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1.
Plant Dis ; 108(8): 2297-2302, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38537143

ABSTRACT

Amaranth (Amaranthus spp. L) is not native to South Korea but is cultivated in small scales for ornamental purposes as well as leafy vegetables and pseudo cereals. In this study, a new species within the genus Fusarium was isolated from amaranth, showing stem rot symptoms from a farmer field in Hwaseong, South Korea. The disease is characterized by dark-brown spots with black borders, leading to withering. Phylogenetic analysis-based concatenated sequences of translation elongation factor 1-alpha (TEF1), beta-tubulin (tub2), calmodulin (cmdA), RNA polymerase largest subunit (RPB1), and RNA polymerase II second largest subunit (RPB2) genes revealed that the obtained isolates formed a distinct clad within the Fusarium fujikuroi species complex and is closely related to F. circinatum. Cultural and morphological characteristics and pathogenicity on healthy amaranth plants (stem and leaves) were examined. The isolates readily differentiated from F. circinatum based on one- to five-septate macroconidia and the absence of sterile hyphae. Based on molecular and morphological characteristics, this fungus is demonstrated to be a new species and is described here as F. amaranthi, the causal agent of stem rot of amaranth in South Korea.


Subject(s)
Amaranthus , Fusarium , Phylogeny , Plant Diseases , Amaranthus/microbiology , Fusarium/genetics , Fusarium/isolation & purification , Fusarium/classification , Plant Diseases/microbiology , Republic of Korea , DNA, Fungal/genetics , Plant Leaves/microbiology , Fungal Proteins/genetics , Plant Stems/microbiology , Sequence Analysis, DNA
2.
Hum Genet ; 142(2): 231-243, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36336746

ABSTRACT

Early-onset acute myocardial infarction (AMI) may have a higher genetic predisposition than late-onset AMI. The present study aimed to identify and characterize germline variants that affect early-onset AMI using whole-genome sequencing (WGS). We performed a genome-wide association study based on the WGS of 1239 Koreans, including 596 early-onset AMI patients and 643 healthy individuals. Patients with AMI who underwent percutaneous coronary intervention (PCI) caused by atherothrombotic occlusive lesions were included in the study. A total of 29 novel loci were found to be associated with early-onset AMI. These loci are involved in thrombosis, fibrinolysis, inflammation, and lipid metabolism. One of the associated single nucleotide variants (SNVs), rs1614576, located upstream of PRKCB, is known to be associated with thrombus formation. Additionally, the results revealed a novel locus, rs78631167, located upstream of PLAUR which plays a critical role in regulating plasminogen activation and is related to fibrinolysis. The association between early-onset AMI and rs9357455, which is located upstream of PHACTR1 and regulates inflammation in AMI, was found. Moreover, we identified a lipid metabolism related genetic risk locus, rs5072, in the APOA1-AS gene. This study provides new evidence supporting the genetic association between early-onset AMI and thrombosis and fibrinolysis, as well as inflammation and lipid metabolism, by analyzing the whole-genome of 596 patients with early-onset AMI who have been treated with PCI. Our findings highlight potential genetic markers for the prediction and management of AMI, as well as for understanding the etiology of AMI.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Thrombosis , Humans , Myocardial Infarction/genetics , Genome-Wide Association Study , Thrombosis/complications , Inflammation , Whole Genome Sequencing
3.
Clin Lab ; 69(5)2023 May 01.
Article in English | MEDLINE | ID: mdl-37145083

ABSTRACT

BACKGROUND: One of the most dangerous side effects of joint replacement for the hip, knee, shoulder, and elbow is prosthesis joint infection (PJI). Polymerase chain reaction (PCR) has been considered a promising method for PJI diagnosis due to its short diagnostic time and high sensitivity. Although several PCR methods such as multiplex PCR and broad-range PCR are useful diagnostic methods for detecting microorganisms causing PJI, values of different PCR methods for the diagnosis of PJI remain unclear. Thus, the objective of this study was to perform a meta-analysis of different PCR methods in the diagnosis of PJI to determine their diagnostic characteristics including sensitivity and specificity. METHODS: The following data were extracted: PCR method, number of patients, sample site and type, diagnosis standard, true positive, false positive, false negative, and true negative. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. Meta-regression analysis was conducted to assess heterogeneity. Subgroup analysis was also performed to assess effects of several variables on meta-analysis results. RESULTS: The current study showed that pooled sensitivity and pooled specificity were 0.70 (95% CI: 0.67 - 0.73) and 0.94 (95% CI: 0.92 - 0.95), respectively. Results of subgroup analysis indicated that sequencing method showed the lowest sensitivity (0.63, 95% CI: 0.59 - 0.67). However, after excluding studies using tissue samples directly, sequencing method showed higher sensitivity (0.83, 95% CI: 0.73 - 0.90) than other PCR methods (0.74, 95% CI: 0.69 - 0.78). CONCLUSIONS: The main significance of this study was that we attempted to classify accuracies of several PCR methods and found that sequencing with a reliable sampling method could be used as an early screening strategy for PJI. Further comparisons for PCR technologies are needed to evaluate their cost effectiveness and diagnostic procedures, not just diagnostic values, to discover the optimal one for PJI diagnosis.


Subject(s)
Arthritis, Infectious , Prostheses and Implants , Humans , Sensitivity and Specificity , Arthritis, Infectious/diagnosis , Multiplex Polymerase Chain Reaction , Odds Ratio , Synovial Fluid
4.
Medicina (Kaunas) ; 59(12)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38138229

ABSTRACT

Background and Objectives: Hip fractures are commonly found in elderly patients, and often result in chronic pain and decreased physical function, as well as worsening of overall health. It is known that early surgical intervention during the acute phase and rehabilitation are important for improving clinical outcomes for these patients. However, the importance of management for improving the quality of life of these patients is becoming more emphasized. Studies on changes in sleep patterns after hip fractures are rare overseas. Therefore, the aim of this study is to investigate the prevalence of sleep disturbance in patients with hip fractures and to analyze the changes in sleep disturbance after surgery by comparing the preoperative and postoperative results. Materials and Methods: During the period from August 2022 to January 2023, patients who underwent surgical treatment for hip fractures and were recruited into the REAL Hip Cohort were selected as research subjects. The sleep survey was conducted using the Pittsburgh Sleep Quality Index (PSQI). The PSQI is composed of 18 questions, each divided into areas of sleep quality, sleep latency, duration, efficiency, disturbance, use of medication, and daytime dysfunction. Each area is scored 0-3 points and the total is 0-21. A score greater than five indicates sleep disorder. The PSQI was surveyed during hospitalization and three months after surgery for post-fracture sleep status. To analyze changes before and after the fracture, paired T-tests and chi-square tests were performed. Results: From August 2022 to January 2023, a total of 40 patients who were recruited into the REAL Hip Cohort responded to the PSQI survey. The average age was 77.4 years and 36 were female. Sleep quality worsened from 0.75 ± 1.0 before surgery to 1.4 ± 1.0 three months after surgery (p = 0.019), and sleep efficiency also worsened from 0.4 ± 0.6 to 1.4 ± 1.0 (p < 0.001). The PSQI increased from an average of 5.2 ± 2.8 before surgery to 8.2 ± 4.2 three months after surgery (p = 0.007), and the number of patients who could be diagnosed with sleep disorders also increased from 12 (40%) to 24 (60%) (p = 0.030). Conclusions: A decline in overall sleep status was observed in patients in a survey on sleep patterns three months after hip fracture. Additional management is needed to improve their sleep patterns.


Subject(s)
Hip Fractures , Sleep Wake Disorders , Humans , Female , Aged , Male , Sleep Quality , Quality of Life , Artificial Intelligence , Hip Fractures/complications , Hip Fractures/epidemiology , Hip Fractures/surgery , Sleep , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology
5.
Sensors (Basel) ; 22(24)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36560254

ABSTRACT

In this study, a noncontact fabric loop sensor based on magnetic-field-induced conductivity, which can simultaneously detect cardiac activity and respiration signals, was developed and the effects of the sensor's shape and measurement position on the sensing performance were analyzed. Fifteen male subjects in their twenties wore sleeveless shirts equipped with various types of fabric loop sensors (spiky, extrusion, and spiral), and the cardiac activity and respiratory signals were measured twice at positions P2, P4, and P6. The measurements were verified by comparing them against the reference electrocardiogram (ECG) and respiratory signals measured using BIOPAC® (MP150, ECG100B, RSP100C). The waveforms of the raw signal measured by the fabric loop sensor were filtered with a bandpass filter (1-20 Hz) and qualitatively compared with the ECG signal obtained from the Ag/AgCI electrode. Notwithstanding a slight difference in performance, the three fabric sensors could simultaneously detect cardiac activity and respiration signals at all measurement positions. In addition, it was verified through statistical analysis that the highest-quality signal was obtained at the measurement position of P4 or P6 using the spiral loop sensor.


Subject(s)
Textiles , Wearable Electronic Devices , Humans , Male , Respiration , Electrodes , Electric Conductivity
6.
Bioorg Chem ; 115: 105167, 2021 10.
Article in English | MEDLINE | ID: mdl-34358800

ABSTRACT

The abnormal self-assembly of amyloid-beta (Aß) peptides into oligomers, as well as insoluble fibrils, has been identified as a key factor for monitoring the progression of Alzheimer's disease (AD). The noninvasive imaging of Aß aggregates utilizing chemical probes can be a powerful and practical technique for accurately diagnosing and monitoring the progress of AD, as well as evaluating the effectiveness of therapeutic drug candidates in treating or managing it. Particularly, the near-infrared (NIR) fluorescence imaging of Aß plaques is a potentially promising approach toward the efficient detection of the biomarker. In this study, we describe a new NIR fluorophore, which was based on curcumin derivatives. The fluorophore is equipped with desirable optical properties for in vivo brain imaging. The emission wavelength of the probe, 8b, is 667 nm, and its fluorescent intensity is significantly increased through binding with the Aß aggregates. The probe allows the clear visualization of the Aß plaques 10 min post administration, and the intensity of the fluorescent signal in the brain of a 5XFAD transgenic mouse model is more than three times higher than that of the normal control group. These results demonstrate that the designed probe can be an effective tool for visualizing Aß plaques, as well as investigating the pathological progress of AD.


Subject(s)
Amyloid beta-Peptides/metabolism , Curcumin/chemistry , Fluorescent Dyes/chemical synthesis , Optical Imaging/methods , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/chemistry , Animals , Binding Sites , Brain/diagnostic imaging , Brain/metabolism , Curcumin/metabolism , Female , Fluorescent Dyes/metabolism , Humans , Mice , Mice, Transgenic , Molecular Docking Simulation , Protein Aggregates , Spectroscopy, Near-Infrared
7.
Int J Med Sci ; 18(5): 1259-1268, 2021.
Article in English | MEDLINE | ID: mdl-33526987

ABSTRACT

Background: Multipotent and immune privileged properties of mesenchymal stem cells (MSCs) were investigated for the treatment of various clinical diseases. For the years, many researches into the animal studies evaluated human stem cell therapeutic capacity related to the regenerative medicine. However, there were limited reports on immune privileged properties of human MSCs in animal studies. The present study investigated hematological and biochemical parameter and lymphocyte subset in mini-pigs following human MSCs transplantation as a means of validation of reliability that influence the animal test results. Methods: The miniature pigs were transplanted with human MSCs seeded with scaffold. After transplantation, all animals were evaluated by CBC, biochemistry and lymphocyte subset test. After 9 weeks, all pigs were sacrificed and organs were histologically analyzed. Results: CBC test showed that levels of RBC were decreased and reticulocyte, WBC and neutrophil were increased in transient state initially after transplantation, but returned to normal value. The proportion of B lymphocyte and cytotoxic T cell were also initially enhanced within the normal range temporarily. The female and male miniature pigs showed normal ranges for blood chemistry assessments. During the 9 weeks post-operative period, the animals showed a continuous increase in body weight and length. Furthermore, no abnormal findings were observed from the histological analysis of sacrificed pigs. Conclusions: Overall, miniature pigs transplanted with human MSCs seeded with scaffold were found to have physiologically similar results to normal animals. This result might be a reliable indicator of the animal experiments using miniature pigs with human MSCs.


Subject(s)
Immune Privilege , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Swine, Miniature/immunology , Animals , Blood Cell Count , Female , Humans , Male , Models, Animal , Regenerative Medicine/methods , Reproducibility of Results , Swine , Tissue Scaffolds , Transplantation, Heterologous
8.
Inflammopharmacology ; 27(6): 1205-1216, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31123968

ABSTRACT

Cilostazol (an inhibitor of phosphodiesterase type III) has potent anti-inflammatory effects, and celecoxib (a COX-2 specific inhibitor) has been reported to improve the unsatisfactory profile of NSAIDs. This study investigated the synergistic anti-arthritic potential of a multitarget-based cotreatment, in which cilostazol was used as an add-on therapy for celecoxib, using the synovial fibroblasts of RA patients (RASFs). Increased COX-2 protein expression and PGE2 synthesis by LPS (1 µg/ml) were significantly and synergistically attenuated by cotreatment with 3 µM cilostazol and 30 µM celecoxib, whereas monotherapy with either cilostazol or celecoxib showed little effects. IL-10 mRNA levels in LPS-treated RASFs were moderately increased by pretreating cilostazol (1-10 µM) or celecoxib (10-50 µM) monotherapy, but 3 µM of cilostazol add-on for 30 µM celecoxib treatment synergistically increased IL-10 mRNA levels and IL-10 release to culture media. Cilostazol and celecoxib cotreatment similarly showed synergistic increase in SOCS3 mRNA levels. Accordingly, LPS-induced increases in IL-1ß and IL-6 mRNA and TNF-α release were significantly and synergistically diminished by cilostazol and celecoxib cotreatment. Moreover, synovial cell proliferation was significantly suppressed by cotreatment. Summarizing, cotreatment with cilostazol and celecoxib exhibited a synergistic increase in IL-10 production and SOCS3 expressions, thereby resulted in synergistic decreases in IL-1ß mRNA, IL-6 mRNA expression and TNF-α synthesis in association with synergistic decreases in COX-2 and PGE2 protein expression in the RA synovial fibroblasts. In conclusion, these observations suggest low concentrations of cilostazol and celecoxib cotreatment may ensure a synergistic anti-arthritic potential.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Celecoxib/pharmacology , Cilostazol/pharmacology , Cytokines/antagonists & inhibitors , Interleukin-10/biosynthesis , Suppressor of Cytokine Signaling 3 Protein/biosynthesis , Synovial Fluid/immunology , Arthritis, Rheumatoid/immunology , Cyclooxygenase 2/genetics , Dinoprostone/biosynthesis , Drug Synergism , Fibroblasts/immunology , Humans , Interleukin-10/genetics , STAT3 Transcription Factor/metabolism , Suppressor of Cytokine Signaling 3 Protein/genetics , Synovial Fluid/cytology
9.
Mol Pharmacol ; 94(6): 1401-1411, 2018 12.
Article in English | MEDLINE | ID: mdl-30366981

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is an increasingly studied condition that can progress to end-stage liver disease. Although NAFLD was first described in 1980, a complete understanding of the mechanism and causes of this disease is still lacking. Six-transmembrane protein of prostate 2 (STAMP2) plays a role in integrating inflammatory and nutritional signals with metabolism. Our previous study suggested that STAMP2 may be a suitable target for treating NAFLD. In the current study, we performed a focused drug-screening and found that cilostazol could be a potential STAMP2 enhancer. Thus, we examined whether cilostazol alleviates NAFLD through STAMP2. The in vivo and in vitro pharmacological efficacies of cilostazol on STAMP2 expression and lipid accumulation were analyzed in NAFLD mice induced by high-fat diet (HFD) and in HepG2 cell lines treated by oleic acid (OA), respectively. Cilostazol increased the expression of STAMP2 through transcriptional regulation in vivo and in vitro. Cilostazol also dampened the STAMP2 downregulation caused by the HFD and by OA in vivo and in vitro, respectively. Cilostazol activated AMP-activated protein kinase (AMPK) in vivo and in vitro, and AMPK functions upstream of STAMP2, and reversed downregulation of STAMP2 expression through AMPK in the NAFLD model. Cilostazol ameliorates hepatic steatosis by enhancing hepatic STAMP2 expression through AMPK. Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD.


Subject(s)
Cilostazol/pharmacology , Diet, High-Fat/adverse effects , Fatty Liver/drug therapy , Liver/drug effects , Membrane Proteins/genetics , Up-Regulation/genetics , AMP-Activated Protein Kinases/genetics , Animals , Cell Line, Tumor , Down-Regulation/drug effects , Down-Regulation/genetics , Fatty Liver/genetics , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Hep G2 Cells , Humans , Lipid Metabolism/drug effects , Lipid Metabolism/genetics , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/genetics , Transcription, Genetic/drug effects , Transcription, Genetic/genetics , Up-Regulation/drug effects
10.
Biochem Biophys Res Commun ; 503(3): 1260-1266, 2018 09 10.
Article in English | MEDLINE | ID: mdl-30005874

ABSTRACT

Free fatty acids (FFAs) are considered the principal inducers of lipotoxicity, leading to cell dysfunction and/or cell death. Lipotoxicity in Schwann cells (SCs) damages neurons, which may be associated with peripheral neuropathies and axon degeneration. However, the molecular mechanism by which FFAs exert lipotoxicity in SCs remains to be established. In the present study, we demonstrate that palmitate exerts lipotoxicity in SCs through apoptosis and that palmitate-induced lipotoxicity in SCs is mediated through reactive oxygen species (ROS) generation. We observed that the six-transmembrane protein of prostate 2 (STAMP2), which plays a pivotal role in lipid homeostasis, is expressed in SCs. We further demonstrate that palmitate induces lipoapoptosis in SCs through ROS generation-mediated STAMP2 downregulation and that STAMP2 depletion accelerates the palmitate-exerted lipoapoptosis in SCs, indicating that STAMP2 confers on SCs the ability to resist palmitate-induced lipotoxicity. In conclusion, palmitate induces lipoapoptosis in SCs through ROS generation-mediated STAMP2 downregulation. Our findings indicate that ROS and STAMP2 may represent suitable targets for pharmacological interventions targeting lipotoxicity-associated peripheral neuropathies and axon degeneration.


Subject(s)
Apoptosis/drug effects , Down-Regulation/drug effects , Oxidoreductases/deficiency , Palmitates/pharmacology , Reactive Oxygen Species/metabolism , Schwann Cells/drug effects , Schwann Cells/pathology , Animals , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Oxidoreductases/genetics , Oxidoreductases/metabolism , Rats , Schwann Cells/metabolism , Structure-Activity Relationship
11.
Biochim Biophys Acta ; 1852(10 Pt A): 2137-44, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26170060

ABSTRACT

Osteoclasts are bone-specific multinucleated cells generated by differentiation of monocyte/macrophage hematopoietic lineages and degrade bone matrix by secretion of lytic enzymes. The regulation of osteoclast differentiation provides a potential strategy for treatment of bone-lytic damage. In this study, cilostazol, an inhibitor of type III phosphodiesterase, inhibited RANKL [receptor activator of nuclear factor kappa B (RANK) ligand]-induced RANK expression in bone marrow-derived monocyte/macrophage precursors (BMMs) and Raw 264.7 cells by inhibiting PU.1 via SIRT1 activation. RANKL-induced RANK expression was attenuated by cilostazol and rSIRT1 in Raw 264.7 cells, and these were blocked by sirtinol. In line with these, cilostazol elevated SIRT1 mRNA and protein levels in 12-24h and increased SIRT1 activity, and these effects were inhibited by sirtinol. Furthermore, the RANKL-induced nuclear expression of PU.1, a transcription factor required for macrophage differentiation, was suppressed by cilostazol. Additionally, marked RANKL-induced RANK immunofluorescence staining in Raw 264.7 cells was attenuated by cilostazol and rSIRT1, and both attenuations were prevented by sirtinol. Extensive RANK staining of knee synovial tissues in a mouse model of collagen-induced arthritis (CIA) was markedly reduced by cilostazol (30mg/kg/day). In line with these results, both RANKL- and M-CSF-induced differentiation of BMMs to multinucleated TRAP(+) giant cells and resorption pit formation were inhibited by cilostazol associated with a decrease in TRAP (a marker enzyme of osteoclasts) activity. In conclusion, cilostazol activates SIRT1, which suppresses the nuclear translocation of PU.1, and thus, inhibits RANKL-stimulated RANK expression and causes anti-osteoclast formation in BMMs in vitro and in their murine model of CIA.

12.
Rheumatol Int ; 35(5): 861-9, 2015 May.
Article in English | MEDLINE | ID: mdl-25315702

ABSTRACT

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures.


Subject(s)
Brain/pathology , Lupus Vasculitis, Central Nervous System/pathology , Adolescent , Adult , Aged , Atrophy , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/pathology , Child , Cognition Disorders/etiology , Cognition Disorders/pathology , Cohort Studies , Confusion/etiology , Confusion/pathology , Cranial Nerve Diseases/etiology , Cranial Nerve Diseases/pathology , Diffusion Magnetic Resonance Imaging , Female , Gray Matter/pathology , Headache/etiology , Headache/pathology , Humans , Lupus Vasculitis, Central Nervous System/complications , Lupus Vasculitis, Central Nervous System/psychology , Magnetic Resonance Imaging , Male , Middle Aged , Psychotic Disorders/etiology , Psychotic Disorders/pathology , Retrospective Studies , Seizures/etiology , Seizures/pathology , White Matter/pathology , Young Adult
13.
Toxicol Appl Pharmacol ; 266(1): 9-18, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23147571

ABSTRACT

Previous studies have reported that a Gamitrinib variant containing triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits its activity, thus inducing the apoptotic pathway in the cells. Accordingly, G-TPP shows a potential as a promising drug for the treatment of cancer. A cell can die from different types of cell death such as apoptosis, necrosis, necroptosis, and autophagic cell death. In this study, we further investigated the mechanisms and modes of cell death in the G-TPP-treated Hep3B and U937 cell lines. We discovered that G-TPP kills the U937 cells through the apoptotic pathway and the overexpression of Bcl-2 significantly inhibits U937 cell death to G-TPP. We further discovered that G-TPP kills the Hep3B cells by activating necroptosis in combination with the partial activation of caspase-dependent apoptosis. Importantly, G-TPP overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. We also observed that G-TPP induces compensatory autophagy in the Hep3B cell line. We further found that whereas there is a Bcl-2-Beclin 1 interaction in response to G-TPP, silencing the beclin 1 gene failed to block LC3-II accumulation in the Hep3B cells, indicating that G-TPP triggers Beclin 1-independent protective autophagy in Hep3B cells. Taken together, these data reveal that G-TPP induces cell death through a combination of death pathways, including necroptosis and apoptosis, and overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. These findings are important for the therapeutic exploitation of necroptosis as an alternative cell death program to bypass the resistance to apoptosis.


Subject(s)
Apoptosis/physiology , Guanidines/administration & dosage , HSP90 Heat-Shock Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/metabolism , Lactams, Macrocyclic/administration & dosage , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Apoptosis/drug effects , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Drug Delivery Systems/methods , Guanidines/chemistry , Humans , Lactams, Macrocyclic/chemistry , Mitochondria/drug effects , Mitochondria/pathology , Necrosis , U937 Cells
14.
Clin Orthop Surg ; 15(4): 552-559, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37529188

ABSTRACT

Background: Teriparatide is an effective anabolic agent used in the treatment of severe osteoporosis. In addition, it is also used to promote fracture healing. The purpose of this double-blind randomized controlled trial was to evaluate the influence of weekly teriparatide administration on bone formation in hip fracture patients. Methods: The control group (n = 41) was composed of patients treated with normal saline other than teriparatide, and the teriparatide group (n = 51) consisted of patients who received weekly teriparatide. Bone turnover markers, C-terminal telopeptide (CTx) and osteocalcin (OC), were assessed through blood tests at the initial hospital visit and 3-month, 6-month, and 1-year follow-ups. Dual-energy X-ray absorptiometry was performed 5 days postoperatively and at 1-year postoperative follow-up. The degree of fracture union was evaluated by comparing the radiographic union scoring system for hips using Radiographic Union Score for Hip (RUSH) scores between the two groups at 3 months, 6 months, and 1 year after surgery. Results: Evaluation of the rate of change in bone mineral density over 1 year showed that the lumber bone mineral density increased by more than 7% in the experimental group. The control group did not show a difference between the CTx and OC at 6 months, but the difference between the CTx and OC values was large at 6 months in the experimental group. The mean RUSH score was significantly different between the control group and the experimental group: 12.105 and 15.476, respectively (p = 0.004), at 3 months and 18.571 and 22.389, respectively, at 6 months (p = 0.006). Conclusions: Weekly use of teriparatide improved fracture healing, bone formation, and clinical outcomes at 1 year after hip fracture surgery by the anabolic window effect.


Subject(s)
Bone Density Conservation Agents , Hip Fractures , Osteoporosis, Postmenopausal , Female , Humans , Teriparatide/therapeutic use , Bone Density Conservation Agents/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/chemically induced , Postmenopause , Hip Fractures/drug therapy , Hip Fractures/surgery , Bone Density
15.
Clin Interv Aging ; 18: 1021-1035, 2023.
Article in English | MEDLINE | ID: mdl-37427010

ABSTRACT

Objective: The world population gradually getting older, age-related sarcopenia is becoming more frequent. Known to be highly prevalent in high income countries, relative data in Africa are still scarce. This review aims to estimate the prevalence of sarcopenia in Africa and its characteristics. Study Design and Setting: A literature search in PubMed, Web of Science, Google Scholar, and Scopus was conducted in October 2022. All studies reporting the prevalence of sarcopenia in Africa within 15 years were included, and we did an assessment of bias with Hoy et al's risk bias assessment tool. The estimated prevalence of sarcopenia was the outcome and we performed secondary analyses by age, gender, and diagnostic criteria. The random effect model was used for the prevalence estimation. The prevalence of sarcopenia and 95% confidence interval (95% CI) were calculated using the inverse-variance method. Results: A total of 17 studies met our eligibility criteria, for a study population of 12,690 participants with 44.3% males and 55.7% females. The overall prevalence of sarcopenia was 25% (95% CI: 19-30%). The prevalence of sarcopenia among 50 years old and older was 23% (95% CI: 17-29%). We had a higher prevalence of sarcopenia among males (30%, %95 IC: 20-39%) than females (29%, %95 IC: 21-36%). The prevalence of sarcopenia was different depending on the diagnosis criteria used. Conclusion: The prevalence of sarcopenia in Africa was relatively high. However, the fact that the majority of included studies were hospital-based studies shows the necessity of further community-based studies in order to have a more accurate representation of the situation in the general population.


Subject(s)
Sarcopenia , Male , Female , Humans , Sarcopenia/epidemiology , Sarcopenia/diagnosis , Prevalence , Africa/epidemiology
16.
Musculoskelet Sci Pract ; 66: 102808, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37352763

ABSTRACT

BACKGROUND: Because disability in Osteoarthritis (OA) may change physical activity (PA), which might affect the disease progression, it is important to measure a patient's daily PA to study the relationship between a patient's PA and disease progression. OBJECTIVE: The objective of the present study was to investigate the relationship between PA and patients with OA and people without OA using data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: Demographic study was conducted to obtain data of comorbidities of participants. PA was compared between the group with OA (OA group) and the group without OA (non-OA group). In addition, PAs of OA patients with comorbidities and those without comorbidities were compared. The cut-off of moderate to vigorous physical activity (MVPA) was obtained through a receiver operating characteristic (ROC) curve. RESULTS: In the demographic study, there were significantly more educated participants in the OA group (p < .001). Actigraph data showed a significant decrease in MVPA (p < .001) but a significant increase in light activity (p = .002) in the OA group. In addition, the OA group showed significantly lower light PA but significantly higher MVPA in ≥10 min bout length. OA patients with comorbidities showed higher MVPA than OA patients without comorbidities (p = .044). The cut-off point of MVPA was 7.071 min/day when ROC curve was conducted. CONCLUSIONS: The present study suggests that patients with OA and low activity need a certain level of physical activity and a cut-off point for MVPA is presented which accounts for comorbidities in OA patients.


Subject(s)
Exercise , Osteoarthritis , Humans , Aged , Nutrition Surveys , Motor Activity , Accelerometry
17.
Plants (Basel) ; 12(8)2023 Apr 10.
Article in English | MEDLINE | ID: mdl-37111837

ABSTRACT

This study aimed to investigate the effect of light [a long-day photoperiod (16 h light/8 h dark cycle)] and dark treatment on the production of rosmarinic acid in P. frutescens microgreens and to determine its antioxidant and antibacterial activities. Microgreens of P. frutescens were grown under light and dark conditions and harvested after 10, 15, 20, and 25 days of each treatment. Although dry weight values of microgreens gradually increased from 10 to 25 days of both treatments, the microgreens grown under light treatment possessed slightly higher levels of dry weight than those grown in the dark. Rosmarinic acid and total phenolic content (TPC) were also analyzed using high-performance liquid chromatography (HPLC) and Folin-Ciocalteu assay. The accumulation patterns of rosmarinic acid and TPC gradually increased and decreased, respectively, in P. frutescens microgreens grown in continuous darkness. The highest accumulation was observed in microgreens grown for 20 days. However, rosmarinic acid and TPC values were not significantly different in microgreens grown under light conditions. According to the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition assay, the extracts of P. frutescens microgreens were confirmed to be strong antioxidants, and their ability to scavenge DPPH radicals was positively correlated with the total phenolic content in the microgreens after 10, 15, 20, and 25 days of both treatments. Considering the relatively higher values of dry weight, rosmarinic acid, TPC, and DPPH assay, P. frutescens microgreens after 20 days of darkness and 20 days of light treatment, respectively, were selected for screening antibacterial activity using nine pathogens. Both microgreen extracts showed strong antibacterial activity against pathogens. In particular, the extracts of microgreens grown for 20 days under light treatment showed higher antimicrobial effects. Therefore, the light treatments for 20 days, as well as the darkness treatment for 20 days, were the best conditions for P. frutescens microgreen production because of their high levels of dry weight, phenolics, and biological activities.

18.
BMC Genom Data ; 24(1): 48, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37653517

ABSTRACT

BACKGROUND: Sarcopenia is a disease diagnosed in the elderly. In patients with sarcopenia, the muscle mass decreases every year. The occurrence of sarcopenia is greatly affected by extrinsic factors such as eating habits, exercise, and lifestyle. The present study aimed to determine the relationship between muscle mass traits and genes affected by epigenetic factors with three different adjustment methods using Korean Genome and Epidemiology Study (KOGES) data. RESULTS: We conducted a demographic study and DNA methylation profiling by three studies according to the muscle mass index (MMI) adjustment methods: appendicular skeletal muscle mass divided by body weight (MMI1); appendicular skeletal muscle mass divided by square of height (MMI2); appendicular skeletal muscle mass divided by BMI (MMI3). We analyzed differentially methylated regions (DMRs) for each group. We then restricted our subjects to be top 30% (T30) and bottom 30% (B30) based on each MMI adjustment method. Additionally, we performed enrichment analysis using PathfindR to evaluate the relationship between identified DMRs and sarcopenia. A total of 895 subjects were included in the demographic study. The values of BMI, waist, and hip showed a significant difference in all three groups. Among 446 participants, 44 subjects whose DNA methylation profiles were investigated were included for DNA methylation analysis. The results of enrichment analysis showed differences between groups. In the women group through MMI1 method, only the glutamatergic synapse pathway showed a significant result. In the men group through MMI2 method, the adherens junction pathway was the most significant. Women group through MMI2 method showed similar results, having an enriched Rap1 signaling pathway. In men group through MMI3 method, the Fc epsilon RI signaling pathway was the most enriched. Particularly, the notch signaling pathway was significantly enriched in women group through MMI3 method. CONCLUSION: This study presents results about which factor should be concerned first in muscle mass index (MMI) adjustment. The present study suggested that GAB2 and JPH3 in MMI1 method, HLA-DQB1 and TBCD in MMI2 method, GAB2, NDUFB4 and ISPD in MMI3 method are potential genes that can have an impact on muscle mass. It could enable future epigenetic studies of genes based on annotation results. The present study is a nationwide study in Korea with the largest size up to date that compares adjustment indices for MMI in epigenetic research.


Subject(s)
DNA Methylation , Sarcopenia , Aged , Female , Humans , Male , Adherens Junctions , DNA Methylation/genetics , Microtubule-Associated Proteins , Muscle, Skeletal , Sarcopenia/epidemiology , Sarcopenia/genetics
19.
J Bone Metab ; 30(3): 245-252, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37718902

ABSTRACT

BACKGROUND: Dual energy X-ray absorptiometry (DXA) is a preferred modality for screening or diagnosis of osteoporosis and can predict the risk of hip fracture. However, the DXA test is difficult to implement easily in some developing countries, and fractures have been observed before patients underwent DXA. The purpose of this systematic review is to search for studies that predict the risk of hip fracture using artificial intelligence (AI) or machine learning, organize the results of each study, and analyze the usefulness of this technology. METHODS: The PubMed, OVID Medline, Cochrane Collaboration Library, Web of Science, EMBASE, and AHRQ databases were searched including "hip fractures" AND "artificial intelligence". RESULTS: A total of 7 studies are included in this study. The total number of subjects included in the 7 studies was 330,099. There were 3 studies that included only women, and 4 studies included both men and women. One study conducted AI training after 1:1 matching between fractured and non-fractured patients. The area under the curve of AI prediction model for hip fracture risk was 0.39 to 0.96. The accuracy of AI prediction model for hip fracture risk was 70.26% to 90%. CONCLUSIONS: We believe that predicting the risk of hip fracture by the AI model will help select patients with high fracture risk among osteoporosis patients. However, to apply the AI model to the prediction of hip fracture risk in clinical situations, it is necessary to identify the characteristics of the dataset and AI model and use it after performing appropriate validation.

20.
J Bone Metab ; 30(3): 263-273, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37718904

ABSTRACT

BACKGROUND: The purpose of this study was to verify the accuracy and validity of using machine learning (ML) to select risk factors, to discriminate differences in feature selection by ML between men and women, and to develop predictive models for patients with osteoporosis in a big database. METHODS: The data on 968 observed features from a total of 3,484 the Korea National Health and Nutrition Examination Survey participants were collected. To find preliminary features that were well-related to osteoporosis, logistic regression, random forest, gradient boosting, adaptive boosting, and support vector machine were used. RESULTS: In osteoporosis feature selection by 5 ML models in this study, the most selected variables as risk factors in men and women were body mass index, monthly alcohol consumption, and dietary surveys. However, differences between men and women in osteoporosis feature selection by ML models were age, smoking, and blood glucose level. The receiver operating characteristic (ROC) analysis revealed that the area under the ROC curve for each ML model was not significantly different for either gender. CONCLUSIONS: ML performed a feature selection of osteoporosis, considering hidden differences between men and women. The present study considers the preprocessing of input data and the feature selection process as well as the ML technique to be important factors for the accuracy of the osteoporosis prediction model.

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