKBPs exert on the IP3R is uncertain, this approach can be used to develop innovative anti-inflammatory treatments for dry eye disease by optimizing protein transduction domain sequences.

PEP-1-GLRX1 Reduces Dopaminergic Neuronal Cell Loss by Modulating MAPK and Apoptosis Signaling in Parkinson's Disease.

Parkinson's disease (PD) is characterized mainly by the loss of dopaminergic neurons in the substantia nigra (SN) mediated via oxidative stress. Although glutaredoxin-1 (GLRX1) is known as one of the antioxidants involved in cell survival, the effects of GLRX1 on PD are still unclear. In this study, we investigated whether cell-permeable PEP-1-GLRX1 inhibits dopaminergic neuronal cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We showed that PEP-1-GLRX1 protects cell death and DNA damage in MPP+-exposed SH-SY5Y cells via the inhibition of MAPK, Akt, and NF-κB activation and the regulation of apoptosis-related protein expression. Furthermore, we found that PEP-1-GLRX1 was delivered to the SN via the blood-brain barrier (BBB) and reduced the loss of dopaminergic neurons in the MPTP-induced PD model. These results indicate that PEP-1-GLRX1 markedly inhibited the loss of dopaminergic neurons in MPP+- and MPTP-induced cytotoxicity, suggesting that this fusion protein may represent a novel therapeutic agent against PD.

Transduced Tat-PRAS40 prevents dopaminergic neuronal cell death through ROS inhibition and interaction with 14-3-3σ protein.

Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and activated mTORC1 plays important roles for cellular survival in response to oxidative stress. However, the roles of PRAS40 in dopaminergic neuronal cell death have not yet been examined. Here, we examined the roles of Tat-PRAS40 in MPP+- and MPTP-induced dopaminergic neuronal cell death. Our results showed that Tat-PRAS40 effectively transduced into SH-SY5Y cells and inhibited DNA damage, ROS generation, and apoptotic signaling in MPP+-induced SH-SY5Y cells. Further, these protective mechanisms of Tat-PRAS40 protein display through phosphorylation of Tat-PRAS40, Akt and direct interaction with 14-3-3σ protein, but not via the mTOR-dependent signaling pathway. In a Parkinson's disease animal model, Tat-PRAS40 transduced into dopaminergic neurons in mouse brain and significantly protected against dopaminergic cell death by phosphorylation of Tat-PRAS40, Akt and interaction with 14-3-3σ protein. In this study, we demonstrated for the first time that Tat-PRAS40 directly protects against dopaminergic neuronal cell death. These results indicate that Tat-PRAS40 may provide a useful therapeutic agent against oxidative stress-induced dopaminergic neuronal cell death, which causes diseases such as PD.

Tat­aldose reductase prevents dopaminergic neuronal cell death by inhibiting oxidative stress and MAPK activation.

Aldose reductase (AR) is known to detoxify aldehydes and prevent oxidative stress. Although AR exerts antioxidant effects, the role of AR in Parkinson's disease (PD) remains unclear. The objective of the present study was to investigate the protective effects of AR protein against 1­methyl­4­phenylpyridinium (MPP+)­induced SH­SY5Y cell death and 1­methyl­4­phenyl­1,2,3,6­tetrahydropyridine (MPTP)­induced PD in a mouse model using the cell permeable Tat­AR fusion protein. The results revealed that when Tat­AR protein was transduced into SH­SY5Y cells, it markedly protected the cells against MPP+­induced death and DNA fragmentation. It also reduced the activation of mitogen-activated protein kinase (MAPKs) and regulated the expression levels of Bcl­2, Bax and caspase­3. Immunohistochemical analysis revealed that when Tat­AR protein was transduced into the substantia nigra (SN) of mice with PD, it markedly inhibited dopaminergic neuronal cell death. Therefore, Tat­AR may be useful as a therapeutic protein for PD.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Tick-borne rickettsiae in Midwestern region of Republic of Korea.

To identify spotted fever group (SFG) rickettsiae among ticks collected by dragging at eight sites in three provinces of the midwestern region of the Republic of Korea (ROK), genus- and species-specific quantitative real-time PCR (qPCR) assays and sequencing were performed. DNA was extracted from a total of 2,312 ticks that were assayed individually (n=140) or in pools (n=444), resulting in a total of 584 individual and pooled tick samples. The 584 tick samples were screened with the genus-specific qPCR assay (Rick17b) and produced 265 (45.38%) positive reactions [individual (n=64) and pooled (n=101) samples]. Of these genus-specific positive samples, 57 (21.51%) were identified as Candidatus Rickettsia longicornii and 48 (18.11%) were identified as R. monacensis by species-specific qPCR assays. Subsequently, nested PCR (nPCR) was performed with 120 samples, which tested positive samples for genus-specific, but not species-specific, qPCR assays. The sequences of ompA and ompB genes showed how many close relatedness to Ca. R. longicornii and Ca. R. jingxinensis isolate Xian Hl-79, uncultured Rickettsia sp. Y27-1, Ca. R. tasmanensis strain T152, R. endosymbiont of H. longicornis tick 47, and R. koreansis strain CNH17-7. In conclusion, we successfully detected specific rickettsial agents using qPCR and a sequence-based analysis approach that demonstrated the prevalence of various tick-borne Rickettsia spp. in midwestern ROK.

Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury.

It is well known that oxidative stress participates in neuronal cell death caused production of reactive oxygen species (ROS). The increased ROS is a major contributor to the development of ischemic injury. Indoleamine 2,3-dioxygenase 1 (IDO-1) is involved in the kynurenine pathway in tryptophan metabolism and plays a role as an anti-oxidant. However, whether IDO-1 would inhibit hippocampal cell death is poorly known. Therefore, we explored the effects of cell permeable Tat-IDO-1 protein against oxidative stress-induced HT-22 cells and in a cerebral ischemia/reperfusion injury model. Transduced Tat-IDO-1 reduced cell death, ROS production, and DNA fragmentation and inhibited mitogen-activated protein kinases (MAPKs) activation in H2O2 exposed HT-22 cells. In the cerebral ischemia/ reperfusion injury model, Tat-IDO-1 transduced into the brain and passing by means of the blood-brain barrier (BBB) significantly prevented hippocampal neuronal cell death. These results suggest that Tat-IDO-1 may present an alternative strategy to improve from the ischemic injury. [BMB Reports 2020; 53(11): 582-587].

Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling.

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H2O2-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.

Molecular genetic analysis and clinical characterization of Rickettsia species isolated from the Republic of Korea in 2017.

Rickettsia sp. CNH17-7 was isolated from patients' blood and identified by gene analysis as a species distinct from Rickettsia japonica. In addition, similar rickettsial infection was confirmed in two species (Haemaphysalis longicornis and Ixodes nipponensis) of ticks and rodents in northeastern and southwestern provinces, Republic of Korea. Subsequently, the analysis of 16S rRNA, ompA, ompB and sca4 genes of isolate CNH17-7 revealed 100%, 99.68%, 99.57% and 99.44% sequence similarity with Rickettsia sp. HlR/D91 and Candidatus R. longicornii ROK-HL727. In this study, we report the isolation of a new Rickettsia sp. CNH17-7 and infection of different types of ticks with the same rickettsial agents.