Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb).

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma.

BACKGROUND: Necroptosis, a newly defined regulatable necrosis with membrane disruption, has been demonstrated to participate in trauma brain injury (TBI) related neuronal cell death. Heat shock protein 70 (HSP70) is a stress protein with neuroprotective activity, but the potential protective mechanisms are not fully understood. METHODS AND RESULTS: Here, we investigated the effects of HSP70 regulators in a cellular TBI model induced by traumatic neuronal injury (TNI) and glutamate treatment. We found that necroptosis occurred in cortical neurons after TNI and glutamate treatment. Neuronal trauma markedly upregulated HSP70 protein expression within 24 h. The results of immunostaining and lactate dehydrogenase release assay showed that necroptosis following neuronal trauma was inhibited by HSP70 activator TRC051384 (TRC), but promoted by the HSP70 inhibitor 2-phenylethyenesulfonamide (PES). In congruent, the expression and phosphorylation of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) were differently regulated by HSP70. Furthermore, the expression of HSP90α induced by neuronal trauma was further promoted by PES but decreased by TRC. The data obtained from western blot showed that the phosphorylation of RIPK3 and MLKL induced by HSP70 inhibition were reduced by RIPK3 inhibitor GSK-872 and HSP90α inhibitor geldanamycin (GA). Similarly, inhibition of HSP90α with GA could partially prevented the increased necroptosis induced by PES. CONCLUSIONS: Taken together, HSP70 activation exerted protective effects against neuronal trauma via inhibition of necroptosis. Mechanistically, the HSP90α-mediated activation of RIPK3 and MLKL is involved in these effects.

Sesquiterpene Lactones with Anti-Inflammatory Activity from the Halophyte Sonchus brachyotus DC.

There were five sesquiterpene lactones, belonging to the eudesmanolide class, isolated from the halophyte Sonchus brachyotus DC. The structures of the compounds were determined using spectroscopic methods, including 1D and 2D NMR spectra, MS data, and optical rotation values. Compounds 4 and 5 were characterized by the position of p-hydroxyphenylacetyl group in the sugar moiety. In the evaluation of anti-inflammatory effects on LPS-activated RAW264.7 macrophages, compound 1, 5α,6ßH-eudesma-3,11(13)-dien-12,6α-olide, potently suppressed the expression of iNOS and COS-2, as well as the production of TNF-α, IL-6, and IL-10. Treatment of 1 regulates the Nrf2/HO-1 pathway.

[Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway].

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

[Preparation of vitexin albumin nanoparticles and its pharmacokinetic study].

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

The ESCRT-I Subunit Tsg101 Plays Novel Dual Roles in Entry and Replication of Classical Swine Fever Virus.

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly contagious disease of swine with high morbidity and mortality that negatively affects the pig industry worldwide, in particular in China. Soon after the endocytosis of CSFV, the virus makes full use of the components of host cells to complete its life cycle. The endocytosis sorting complex required for transport (ESCRT) system is a central molecular machine for membrane protein sorting and scission in eukaryotic cells that plays an essential role in many physiological metabolic processes, including invasion and egress of envelope viruses. However, the molecular mechanism that ESCRT uses to regulate the replication of CSFV is unknown. In this study, we demonstrated that the ESCRT-I complex Tsg101 protein participates in clathrin-mediated endocytosis of CSFV and is also involved in CSFV trafficking. Tsg101 assists the virus in entering the host cell through the late endosome (Rab7 and Rab9) and finally reaching the lysosome (Lamp-1). Interestingly, Tsg101 is also involved in the viral replication process by interacting with nonstructural proteins 4B and 5B of CSFV. Finally, confocal microscopy showed that the replication complex of Tsg101 and double-stranded RNA (dsRNA) or NS4B and NS5B protein was close to the endoplasmic reticulum (ER), not the Golgi, in the cytoplasm. Collectively, our finding highlights that Tsg101 regulates the process of CSFV entry and replication, indicating that the ESCRT plays an important role in the life cycle of CSFV. Thus, ESCRT molecules could serve as therapeutic targets to combat CSFV infection.IMPORTANCE CSF, caused by CSFV, is a World Organization for Animal Health (OIE) notifiable disease and causes significant financial losses to the pig industry globally. The ESCRT machinery plays an important regulatory role in several members of the genera Flavivirus and Hepacivirus within the family Flaviviridae, such as hepatitis C virus, Japanese encephalitis virus, and dengue virus. Previous reports have shown that assembling and budding of these viruses require ESCRT. However, the role of ESCRT in Pestivirus infection remains to be elucidated. We determined the molecular mechanisms of the regulation of CSFV infection by the major subunit Tsg101 of ESCRT-I. Interestingly, Tsg101 plays an essential regulatory role in both clathrin-mediated endocytosis and genome replication of CSFV. Overall, the results of this study provide further insights into the molecular function of ESCRT-I complex protein Tsg101 during CSFV infection, which may serve as a molecular target for pestivirus inhibitors.

Evaluation of the Diagnostic Accuracy of Antibody Assays for Patients with Scrub Typhus.

This study was carried out to evaluate the accuracy of various antibody tests for scrub typhus, namely, the indirect immunofluorescence assay (IFA) from the Korea Centers for Disease Control and Prevention (KCDC) and four commercial kits (companies A to D). The test accuracy was based on the diagnosis of scrub typhus, as defined by a positive PCR or culture. In total, serum samples from 97 patients with scrub typhus and 200 non-scrub typhus patients were tested. The respective sensitivity and specificity of each test were as follows. For the KCDC IFA, sensitivity and specificity were 55.7% (95% confidence interval [CI], 45.2 to 65.8%) and 94.8% (95% CI, 90.4 to 97.3%) for IgM and 42.3% (95% CI, 32.3 to 52.7%) and 96.3% (95% CI, 92.6 to 98.5%) for IgG, with diagnostic cutoffs of ≥1:16 for IgM and ≥1:256 for IgG. For kit A, the sensitivity and specificity were 70.1% (95% CI, 59.8 to 78.8%) and 74.6% (95% CI, 67.6 to 80.6%) for total immunoglobulins, with a cutoff of ≥1:40. For kit B, the sensitivity and specificity were 64.3% (95% CI, 51.9 to 75.1%) and 94.9% (95% CI, 81.4 to 99.1%) for IgM and 67.1% (95% CI, 54.8 to 77.6%) and 74.4% (95% CI, 57.6 to 86.4%) for IgG. For kit C, the sensitivity and specificity were 53.6% (95% CI, 43.2 to 63.7%) and 99.5% (95% CI, 96.8 to 100%) for IgM and 36.1% (95% CI, 26.8 to 46.5%) and 100% (95% CI, 97.6 to 100%) for IgG. For kit D, the sensitivity and specificity were 73.2% (95% CI, 63.1 to 81.4%) and 89.5% (95% CI, 84.2 to 93.2%) for total immunoglobulins. These results are all unsatisfactory, highlighting an urgent need for the development of more highly sensitive and specific tests.

Molecular detection and identification of Culex flavivirus in mosquito species from Jeju, Republic of Korea.

BACKGROUND: Mosquito-borne flaviviruses are prime pathogens and have been a major hazard to humans and animals. They comprise several arthropod-borne viruses, including dengue virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus. Culex flavivirus (CxFV) is a member of the insect-specific flavivirus (ISF) group belonging to the genus Flavivirus, which is widely distributed in a variety of mosquito populations. METHODS: Viral nucleic acid was extracted from adult mosquito pools and subjected to reverse transcriptase nested polymerase chain reaction (PCR) using target-specific primers for detecting CxFV nonstructural protein 5 (NS5). The PCR-positive samples were then sequenced, and a phylogenetic tree was constructed, including reference sequences obtained from GenBank. RESULTS: 21 pools, belonging to Culex pipiens pallens (Cx. p. pallens) were found to be positive for the CxFV RNA sequence, with a minimum infection rate of 14.5/1000 mosquitoes. The phylogenetic analysis of the NS5 protein sequences indicated that the detected sequences were closely related to strains identified in China, with 95-98% sequence similarities. CONCLUSION: Our findings highlight the presence of CxFV in Cx. p. pallens mosquito species in Jeju province, Republic of Korea. This is the first study reporting the prevalence of CxFV in Culex Pipiens (Cx. pipiens) host in the Jeju province, which can create possible interaction with other flaviviruses causing human and animal diseases. Although, mosquito-borne disease causing viruses were not identified properly, more detailed surveillance and investigation of both the host and viruses are essential to understand the prevalence, evolutionary relationship and genetic characteristic with other species.

Follow-up investigation of antibody titers and diagnostic antibody cutoff values in patients with scrub typhus in South Korea.

BACKGROUND: Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Few follow-up studies have assessed antibody titers using serologic tests from various commercial laboratories and the Korea Centers for Disease Control and Prevention (KCDC). METHODS: A prospective study to assess the antibody titers in patients with scrub typhus and seroprevalence in individuals undergoing health checkups was conducted using results of immunofluorescence antibody assays (IFAs) and serologic tests, used by the KCDC and commercial laboratories, respectively. The following tests were performed simultaneously: (i) indirect IFA used by the KCDC to detect immunoglobulin (Ig) M and IgG, (ii) IFA used by a commercial laboratory to detect total Ig, and (iii) antibody tests using two commercially available kits. RESULTS: When the IgM and IgG cutoff values (≥1:16 and ≥1:256, respectively) used in the IFA and the total IgG cutoff values (≥1:40) were used in prospective follow-up investigations, the antibody positivity rates of 102 patients with scrub typhus were 44.1, 35.3, and 57.6%, respectively, within 5 days of symptom onset. Among 91 individuals who recovered from scrub typhus, the follow-up IgM, IgG, and total Ig positivity rates for 13 years were 37.4% (34/91), 22.0% (20/91), and 76.9% (70/91), respectively. Among 216 individuals undergoing health checkups, the seroprevalence of IgM was 4.2% (9/216); no seroprevalence of IgG was observed. CONCLUSIONS: IFAs used by the KCDC and the commercial laboratory and rapid commercial kits could not distinguish between patients who had recovered from scrub typhus and those who are currently infected with O. tsutsugamushi. In South Korea and other countries, where low antibody cutoff values are used, upward adjustments of cutoff values may be necessary.

A case of SFTS coinfected with E. coli bacteremia.

BACKGROUND: Severe fever thrombocytopenia syndrome virus (SFTSV) is the causative agent of severe fever thrombocytopenia syndrome (SFTS). SFTS is an emerging infectious disease, characterized by high fever, gastrointestinal symptoms, leukopenia, thrombocytopenia, and a high mortality rate. Until now, little importance has been given to the association of SFTS with leukocytosis and bacterial co-infection. CASE PRESENTATION: A 51-year old man visited our hospital with fever and low blood pressure. He was a farmer by occupation and often worked outdoors. He had a Foley catheter inserted due to severe BPH. Laboratory tests revealed thrombocytopenia, elevated liver function, and elevated CRP levels. He had marked leukocytosis, proteinuria, hematuria, and conjunctival hemorrhage. Initially, we thought that the patient was suffering from hemorrhagic fever with renal syndrome (HFRS). However, we confirmed SFTS through PCR and increasing antibody titer. However, his blood culture also indicated E. coli infection. CONCLUSION: SFTS displays characteristics of fever, thrombocytopenia, elevated liver function, and leukocytopenia. We described a case of SFTS with leukocytosis due to coinfection with E. coli. Since patients with SFTS usually have leukocytopenia, SFTS patients with leukocytosis are necessarily evaluated for other causes of leukocytosis. Here, we report the first case of an SFTS with concurrent E. coli bacteremia.

Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine.

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1-8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.

Stereochemical Determination of Fistularins Isolated from the Marine Sponge Ecionemia acervus and Their Regulatory Effect on Intestinal Inflammation.

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2), six fistularin compounds (1-6) were isolated from the marine sponge Ecionemia acervus (order Astrophorida). Based on stereochemical structure determination using Mosher's method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 (1) and -2 (2), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE2, TNF-α, IL-1ß, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 (1) and 19-deoxyfistularin-3 (4) showed the highest activity. These findings suggest the potential use of the marine sponge E. acervus and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.

The Effect of Long-lasting Permethrin Impregnated Socks on Tick Bite in Korea.

BACKGROUND: The risk of tick-borne diseases is decreased by increasing awareness and knowledge through prevention education. The aim of the present study was to evaluate the effect of long-lasting permethrin impregnated (LLPI) socks for tick bites. METHODS: A randomized open label study was conducted to determine the effectiveness of LLPI socks for prevention of tick bites among 367 adults living in a rural area. Participants completed questionnaires at the start of follow-up (July 2014) and at the end of follow-up (December 2014), and tick bites were reported. RESULTS: A total of 332 subjects completed the follow-up survey. The tick bite rate of the two groups was not significantly different (3.6% vs. 3.1%). But the tick bite rate of lower extremities of subjects wearing LLPI socks was significantly lower compared to that of subjects wearing general socks. CONCLUSION: The tick bite rate was not different between the two groups, but the tick bite rate of lower extremities of LLPI was significantly lower than general groups. Further study is needed to investigate the effect of LLPI clothes with larger populations.

Standardized Nursing Procedures for Fecal Microbiota Transplantation via Upper Endoscopy.

Fecal microbiota transplantation is an emerging treatment option that lacks a standardized nursing procedure. In our department, fecal microbiota transplantation has been undertaken to treat chronic hepatitis B and inflammatory bowel diseases since 2015. The fecal microbiota transplantation process involves various nursing measures that are critical for the successful completion of the procedures. In our center, a set of standardized nursing procedures has been established and has proved effective and operable. Standardized nursing procedures enhance the efficacy of fecal microbiota transplantation and alleviate the risk of treatment-related complications.

Analysis of the expression and association of retinoblastoma binding protein 6 with the JNK signaling pathway in prostate cancers.

This study aims to investigate the expression of retinoblastoma binding protein 6 (RBBP6) in prostate cancer (PCa) and its association with the c-Jun N-terminal kinase (JNK) pathway. Immunohistochemistry was used to detect RBBP6 and JNK1/2 expression in PCa and benign prostatic hyperplasia tissues. RBBP6 expression in PCa cells (LNCap, PC3, and DU145) and noncancerous prostate epithelial cells (RWPE-1) was determined by quantitative real-time polymerase chain reaction and western blot analysis. PC3 and DU145 cells were transfected with RBBP6 small interfering RNAs (siRNAs) to examine the biological characteristics. Anisomycin (a JNK activator) with/without RBBP6 siRNA was used to treat PC3 cells for further investigating the ramification of the RBBP6-mediated JNK pathway in PCa. PCa tissues and cells showed higher RBBP6 and JNK1/2 expression. RBBP6 was positively correlated with JNK1/2 in PCa tissues. Besides, RBBP6 expression was correlated to clinical tumor stage, lymph node metastasis, Gleason grade, preoperative prostate-specific antigen level, as well as prognosis of PCa. RBBP6 siRNA reduced cell proliferation, arrested cells at G2/M, and promoted cell apoptosis, and suppressed JNK pathway. In addition, migration and invasion decreased after the RBBP6 siRNA transfection with downregulated matrix metallopeptidase-2 (MMP-2) and MMP-9. Anisomycin promoted the proliferation, invasion, and migration of PC3 cells and inhibited PC3 cell apoptosis, which could be reversed by RBBP6 siRNA. RBBP6 expression was upregulated in PCa tissues and positively correlated with expression level of JNK1/2. With inhibition of RBBP6 expression, the proliferation, invasion, and migration of PCa cells decreased dramatically, while PC3 cell apoptosis increased appreciably, accompanied by the suppression of the JNK pathway.

Asymptomatic-anaplasmosis confirmation using genetic and serological tests and possible coinfection with spotted fever group Rickettsia: a case report.

BACKGROUND: Anaplasmosis is an emerging acute febrile disease that is caused by a bite of an Anaplasma phagocytophilum-infected hard tick. As for healthy patients, reports on asymptomatic anaplasmosis resulting from such tick bites are rare. CASE PRESENTATION: A 55-year-old female patient visited the hospital with a tick bite in the right infraclavicular region. The tick was suspected to have been on the patient for more than 10 days. PCR and an indirect immunofluorescence assay (IFA) were performed to identify tick-borne infectious diseases. The blood sample collected at admission yielded a positive result in nested PCR targeting Ehrlichia- or Anaplasma-specific genes groEL and ankA. Subsequent sequencing confirmed the presence of A. phagocytophilum, and seroconversion was confirmed by the IFA involving an A. phagocytophilum antigen slide. PCR detected no Rickettsia-specific genes [outer membrane protein A (ompA) or surface cell antigen 1 (sca1)], but seroconversion of spotted fever group (SFG) rickettsiosis was confirmed by an IFA. CONCLUSIONS: This study genetically and serologically confirmed an asymptomatic A. phagocytophilum infection. Although SFG rickettsiosis was not detected genetically, it was detected serologically. These findings indicate the possibility of an asymptomatic coinfection: anaplasmosis plus SFG rickettsiosis. It is, therefore, crucial for clinicians to be aware of potential asymptomatic anaplasmosis following a tick bite.

First identification of Anaplasma phagocytophilum in both a biting tick Ixodes nipponensis and a patient in Korea: a case report.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum. To date, there have been no reported cases of A. phagocytophilum infection found in both the biting tick and the patient following a tick bite. CASE PRESENTATION: An 81-year-old woman presented with fever following a tick bite, with the tick still intact on her body. The patient was diagnosed with HGA. The tick was identified as Ixodes nipponensis by morphological and molecular biological detection methods targeting the 16S rRNA gene. The patient's blood was cultured after inoculation into the human promyelocytic leukemia cell line HL-60. A. phagocytophilum growth was confirmed via culture and isolation. A. phagocytophilum was identified in both the tick and the patient's blood by Anaplasma-specific groEL- and ankA-based nested polymerase chain reaction followed by sequencing. Moreover, a four-fold elevation in antibodies was observed in the patient's blood. CONCLUSION: We report a case of a patient diagnosed with HGA following admission for fever due to a tick bite. A. phagocytophilum was identified in both the tick and the patient, and A. phagocytophilum was successfully cultured. The present study suggests the need to investigate the possible incrimination of I. nipponensis as a vector for HGA in Korea.

Scalp eschar and neck lymphadenopathy after tick bite (SENLAT) caused by Bartonella henselae in Korea: a case report.

BACKGROUND: Tick-borne lymphadenopathy (TIBOLA) is an infectious disease, mainly caused by species from the spotted fever group rickettsiae and is characterized by enlarged lymph nodes following a tick bite. Among cases of TIBOLA, a case of scalp eschar and neck lymphadenopathy after tick bite (SENLAT) is diagnosed when an eschar is present on the scalp, accompanied by peripheral lymphadenopathy (LAP). Only a few cases of SENLAT caused by Bartonella henselae have been reported. CASE PRESENTATION: A 58-year-old male sought medical advice while suffering from high fever and diarrhea. Three weeks before the visit, he had been hunting a water deer, and upon bringing the deer home discovered a tick on his scalp area. Symptoms occurred one week after hunting, and a lump was palpated on the right neck area 6 days after the onset of symptoms. Physical examination upon presentation confirmed an eschar-like lesion on the right scalp area, and cervical palpation revealed that the lymph nodes on the right side were non-painful and enlarged at 2.5 × 1.5 cm. Fine needle aspiration of the enlarged lymph nodes was performed, and results of nested PCR for the Bartonella internal transcribed spacer (ITS) confirmed B. henselae as the causative agent. CONCLUSION: With an isolated case of SENLAT and a confirmation of B. henselae in Korea, it is pertinent to raise awareness to physicians in other Asian countries that B. henselae could be a causative agent for SENLAT.

Randomized Controlled Trial of the Lateral Push-Off Skater Exercise for High-Intensity Interval Training vs Conventional Treadmill Training.

OBJECTIVE: To examine the therapeutic effects of the lateral push-off skater exercise vs conventional treadmill training on health-related quality of life, cardiorespiratory fitness (CRF), and balance. DESIGN: Single-blinded, randomized controlled trial. SETTING: Outpatient clinic at a tertiary hospital. PARTICIPANTS: Patients after minor stroke (N=36) with National Institutes of Health Stroke Scale scores≤3 between 20 and 65 years of age were randomly assigned to the intervention group (n=18) or the control group (n=18). INTERVENTIONS: Thirty-minute sessions of the skater exercise were performed 3 times weekly for 12 weeks in the intervention group. Conventional treadmill aerobic exercise was conducted in the control group at the same frequency and duration as the experimental group exercise. MAIN OUTCOME MEASURES: The primary outcome was measured using the European Quality of Life-5 Dimension (EQ-5D). Secondary outcomes included CRF and balance indicators. Assessments were performed at baseline (T0), 12 weeks from T0 (T1), and 16 weeks from T0 (T2). RESULTS: Significant improvements in EQ-5D, peak oxygen uptake (VO2peak), peak oxygen pulse, peak minute ventilation (VE), Dynamic Gait Index (DGI), and Berg Balance Scale (BBS) were found in the intervention group after performing the skater exercise (P<.05, all), and these improvements were sustained at T2 (P<.05, all). Between-group comparisons demonstrated greater improvements in EQ-5D, VO2peak, peak oxygen pulse, peak VE, DGI, and BBS in the intervention group than those in the control group at both T1 (P<.05, all) and T2 (P<0.05, all). Correlation analysis showed significant relationships between EQ-5D and VO2peak, peak VE, DGI, and BBS (P<.05, all). CONCLUSIONS: The skater exercise improved health-related quality of life, CRF, and balance in patients after minor stroke more effectively than conventional treadmill-based aerobic exercise. We recommend the skater exercise as a high-intensity interval training program for patients after minor stroke.