Leaves and pseudostems extract of Curcuma longa attenuates immunoglobulin E/bovine serum albumin-stimulated bone marrow-derived cultured mast cell activation and passive cutaneous anaphylaxis in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa, known as turmeric, is an herbaceous perennial plant belonging to the genus Curcuma. It is dispersed throughout tropical and subtropical regions worldwide. Since ancient times, turmeric has been used as an ethnomedicinal plant in the Ayurvedic system, particularly in Asian countries. Rhizomes of turmeric possess several pharmacological properties that give high value as a medicinal remedy for treating a range of conditions, including inflammation, pain, allergies, and digestive issues. Moreover, turmeric leaves and pseudostems also contain a variety of health-enhancing secondary metabolites, such as curcumin, flavonoids, and other phenolic compounds, which exhibit anti-inflammatory, antitumor, antibacterial, and antioxidant properties. AIM OF THE STUDY: Allergic diseases are a group of immune-mediated disorders mainly caused by an immunoglobulin E (IgE)-dependent immunological response to an innocuous allergen. Therefore, this study aimed to investigate the effect of leaves and pseudostems extract of turmeric (TLSWE-8510) on IgE/bovine serum albumin (BSA)-stimulated allergic responses in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. MATERIALS AND METHODS: The effect of TLSWE-8510 on mast cell degranulation has been evaluated by investigating the release of ß-hexosaminidase and histamine in IgE/BSA-stimulated BMCMCs. Additionally, anti-allergic properties of TLSWE-8510 on IgE/BSA-stimulated BMCMCs were investigated using suppression of nuclear factor-kappa B (NF-κB), and spleen tyrosine kinase (Syk)-linker for T-cell activation (LAT)-extracellular-signal-regulated kinase (ERK)-GRB2 associated binding protein 2 (Gab2) signaling pathway and downregulation of allergy-related cytokines and chemokines expression. Furthermore, in vivo, studies were conducted using IgE-mediated PCA in BALB/c mice. RESULTS: TLSWE-8510 treatment significantly inhibited the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine dose-dependently. Additionally, TLSWE-8510 reduced the expression of high-affinity IgE receptors (Fc epsilon receptor I-FcεRI) on the surface of BMCMCs and the binding of IgE to FcεRI. Besides, the expression of cytokines and chemokines is triggered by IgE/BSA stimulation via activating the allergy-related signaling pathways. TLSWE-8510 dose-dependently downregulated the mRNA expression and the production of allergy-related cytokines (interleukin (IL)-1ß, IL-3, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ), and chemokines (thymus and activation-regulated chemokine (TARC), and regulated upon activation, normal T cell expressed and secreted (RANTES)) by regulating the phosphorylation of downstream signaling molecules, NF-κB, and Syk, LAT, ERK and Gab2 in IgE/BSA-stimulated BMCMCs. Moreover, PCA reaction in IgE/BSA-stimulated BALB/c mice ears was effectively decreased by TLSWE-8510 treatment in a dose-dependent manner. CONCLUSIONS: These results collectively demonstrated that TLSWE-8510 suppressed mast cell degranulation by inhibiting the release of chemical mediators related to allergies. TLSWE-8510 downregulated the allergy-related cytokines and chemokines expression and phosphorylation of downstream signaling molecules in IgE/BSA-stimulated BMCMCs. Furthermore, in vivo studies with IgE-mediated PCA reaction in the BALB/c mice ears were attenuated by TLSWE-8510 treatment. These findings revealed that TLSWE-8510 has the potential as a therapeutic agent for the treatment of allergic diseases.

Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study.

Although remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety and efficacy during bronchoscopy are limited. This study aimed to compare the safety and efficacy of remimazolam with those of midazolam for bronchoscopy. This prospective randomized parallel-group study was conducted at a single institution. The primary outcome was the time from the end of the procedure to full alertness. Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated. The time taken to reach peak sedation and the time from the end of the procedure to full alertness was significantly shorter in the remimazolam group than in the midazolam group (median [interquartile range], 2 min [1-4] vs. 3 min [2-5], P = 0.006; and median, 2 min [1-5] vs. 5 min [1-12], P = 0.035, respectively). In patients with non-biopsy procedures (n = 79), participant satisfaction was significantly higher in the remimazolam group than in the midazolam group (median rated scale, 10 vs. 7, P = 0.042). Physician satisfaction and willingness to repeat the procedure were similar between groups. Although the incidence of adverse effects was similar between the groups and there was no significant difference, the midazolam group had a higher antidote administration rate than the remimazolam group (15.7% vs. 4.1%, P = 0.092). Remimazolam is effective and safe for achieving adequate sedation, with a shorter onset time and faster neuropsychiatric recovery than midazolam. It may be a new option for sedation during bronchoscopy.Trial registration: The trial registration number is NCT05994547, and the date of first registration is 16/08/2023.

Effectiveness of the use of an oscillating positive expiratory pressure device in bronchiectasis with frequent exacerbations: a single-arm pilot study.

Impaired airway clearance in patients with non-cystic fibrosis bronchiectasis causes frequent bacterial infection, chronic inflammation, and progressive tissue destruction. We aimed to evaluate whether an oscillating positive expiratory pressure (OPEP) device could allow effective sputum expectoration and prevent acute exacerbations in patients with bronchiectasis who had frequent acute exacerbations. This open-label, single-arm, prospective study included 17 patients who experienced three or more acute exacerbations in the past year. We evaluated the prevention of acute exacerbations, subjective symptom improvement, and change in sputum amount during the use of the Aerobika (Trudell Medical International, London, ON) OPEP device twice daily for 6 months. Of all enrolled patients, only two acute exacerbations occurred during the study period, indicating a significant decrease compared with the number of acute exacerbations before the device use (p < 0.001). Additionally, Bronchiectasis Health Questionnaire score changed from 58.7 to 66.6, showing significant improvement over the treatment period (p < 0.001). The largest sputum volume was observed 3 months after OPEP device use (baseline: 10 ml, 3rd month 25 ml, p = 0.325). There were no major adverse events related to the use of OPEP devices. Twice-daily physiotherapy with OPEP device in patients with bronchiectasis who have frequent exacerbations may facilitate symptomatic improvement and prevention of acute exacerbations without serious adverse events.

Multidisciplinary team approach on tracheoesophageal fistula in a patient with home ventilator.

A 68-year-old man was transferred to our tertiary hospital. Ten years ago, he received radiation therapy for tonsil cancer, and while there was no evidence of recurrence, he suffered from recurrent aspiration. We treated his aspiration pneumonia in the intensive care unit. Prior to his discharge, he received percutaneous dilatational tracheostomy (PDT) before he was transferred to a nursing hospital. Nine months later, he was readmitted owing to tracheoesophageal fistula (TEF). However, he was considered unsuitable for conservative intervention after a multidisciplinary team discussion. Esophageal stent insertion was impossible due to the high level of TEF in the esophagus. Additionally, the size of the TEF could not be covered by an endosponge and endoluminal vacuum therapy, and there was no tracheal stent that could cover his large trachea. The preceding percutaneous enteral gastrostomy (PEG) procedure was required for the primary closure operation of the esophagus; however, family's consent could not be obtained. After 1month, the patient and his family changed their minds and agreed to the procedure and we attempted to perform PEG procedure. However, we could not proceed with PEG owing to stenosis in the inlet of the esophagus. Then, the patient deteriorated clinically and died due to pneumonia with septic shock.

Clinical characteristics, radiological features, and disease severity of bronchiectasis according to the spirometric pattern.

Bronchiectasis show various ventilatory disorders in pulmonary function. The characteristics and severity of patients with bronchiectasis according to these pulmonary dysfunctions are still very limited. This study aimed to evaluate the clinical, radiologic feature and the disease severity of patients with bronchiectasis according to spirometric patterns. We retrospectively evaluated 506 patients with bronchiectasis who underwent pulmonary lung function test (PFT) at a referral hospital between 2014 to 2021. The results showed that cylindrical type was the most common (70.8%) type of bronchiectasis on chest Computed tomography (CT), and 70% of patients had bilateral lung involvement. On the other hand, obstructive ventilatory disorder was the most common (51.6%), followed by normal ventilation (30%) and restrictive ventilatory disorder (18.4%). The modified Medical Research Council (mMRC) was highest in patients with obstructive ventilatory disorders, Modified Reiff score [median (interquartile range)] [6 (3-10), P < 0.001], FACED (FEV1, Age, Chronic colonization, Extension, and Dyspnea) score [3 (1-4), P < 0.001], and Bronchiectasis Severity (BSI) score [8 (5-11), P < 0.001] showed significantly highest values of obstructive ventilatory disorder rather than restrictive ventilatory disorder and normal ventilation. More than half of patients with bronchiectasis had obstructive ventilatory disorder. Bronchiectasis with obstructive ventilatory disorders has more dyspnea symptom, more disease severity and more radiologic severity. There was no significant association between spirometric pattern and radiologic type, but the more severe the radiologic severity, the more severe the lung function impairment.

Clinical profiles and outcomes of pulmonary tuberculosis patients with delayed treatment at a tertiary hospital in South Korea.

BACKGROUND: Data on the clinical characteristics of delayed treatment initiation among pulmonary tuberculosis (TB) patients are lacking. Thus, this study aimed to identify the factors associated with delayed treatment in culture-confirmed pulmonary TB and to assess outcomes of delayed treatment. METHODS: We retrospectively evaluated 151 patients with culture-confirmed pulmonary TB between 2015 and 2017. Delayed and timely treatment was defined as initiation of anti-TB treatment after and before the identification of Mycobacterium tuberculosis complex isolate, respectively. Factors related to delayed treatment, such as comorbidities, clinical presentation, and patterns of initial healthcare use, were collected. We analyzed whether delayed treatment was associated with all-cause mortality using a multivariate binary logistic regression model adjusted for age, sex, cardiovascular disease, and malignancy. RESULTS: In total, 55 (36.4%) patients had delayed treatment. The median length between the first medical visit and treatment initiation was 9 days. Compared with timely treatment, delayed treatment was associated with no initial visit to a non-pulmonary department [adjusted odds ratio (aOR) =10.49, 95% confidence interval (CI), 2.56-42.93] and absence of nucleic acid amplification test (aOR =7.54, 95% CI, 2.75-20.67). After adjusting for age, sex, cardiovascular disease, and solid malignancies, delayed treatment was significantly associated with all-cause mortality (aOR =3.79, 95% CI, 1.36-10.58). The most frequent possible cause of delayed treatment was the doctor's low suspicion of active TB disease. CONCLUSIONS: Given that delayed treatment is associated with worse outcomes in South Korea, targeted interventions to increase awareness on TB in the healthcare community are necessary for additional mycobacterial tests and consults of suspicious patients to TB specialists.

High prevalence of physical inactivity after heart valve surgery and its association with long-term mortality: A nationwide cohort study.

AIMS: Physical activity (PA) and systematic efforts, such as cardiac rehabilitation, are recommended by several national guidelines for those who have received heart valve surgery. However, only a few studies have demonstrated real-world situations, such as changes in the PA level after heart valve surgery, and their effects on long-term outcomes. We designed this study to investigate the changes in PA after heart valve surgery and their associations with mortality using nationwide representative data. METHODS: This study was performed using the Korean National Health Insurance Service database. We included patients who received heart valve surgery from 2009 to 2015 and underwent regular health checkups before and after surgery. Subjects were grouped according to their PA level before and after the surgery. Information on all-cause mortality was obtained until 31 December 2016, with a maximum follow-up period of 5 years. RESULTS: Of the 6587 subjects, 3258 (49.5%) were physically inactive after surgery. Among patients who were physically active (n = 3070), 1196 (39.0%) became inactive after surgery. The postoperative 'inactive' group showed higher mortality than the 'active' group (hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.08-1.83). The 'inactive/inactive' group showed the highest risk of mortality (HR: 1.69, 95% CI: 1.19-2.40) compared with the 'active/active' group. CONCLUSIONS: Insufficient PA level after heart valve surgery is associated with higher risk of mortality. However, maintaining sufficient PA after heart valve surgery may be challenging for many patients. Therefore, systematic efforts, such as cardiac rehabilitation, should be considered in those who received heart valve surgery.

Clinical T category for lung cancer staging: A pragmatic approach for real-world practice.

BACKGROUND: To determine which components should be measured and which window settings are appropriate for computerized tomography (CT) size measurements of lung adenocarcinoma (ADC) and to explore interobserver agreement and accuracy according to the eighth edition of TNM staging. METHODS: A total of 165 patients with surgically resected lung ADC earlier than stage 3A were included in this study. One radiologist and two pulmonologists independently measured the total and solid sizes of components of tumors on different window settings and assessed solidity. CT measurements were compared with pathologic size measurements. RESULTS: In categorizing solidity, 25% of the cases showed discordant results among observers. Measuring the total size of a lung adenocarcinoma predicted pathologic invasive components to a degree similar to measuring the solid component. Lung windows were more accurate (intraclass correlation [ICC] = 0.65-0.81) than mediastinal windows (ICC = 0.20-0.72) at predicting pathologic invasive components, especially in a part-solid nodule. Interobserver agreements for measurement of solid components were good with little significant difference (lung windows, ICC = 0.89; mediastinal windows, ICC = 0.91). A high level of interobserver agreement was seen between the radiologist and pulmonologists and between residents (from the division of pulmonology and critical care) versus a fellow (from the division of pulmonology and critical care) on different windows. CONCLUSIONS: A considerable percentage (25%) of discrepancies was encountered in categorizing the solidity of lesions, which may decrease the accuracy of measurements. Lung window settings may be superior to mediastinal windows for measuring lung ADCs, with comparable interobserver agreement and moderate accuracy for predicting pathologic invasive components. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Lung window settings are better for evaluating part-solid lung adenocarcinoma (ADC), with comparable interobserver agreement and moderate accuracy for predicting pathologic invasive components. The considerable percentage (25%) of discrepancies in categorizing solidity of the lesions may also have decreased the accuracy of measurements. WHAT THIS STUDY ADDS: For accurate measurement and categorization of lung ADC, robust quantitative analysis is needed rather than a simple visual assessment.

The use of surgery in a real-world clinic to diagnose and treat pulmonary cryptococcosis in immunocompetent patients.

BACKGROUND: We evaluated the role played by surgery in the diagnosis and treatment of pulmonary cryptococcosis (PC) in immunocompetent subjects. METHODS: We retrospectively studied 53 immunocompetent patients who were pathologically diagnosed with PC between January 2000 and December 2016 in a tertiary referral center. We compared the radiological presentations of, and diagnostic modalities used to evaluate, patients diagnosed both surgically and non-surgically. We also compared the treatment outcomes of patients who underwent surgical resection alone and those who received additional antifungals following surgical resection. RESULTS: Of the 53 patients, 30 (57%) were diagnosed via non-surgical modalities including percutaneous needle biopsy (PCNB) (n=29) and transbronchial lung biopsy (TBLB) (n=1); and 23 (43%) were diagnosed by surgical modalities including video-assisted thoracoscopic wedge resection (n=22) and lobectomy (n=1). An initial clinical suspicion of a lung malignancy was associated with the use of surgical diagnostic approaches (P<0.001). Whereas undetermined locations were associated with the use of surgical diagnostic approaches, radiological findings such as clustered nodular patterns (P<0.001), cavities (P=0.005), air bronchograms (P<0.001), and peripheral lesions (P<0.001) were associated with the use of non-surgical diagnostic approaches. Of the 30 non-surgically diagnosed patients, 21 (70%) were treated with antifungals and 9 (30%) were followed-up without treatment. Of the 23 patients who underwent surgical treatment, 8 received additional antifungals. The proportion of patients who had radiological improvement was significantly higher in surgically diagnosed patients than non-surgically diagnosed patients (100% vs. 73%; P=0.007). However, there was no significant difference in disease progression between patients who underwent surgical resection alone and those who additionally received antifungals (P=0.999). CONCLUSIONS: Surgical resection was required in some patients to diagnose PC. An initial suspicion of a lung malignancy was associated with use of surgical diagnostic approaches. Surgical resection not only afforded reliable diagnoses but also effectively treated PC. There was no need for additional antifungals after complete surgical resection.

Physiological and proteomic analysis of plant growth enhancement by the rhizobacteria Bacillus sp. JS.

In this study, the effects of the plant growth-promoting rhizobacterium (PGPR), Bacillus sp. JS on the growth of tobacco (Nicotiana tabacum 'Xanthi') and lettuce (Lactuca sativa 'Crispa'), were evaluated by comparing various growth parameters between plants treated with the bacterium and those exposed to water or nutrient broth as control. In both tobacco and lettuce, fresh weight and length of shoots were increased upon exposure to Bacillus sp. JS. To explain the overall de novo expression of plant proteins by bacterial volatiles, two-dimensional gel electrophoresis was performed on samples from PGPR-treated tobacco plants. Our results showed that chlorophyll a/b binding proteins were significantly up-regulated, and total chlorophyll content was also increased. Our findings indicate the potential benefits of using Bacillus sp. JS as a growth-promoting factor in agricultural practice, and highlight the need for further research to explore these benefits.

Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations for estimating glomerular filtration rates in cancer patients receiving cisplatin-based chemotherapy.

BACKGROUND: Although the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has been recommended for accurate estimates of glomerular filtration rate (eGFR), there is little information regarding differences in GFR estimates obtained using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations in East Asian cancer patients. We investigated discrepancies in GFR and toxicities in patients treated with cisplatin-based chemotherapy using three equations equations. METHODS: A total of 229 patients were retrospectively recruited. We calculated eGFR using the three equations and separated patients into three categories based on GFR < 10 (group A), 10-50 (group B), and > 50 (group C) mL/min/1.73m2. We analyzed chemotherapy toxicities. RESULTS: The mean eGFR calculated using the CG was the lowest of the values derived using the three equations. Estimates using the MDRD and CKD-EPI equations resulted in reclassifying 32 (71.1%) and 33 (73.3%) of 45 patients, originally placed in group B using the CG into group C. However, only 1 (7.7%) of 13 patients placed in group B using the MDRD were reclassified into group C using the CKD-EPI. Twenty-eight of 45 patients classified into group B using the CG equation were treated with reduced doses of cisplatin. However, these patients did not show significant differences in toxicities compared with other patients taking full doses of cisplatin. CONCLUSION: The CG equations underestimated GFR compared to the MDRD and CKD-EPI equations. Therefore, when GFR is estimated using CG equations, East Asian cancer patients may receive insufficient doses of chemotherapeutic agents, including cisplatin.

Activation of Pathogenesis-related Genes by the Rhizobacterium, Bacillus sp. JS, Which Induces Systemic Resistance in Tobacco Plants.

Plant growth promoting rhizobacteria (PGPR) are known to confer disease resistance to plants. Bacillus sp. JS demonstrated antifungal activities against five fungal pathogens in in vitro assays. To verify whether the volatiles of Bacillus sp. JS confer disease resistance, tobacco leaves pre-treated with the volatiles were damaged by the fungal pathogen, Rhizoctonia solani and oomycete Phytophthora nicotianae. Pre-treated tobacco leaves had smaller lesion than the control plant leaves. In pathogenesis-related (PR) gene expression analysis, volatiles of Bacillus sp. JS caused the up-regulation of PR-2 encoding ß-1,3-glucanase and acidic PR-3 encoding chitinase. Expression of acidic PR-4 encoding chitinase and acidic PR-9 encoding peroxidase increased gradually after exposure of the volatiles to Bacillus sp. JS. Basic PR-14 encoding lipid transfer protein was also increased. However, PR-1 genes, as markers of salicylic acid (SA) induced resistance, were not expressed. These results suggested that the volatiles of Bacillus sp. JS confer disease resistance against fungal and oomycete pathogens through PR genes expression.

Superior mesenteric vein thrombosis as an early presentation of myelodysplastic syndrome: a case report.

Mesenteric venous thrombosis (MVT) is a serious condition due to its potential association with mesenteric ischemia and infarction of the small bowel. Symptoms of MVT are often vague, making accurate diagnosis and sufficient treatment difficult. However, increased awareness and new imaging modalities for this condition have improved outcomes for patients with MVT. Treatment includes anticoagulation, transcatheter therapy, and surgery. In the present report, we describe the case study of a 62-year-old woman with a presenting diagnosis of superior MVT, who was finally diagnosed with myelodysplastic syndrome. The superior MVT spontaneously dissolved after the patient underwent 6 months of systemic anticoagulation therapy. Invasive surgery or bowel resection was not required.

CD26/DPP4 levels in peripheral blood and T cells in patients with type 2 diabetes mellitus.

CONTEXT: Dipeptidyl peptidase 4 (CD26/DPP4) is expressed on blood T cells and also circulates in a soluble form (sCD26/DPP4). OBJECTIVE: We aimed to evaluate blood T cell and circulating CD26/DPP4 and its association with metabolic parameters in patients with type 2 diabetes mellitus (T2DM). DESIGNS: We measured CD26/DPP4 expression (percentage of CD26(+) cells using flow cytometry) on CD4(+) and CD8(+) T cells, serum CD26/DPP4 level and activity, and various metabolic parameters in T2DM patients not on DPP4 inhibitor therapy (n = 148). Nondiabetic subjects (n = 50) were included as a control group. RESULTS: Compared with the healthy controls, CD26/DPP4 expression on CD4(+) T cells and CD8(+) T cells was higher in T2DM patients. Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group only when metformin and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or thiazolidinedione-treated T2DM patients had lower values compared with other T2DM patients. Various parameters in T2DM patients were related to CD26/DPP4 expression on the T cells (hemoglobin A1c), serum sCD26/DPP4 (hemoglobin A1c and insulin resistance assessed by updated homeostasis model assessment), and serum CD26/DPP4 activity (insulin resistance assessed by updated homeostasis model assessment, γ-glutamyl transferase, and alanine aminotransferase) by multivariate analyses. After active glucose control for 12 weeks in drug-naive T2DM patients (n = 50), CD26/DPP4 expression on blood T cells was significantly decreased. CONCLUSIONS: Our results suggest that the CD26/DPP4 level on blood T cells was associated with glucose control status in patients with T2DM.

Genome sequence of the plant growth-promoting rhizobacterium Bacillus sp. strain JS.

Volatile and nonvolatile compounds emitted from the plant growth-promoting rhizobacterium Bacillus sp. strain JS enhance the growth of tobacco and lettuce. Here, we report the high-quality genome sequence of this bacterium. Its 4.1-Mb genome reveals a number of genes whose products are possibly involved in promotion of plant growth or antibiosis.

Herbal cocktail ka-mi-kae-kyuk-tang stimulates mouse bone marrow stem cell hematopoiesis and janus-activated kinase 2/signal transducer and activator of transcription 5 pathway.

Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail. Our collaborative team has shown that it has potent anti-angiogenic, anti-cancer and anti-metastatic activities in vivo without observable side effects. We have documented evidence for KMKKT to alleviate drug-induced hematotoxicity in vivo. In the present study, we investigated the mechanistic and signaling events through which KMKKT enhances hematopoiesis, using hematopoietic stem cells (HSCs) isolated from the bone marrow of 8-12 week-old C57BL/6 mice. Our results show that KMKKT significantly increased the expression of the hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in HSCs. KMKKT also increased the expression of c-Kit, a cytokine receptor expressed in HSCs. In addition, KMKKT enhanced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5), and increased the binding activity of STAT5 to gamma interferon activated sites (GAS) that mediate JAK2 downstream signaling. Furthermore, we found that KMKKT significantly enhanced the growth rate of colony-forming unit granulocyte erythrocyte monocyte macrophages (CFU-GEMM) and burst forming unit erythroid (BFU-E) of mouse HSCs (mHSCs) stimulated by IL-3/EPO. Overall, our results demonstrated that KMKKT alleviated drug-induced side effects through enhanced hematopoiesis, at least in part through cytokine-mediated JAK2/STAT5 signaling.

Cadmium resistance in tobacco plants expressing the MuSI gene.

MuSI, a gene that corresponds to a domain that contains the rubber elongation factor (REF), is highly homologous to many stress-related proteins in plants. Since MuSI is up-regulated in the roots of plants treated with cadmium or copper, the involvement of MuSI in cadmium tolerance was investigated in this study. Escherichia coli cells overexpressing MuSI were more resistant to Cd than wild-type cells transfected with vector alone. MuSI transgenic plants were also more resistant to Cd. MuSI transgenic tobacco plants absorbed less Cd than wild-type plants. Cd translocation from roots to shoots was reduced in the transgenic plants, thereby avoiding Cd toxicity. The number of short trichomes in the leaves of wild-type tobacco plants was increased by Cd treatment, while this was unchanged in MuSI transgenic tobacco. These results suggest that MuSI transgenic tobacco plants have enhanced tolerance to Cd via reduced Cd uptake and/or increased Cd immobilization in the roots, resulting in less Cd translocation to the shoots.

JAK2/STAT5 signaling pathway mediates Bojungbangdocktang enhanced hematopoiesis.

Bojungbangdocktang (BJBDT) is a medicinal herbal cocktail that has been used for cancer prevention and treatment in traditional Korean medicine. In the current study, BJBDT was demonstrated to regulate hematopoiesis. BJBDT significantly increased the expression of hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in hematopoietic stem cells (HSCs). Additionally, BJBDT enhanced the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) and STAT binding to gamma interferon activated sites (GAS) in HSCs. Furthermore, BJBDT significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E) in vitro. Moreover, BJBDT increased the level of EPO at mRNA in kidney and plasma, and the numbers of erythroid-specific antigen Ter-119(+) erythroid cells in mice with aplastic anemia induced by 20% benzene. Consistently, histochemical staining revealed BJBDT increased the bone marrow and stromal cells as well as decreased macrophages and adipocytes in bone marrow tissues of mice with aplastic anemia. Taken together, the results suggest that BJBDT can enhance hematopoiesis via hematopoietic cytokine-mediated JAK2/STAT5 pathway as a potent hematopoietic candidate. Copyright © 2010 John Wiley & Sons, Ltd.

Alteration of floral organ identity by over-expression of IbMADS3-1 in tobacco.

The MADS-box genes have been studied mainly in flower development by researching flower homeotic mutants. Most of the MADS-box genes isolated from plants are expressed exclusively in floral tissues, and some of their transcripts have been found in various vegetative tissues. The genes in the STMADS subfamily are important in the development of whole plants including roots, stems, leaves, and the plant vascular system. IbMADS3-1, which is in the STMADS subfamily, and which has been cloned in Ipomoea batatas (L.) Lam., is expressed in all vegetative tissues of the plant, particularly in white fibrous roots. Sequence similarity, besides the spatial and temporal expression patterns, enabled the definition of a novel MADS-box subfamily comprising STMADS16 and the other MADS-box genes in STMADS subfamily expressed specifically in vegetative tissues. Expression of IbMADS3-1 was manifest by the appearance of chlorophyll-containing petals and production of characteristic changes in organ identity carpel structure alterations and sepaloidy of the petals. In reverse transcription-polymerase chain reaction analysis with a number of genes known to be key regulators of floral organ development, the flowering promoter NFL1 was clearly reduced at the RNA level compared with wild type in transgenic line backgrounds. Moreover, NtMADS5 showed slight down-regulation compared with wild-type plants in transgenic lines. These results suggest that IbMADS3-1 could be a repressor of NFL1 located upstream of NtMADS5. IbMADS3-1 ectopic expression is suggested as a possible means during vegetative development by which the IbMADS3-1 gene may interfere with the floral developmental pathway.

Hydrocinchonine, cinchonine, and quinidine potentiate paclitaxel-induced cytotoxicity and apoptosis via multidrug resistance reversal in MES-SA/DX5 uterine sarcoma cells.

Multidrug resistance (MDR) is one of important issues to cause the chemotherapy failure against cancers including gynecological malignancies. Despite some MDR reversal evidences of natural compounds including quinidine and cinchonine, there are no reports on MDR reversal activity of hydrocinchonine with its analogues quinidine and cinchonine especially in uterine sarcoma cells. Thus, in the current study, we comparatively investigated the potent efficacy of hydrocinchonine and its analogues quinidine and cinchonine as MDR-reversal agents for combined therapy with antitumor agent paclitaxel (TAX). Hydrocinchonine, cinchonine, and quinidine significantly increased the cytotoxicity of TAX in P-glycoprotein (gp)-positive MES-SA/DX5, but not in the P-gp-negative MES-SA cells at nontoxic concentrations by 3-(4,5-dimethylthiazol-2-yl)-2,5--diphenyltetrazolium bromide (MTT) assay. Rhodamine assay also revealed that hydrocinchonine, cinchonine, and quinidine effectively enhanced the accumulation of a P-gp substrate, rhodamine in TAX-treated MES-SA/DX5 cells compared with TAX-treated control. In addition, hydrocinchonine, cinchonine, and quinidine effectively cleaved poly (ADP-ribose) polymerase (PARP), activated caspase-3, and downregulated P-gp expression as well as increased sub-G1 apoptotic portion in TAX-treated MES-SA/DX5 cells. Taken together, hydrocinchonine exerted MDR reversal activity and synergistic apoptotic effect with TAX in MES-SA/DX5 cells almost comparable with quinidine and cinchonine as a potent MDR-reversal and combined therapy agent with TAX.