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1.
Public Health ; 230: 81-88, 2024 May.
Article in English | MEDLINE | ID: mdl-38518428

ABSTRACT

OBJECTIVES: Wildfire air pollution is a growing concern on human health. The study aims to assess the associations between wildfire air pollution and pregnancy outcomes in the Southwestern United States. STUDY DESIGN: This was a retrospective cohort study. METHODS: Birth records of 627,404 singleton deliveries in 2018 were obtained in eight states of the Southwestern United States and were linked to wildfire-sourced fine particulate matter (PM2.5) and their constituents (black carbon [BC] and organic carbon [OC]) during the entire gestational period. A double-robust logistic regression model was used to assess the associations of wildfire-sourced PM2.5 exposures and preterm birth and term low birth weight, adjusting for non-fire-sourced PM2.5 exposure and individual- and area-level confounder variables. RESULTS: Wildfire-sourced PM2.5 contributed on average 15% of the ambient total PM2.5 concentrations. For preterm birth, the strongest association was observed in the second trimester (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.05-1.07 for PM2.5; 1.06, 95% CI: 1.05-1.07 for BC; 1.04, 95% CI: 1.03-1.05 for OC, per interquartile range increment of exposure), with higher risks identified among non-smokers or those with low socio-economic status. For term low birth weight, the associations with wildfire-sourced PM2.5 exposures were consistently elevated for all trimesters except for the exposure averaged over the entire gestational period. Overall, the associations between wildfire-sourced PM2.5 and pregnancy outcomes were stronger than those with total PM2.5. CONCLUSIONS: Wildfire-sourced PM2.5 and its constituents are linked to higher risks of preterm birth and term low birth weight among a significant US population than the effects of ambient total PM2.5.


Subject(s)
Air Pollutants , Air Pollution , Premature Birth , Wildfires , Pregnancy , Female , Infant, Newborn , Humans , Premature Birth/epidemiology , Air Pollutants/analysis , Retrospective Studies , Maternal Exposure/adverse effects , Infant, Low Birth Weight , Particulate Matter/adverse effects , Particulate Matter/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Southwestern United States/epidemiology , Carbon , Birth Weight
2.
Sci Rep ; 13(1): 3674, 2023 03 04.
Article in English | MEDLINE | ID: mdl-36871083

ABSTRACT

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.


Subject(s)
Iron Overload , Thalassemia , Humans , Adult , Iron , Lung , Ferritins
4.
AJNR Am J Neuroradiol ; 44(1): 65-69, 2023 01.
Article in English | MEDLINE | ID: mdl-36521964

ABSTRACT

BACKGROUND AND PURPOSE: A cardiogenic embolus could reach the posterior circulation through the right vertebral artery because of a relatively larger diameter in cases of left vertebral artery hypoplasia. Hence, we investigated whether left vertebral artery hypoplasia is associated with cardiac embolisms with atrial fibrillation in the posterior circulation and its functional outcomes. MATERIALS AND METHODS: In this monocentric retrospective study, patients with acute cardioembolic stroke with atrial fibrillation were enrolled and underwent CT or neck MRA, which visualized the aortic arch and subclavian arteries. The laterality and size of vertebral artery hypoplasia were recorded. Posterior circulation stroke, basilar artery occlusion, and the functional outcomes after 3 months were investigated. RESULTS: This study included 407 patients; the patients with left vertebral artery hypoplasia experienced a higher rate of posterior circulation stroke (19 versus 73; 42.2% versus 20.2%; P = .001) and basilar artery occlusion (5 versus 10; 11.1% versus 2.8%; P = .005) than the patients without left vertebral artery hypoplasia. Multivariate analysis revealed that left vertebral artery hypoplasia showed an association with lower odds of achieving a good functional outcome 3 months after the stroke (OR = 0.4; 95% CI, 0.2-0.9; P = .027). CONCLUSIONS: Patients with cardioembolic stroke and left vertebral artery hypoplasia had posterior circulation stroke, basilar artery occlusion, and poor functional outcomes after 3 months.


Subject(s)
Arterial Occlusive Diseases , Atrial Fibrillation , Embolic Stroke , Stroke , Vertebrobasilar Insufficiency , Humans , Vertebral Artery/diagnostic imaging , Embolic Stroke/complications , Atrial Fibrillation/complications , Atrial Fibrillation/diagnostic imaging , Aorta, Thoracic , Retrospective Studies , Stroke/complications , Stroke/diagnostic imaging , Arterial Occlusive Diseases/complications , Vertebrobasilar Insufficiency/complications , Vertebrobasilar Insufficiency/diagnostic imaging
6.
Hong Kong Med J ; 28(3): 204-214, 2022 06.
Article in English | MEDLINE | ID: mdl-35697524

ABSTRACT

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.


Subject(s)
Neoplasm Recurrence, Local , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adolescent , Antineoplastic Combined Chemotherapy Protocols , Child , Child, Preschool , Disease-Free Survival , Humans , Incidence , Neoplasm Recurrence, Local/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Retrospective Studies , Survival Rate
7.
Pediatr Transplant ; 26(5): e14278, 2022 08.
Article in English | MEDLINE | ID: mdl-35396908

ABSTRACT

BACKGROUND: Hemoglobin (Hb) Hammersmith is a rare form of unstable ß-chain hemoglobinopathy causing hemolytic anemia. This rare event led to a more serious transfusion-dependent phenotype in a patient. It was successfully cured by haploidentical hematopoietic stem cell transplantation (HSCT). METHODS AND RESULTS: A 9-year-old mainland Chinese male with a history of neonatal unconjugated hyperbilirubinemia was diagnosed to have hemoglobin (Hb) Hammersmith. He required regular blood transfusion but was unable to be transfused to desired parameters for 8 years prior to transplant due to social and geographical reasons. He subsequently developed marrow hyperplasia and progressive splenomegaly (down to umbilicus level), suggestive of extramedullary hematopoiesis. Eventually, the family came to Hong Kong and complied to a more intensive transfusion regimen and preconditioning chemotherapy 3 months prior to transplant. He underwent haploidentical HSCT using paternal TCRαß/CD45RA-depleted graft but suffered from graft rejection, despite splenic irradiation for massive splenomegaly. It was successfully salvaged with second HSCT with unmanipulated graft from the same donor with additional serotherapy and donor lymphocyte infusions. CONCLUSION: Allogenic haploidentical HSCT for hemoglobin Hammersmith is feasible but adequate immunosuppression during conditioning is crucial. Precise adoptive cell therapy can promote durable engraftment.


Subject(s)
Hematopoietic Stem Cell Transplantation , Splenomegaly , Transfusion Reaction , Asian People , Child , Haploidy , Hemoglobins, Abnormal , Humans , Living Donors , Lymphocyte Transfusion , Lymphocytes , Male , Splenomegaly/etiology , Splenomegaly/therapy
8.
Ergonomics ; 65(12): 1639-1658, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35243968

ABSTRACT

Humans have developed a prolonged and special relationship with their tools, which themselves exhibit the propensity to become ever more intelligent across the years. A 'smart tool' is defined as to representing any entity, machine, or device that can complete an informational, mechanical, or electronic work. This work explains the development of the Smart Tool Proneness Questionnaire (STP-Q), which is designed to measure an individual's propensity to use smart tools. Data collection was designed to (1) identify the psychological dimensions underlying smart tool use (2) establish the questionnaire's reliability (3) validity, (4) propose a normalisation, and (5) provide an English translation of the French original. The work therefore implements a reliable and valid questionnaire, sensitive to inter-individual differences regarding the propensity to use smart tools. Statistical analysis reveals that the individual self-reported propensity for smart tool use rests on three factors (1) utilitarian use, (2) hedonic and social use, and (3) proneness to delegate. From a theoretical perspective, this individual propensity to use smart tools might be considered key to our species development. In practical terms, measuring an individual's propensity to use smart tools can be of considerable benefit to the design of future smart tools in both professional and non-professional settings. Practitioner summary: The STP-Q, a self-reported measure of an individual's propensity to use smart tools, was developed. STP-Q offers practitioners a measure of individual propensity to use smart tools along three dimensions: utilitarian use, hedonic and social use, and proneness to task delegate. Individual results can easily be interpreted from normalizations that STP-Q provides. Abbreviations: CFI: comparative fit index; GFI: goodness of fit index; IFI: incremental fit index; ISO: International Standardization Organization; IRB: institutional review board of the university of central Florida; IT: information technology; MATB: multi-attribute task battery; NMP-Q: no more phone phobia; RMSEA: root mean square error of approximation; STP-Q: smart tools proneness questionnaire; TAM: technology acceptance model; TRI: technology readiness index; UTAUT: unified theory of acceptance and use of technology; WAIS IV: Wechsler adult intelligence scale.


Subject(s)
Intelligence , Adult , Humans , Reproducibility of Results , Surveys and Questionnaires , Psychometrics
9.
Poult Sci ; 101(3): 101688, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35104730

ABSTRACT

Reduction of Salmonella on poultry carcasses is one way to prevent salmonellosis. The purpose of this research was to evaluate the effects of subzero saline chilling (SSC) with/without hot water spray (HWS) on broiler carcasses prior to chilling for bacterial reduction. Eviscerated broiler carcasses were subjected to water immersion chilling (WIC, 0% NaCl/0.5°C) or SSC (4% NaCl/-2.41°C) with/without prior HWS at 71°C for 1 min. Broiler carcasses in SSC were chilled faster than those in WIC, regardless of HWS. The combination of HWS and SSC resulted in the best reduction of mesophilic aerobic bacteria, Escherichia coli, and total coliforms on the carcasses over the WIC, SSC, and HWS/WIC. No Salmonella was detected on the carcasses in SSC and HWS/SSC while Salmonella positive was observed on the carcasses chilled in WIC and HWS/WIC. A trace of Gram-negative genus was detected on carcasses in HWS/SSC while many other microbiomes were observed on those in WIC, SSC, and HWS/WIC when quantitative microbiota profiles of 16S rRNA gene sequences were evaluated. Based on these results, chilling of broiler carcasses in 4% NaCl/-2.41°C after HWS at 71°C for 1 min significantly reduced carcass chilling time and bacterial contamination over the control chilling.


Subject(s)
Food Handling , Meat , Animals , Chickens/microbiology , Cold Temperature , Colony Count, Microbial/veterinary , Decontamination , Food Handling/methods , Food Microbiology , Meat/analysis , RNA, Ribosomal, 16S , Water
10.
Lett Appl Microbiol ; 74(2): 185-193, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34758116

ABSTRACT

Monochamus alternatus (Coleoptera: Cerambycidae; M. alternatus), popularly known as the Japanese pine sawyer, is a vector of pinewood nematode (Bursaphelenchus xylophilus) that causes pine wilt disease. A solid medium culture with M. alternatus produced Cordyceps militaris fruiting bodies with the longest strips and the highest biological efficiency. Supplementing the original form of M. alternatus with oats resulted in slightly enhanced fruiting body production. The original form of M. alternatus showed higher production than its powder form. The solid culture medium was optimized using a response surface methodology, and the optimal medium contained the following: 8·5 g per bottle of M. alternatus and 11·5 g per bottle of oats mixed with 22·4 ml of water in a 300-ml cylindrical plastic bottle. The optimal culturing period for the fruiting body formation was 37·1 days. Under these conditions, a fruiting body dry weight of 38·0 g per bottle (actual value) was attained. The fruiting body produced using a solid culture medium based on M. alternatus had a cordycepin content of about 25 µg g-1 . The solid culture medium containing M. alternatus is highly efficient and eco-friendly, and its effectiveness in large-scale fruiting body production from C. militaris has been demonstrated.


Subject(s)
Coleoptera , Cordyceps , Pinus , Animals
11.
Ultrasound Obstet Gynecol ; 59(6): 763-770, 2022 06.
Article in English | MEDLINE | ID: mdl-34931725

ABSTRACT

OBJECTIVES: To evaluate the short- and long-term outcome of late-preterm compared with term birth in twin pregnancy. METHODS: This retrospective observational cohort study included all women who had a twin delivery between 1 January 2007 and 31 December 2010 recorded in the claims database of the Korea National Health Insurance, with at least one follow-up recorded in the database of the National Health Screening Program for Infants and Children. Outcomes were analyzed at the pregnancy level, with adverse outcome being defined as an adverse outcome in one or both twins, identified by a diagnosis according to the International Classification of Diseases 10th Revision. The primary short-term outcome was composite morbidity, which included any of the following: transient tachypnea, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and bronchopulmonary dysplasia. Long-term adverse outcome included any neurological or neurodevelopmental outcome, defined by prespecified neurological and developmental diagnoses; these were assessed by following up all neonates until the end of 2018, by which time they were 8-11 years of age. Outcomes were compared between twins delivered late preterm (34 + 0 to 36 + 6 weeks) and those delivered at term (≥ 37 weeks). RESULTS: Among 17 189 women who delivered twins at ≥ 34 weeks of gestation during the study period, 5032 (29.27%) women delivered in the late-preterm period. On multivariate analysis, compared with the twins delivered at term, the late-preterm twins had an increased risk for the primary short-term outcome of composite morbidity (adjusted odds ratio (aOR), 2.09; 95% CI, 1.90-2.30), including transient tachypnea (aOR, 1.85; 95% CI, 1.64-2.09), respiratory distress syndrome (aOR, 2.31; 95% CI, 2.04-2.62), necrotizing enterocolitis (aOR, 2.10; 95% CI, 1.20-3.69) and intraventricular hemorrhage (aOR, 2.13; 95% CI, 1.46-3.11). For the long-term outcome, the late-preterm twins also had an increased risk for any neurological or neurodevelopmental outcome (adjusted hazard ratio, 1.14; 95% CI, 1.07-1.21). CONCLUSIONS: Twins delivered in the late-preterm period have an increased risk for short- and long-term morbidity compared with twins delivered at term. These results should be considered when determining the timing of delivery in uncomplicated twin pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Enterocolitis, Necrotizing , Infant, Newborn, Diseases , Premature Birth , Respiratory Distress Syndrome, Newborn , Child , Female , Hemorrhage , Humans , Infant , Infant, Newborn , Male , Pregnancy , Premature Birth/epidemiology , Respiratory Distress Syndrome, Newborn/epidemiology , Retrospective Studies , Tachypnea
12.
Pediatr Transplant ; 25(6): e14037, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34003560

ABSTRACT

BACKGROUND: Hemoglobin Bart's hydrops fetalis syndrome (BHFS) was once considered a fatal condition universally. Medical advances over the past three decades have resulted in increasing numbers of BHFS survivors. This retrospective review summarized local territory-wide experience and outcomes of BHFS patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in Hong Kong. METHODS: All BHFS patients who underwent allogeneic HSCT in Hong Kong, either in one of the two former pediatric transplant centers (Queen Mary Hospital and Prince of Wales Hospital) on or before 2019 or in the single territory-wide pediatric transplant center (Hong Kong Children's Hospital) since 2019, from January 1, 1996, till December 31, 2020, were included. Basic demographic data, perinatal history, transplant details, long-term outcomes, and morbidities were reviewed. RESULTS: Total five allogeneic HSCT were performed in two males and three females at a median age of 22 months, which include one 8/8 matched-sibling bone marrow transplant, one 5/6 matched-sibling cord blood transplant with HLA-DR antigenic mismatch, two 12/12 matched-unrelated peripheral blood stem cell transplant (PBSCT), and one haploidentical PBSCT with TCRαß/CD45RA depletion from maternal donor. Neutrophil and platelet engrafted (>20 × 109 /L) at a median of 15 and 22 days, respectively. All achieved near full donor chimerism at 1 month. All patients survived and remained transfusion-independent without significant morbidities with median follow-up duration of 10 years. CONCLUSION: To conclude, local data demonstrated favorable outcome of allogeneic HSCT for BHFS patients, but sample number is small. Non-directive approach in counseling and international collaboration is recommended.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hemoglobins, Abnormal , Hydrops Fetalis/therapy , Female , Hong Kong , Humans , Infant , Male , Retrospective Studies , Transplantation, Homologous
13.
Eur Rev Med Pharmacol Sci ; 25(6): 2463, 2021 03.
Article in English | MEDLINE | ID: mdl-33829427

ABSTRACT

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (3): 1198-1205-DOI: 10.26355/eurrev_202102_24822-PMID: 33629289, published online 15 February, 2021. After publication, the authors requested to correct Table I and some minor errors in the text. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/24822.

14.
Int J Oral Maxillofac Surg ; 50(9): 1233-1243, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33642154

ABSTRACT

A systematic review based on the PRISMA guidelines was conducted to investigate and compare treatment with hyaluronic acid (HA), corticosteroids, and blood products in patients with temporomandibular joint osteoarthritis (TMJOA). The MEDLINE/PubMed, Embase, and Cochrane Library databases were searched for articles published until September 25, 2019. Articles met the inclusion criteria if they reported patients with TMJOA, a comparison group, and a follow-up period of at least 6 months. The mean and standard deviation for TMJ pain and maximum mouth opening (MMO) were reported. Nine studies involving 443 patients were included. Injectables and Ringer's lactate solution or normal saline were reported to significantly improve TMJ pain and MMO. Regarding TMJ pain, two studies showed a significant superiority of plasma rich in growth factors (PRGF)/platelet-rich plasma (PRP) injections with or without arthrocentesis over HA, but HA showed a significant improvement compared to corticosteroids. For MMO, no injectable was found to be superior to Ringer's lactate or a normal saline control, but arthrocentesis + PRP resulted in MMO improvement compared to arthrocentesis + HA. Overall, all injectables in conjunction with arthrocentesis were efficient in alleviating pain and improving MMO in TMJOA patients; however, a meta-analysis was not possible due to heterogeneity across studies.


Subject(s)
Osteoarthritis , Platelet-Rich Plasma , Temporomandibular Joint Disorders , Humans , Hyaluronic Acid/therapeutic use , Injections, Intra-Articular , Osteoarthritis/drug therapy , Randomized Controlled Trials as Topic , Ringer's Lactate/therapeutic use , Temporomandibular Joint , Temporomandibular Joint Disorders/drug therapy , Treatment Outcome
15.
Eur Rev Med Pharmacol Sci ; 25(3): 1198-1205, 2021 02.
Article in English | MEDLINE | ID: mdl-33629289

ABSTRACT

Although obesity is known to have an influence on fracture, the relationship between lumbar and femur fractures and weight or waist circumference is controversial. We investigated the incidence of fracture with regards to waist circumference using the customised database of the Korean National Health Insurance Service (NHIS). Among 8,922,940 adults who participated at least twice in the NHIS National Health Check-up Program in South Korea between 2009 and 2011, 1,556,751 subjects (780,074 men and 776,677 women) were extracted. Over a mean follow-up of 6.5 years, multivariate-adjusted logistic regression analysis demonstrated that higher waist circumference was associated with an increased risk of femur fractures in both males and females. Moreover, the incidence of lumbar fractures was also positively associated with an increased waist circumference in males and females. An increased waist circumference showed a positive linear relationship with the risk of lumbar and femur fractures in both males and females.


Subject(s)
Femur/pathology , Spinal Fractures/pathology , Waist Circumference , Body Mass Index , Cohort Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Republic of Korea , Risk Factors
16.
Hum Exp Toxicol ; 40(2): 231-244, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32787465

ABSTRACT

Tomentosin, a sesquiterpene lactone, is known to possess various biological activities. However, its anticarcinogenic activity against human hepatocellular carcinoma (HCC) cells has not been investigated in detail. Thus, this study aimed to elucidate the cytotoxic mechanism of tomentosin in human HCC cell lines HepG2 and Huh7. WST-1, cell counting, and colony formation assay results showed that treatment with tomentosin decreased the viability and suppressed the proliferation rate of HepG2 and Huh7 cells in a dose- and time-dependent manner. Cell cycle analysis revealed increased population of cells at the SubG1 and G2/M stage, and decreased population of cells at the G0/1 stage in HepG2 and Huh7 cells treated with tomentosin. Annexin V/propidium iodide double staining and TUNEL assay results showed increased apoptotic cell population and DNA fragmentation in HepG2 and Huh7 cells treated with tomentosin. Western blotting analysis results showed that tomentosin treatment significantly increased the expression level of Bax, Bim (short form), cleaved PARP1, FOXO3, p53, pSer15p53, pSer20p53, pSer46p53, p21, and p27, but decreased the expression of Bcl2, caspase3, caspase7, caspase9, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclinB1, cyclinD1, cyclinD2, cyclinD3, and cyclinE in a dose-dependent manner. Taken together, this study revealed that tomentosin, which acted through cell cycle arrest and apoptosis, may be a useful therapeutic option against HCC.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Lactones/pharmacology , Liver Neoplasms/drug therapy , Sesquiterpenes/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/metabolism , Caspases/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , Forkhead Box Protein O3/metabolism , Humans , Liver Neoplasms/metabolism , Mitogen-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Tumor Suppressor Protein p53/metabolism
17.
Curr Oncol ; 27(4): e436-e439, 2020 08.
Article in English | MEDLINE | ID: mdl-32905211

ABSTRACT

Immunotherapy has emerged as a standard of cancer treatment, with an increasing number of indications. Recently, opportunistic infections have been reported in several cases in which immunotherapy has led to an increased susceptibility to infection. The present case is the first report of cytomegalovirus (cmv) gastritis occurring in a patient with melanoma during immunotherapy without immune-related adverse events (iraes) and without the use of immunosuppressant agents. A 43-year-old woman presented with stage iii malignant melanoma. She underwent wide excision of skin, with lymph node dissection, and she started immunotherapy with a 3-week cycle of pembrolizumab. The patient demonstrated stable disease response, and no iraes were observed during her initial treatment courses. However, after the 9th treatment cycle, she began to experience epigastric pain that worsened significantly, requiring a visit to the emergency centre. Imaging by computed tomography (ct) and integrated positron-emission tomography/ct revealed severe diffuse gastroduodenitis with acute pancreatitis. Esophagogastroduodenoscopy showed diffuse oozing, hemorrhagic, edematous, and exfoliative mucosa involving the entire gastric wall, defined as acute hemorrhagic gastritis. Biopsies of the gastric wall revealed cmv infection. Those findings were consistent with a diagnosis of cmv gastritis, and the patient received antiviral therapy with ganciclovir. After treatment, she recovered enough to resume immunotherapy. This case report presents a rare occurrence of cmv gastritis related to immunotherapy. As more patients are treated with immunotherapy, incidences of cmv infections are expected to increase; a high index of clinical suspicion is therefore needed in symptomatic patients.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Cytomegalovirus/growth & development , Gastritis/chemically induced , Melanoma/drug therapy , Adult , Female , Humans
18.
BMC Plant Biol ; 20(1): 167, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-32293285

ABSTRACT

BACKGROUND: Deoxyxylulose 5-phosphate synthase (DXS) and deoxyxylulose 5-phosphate reductoisomerase (DXR) are the enzymes that catalyze the first two enzyme steps of the methylerythritol 4-phosphate (MEP) pathway to supply the isoprene building-blocks of carotenoids. Plant DXR and DXS enzymes have been reported to function differently depending on the plant species. In this study, the differential roles of rice DXS and DXR genes in carotenoid metabolism were investigated. RESULTS: The accumulation of carotenoids in rice seeds co-expressing OsDXS2 and stPAC was largely enhanced by 3.4-fold relative to the stPAC seeds and 315.3-fold relative to non-transgenic (NT) seeds, while the overexpression of each OsDXS2 or OsDXR caused no positive effect on the accumulation of either carotenoids or chlorophylls in leaves and seeds, suggesting that OsDXS2 functions as a rate-limiting enzyme supplying IPP/DMAPPs to seed carotenoid metabolism, but OsDXR doesn't in either leaves or seeds. The expressions of OsDXS1, OsPSY1, OsPSY2, and OsBCH2 genes were upregulated regardless of the reductions of chlorophylls and carotenoids in leaves; however, there was no significant change in the expression of most carotenogenic genes, even though there was a 315.3-fold increase in the amount of carotenoid in rice seeds. These non-proportional expression patterns in leaves and seeds suggest that those metabolic changes of carotenoids were associated with overexpression of the OsDXS2, OsDXR and stPAC transgenes, and the capacities of the intermediate biosynthetic enzymes might be much more important for those metabolic alterations than the transcript levels of intermediate biosynthetic genes are. Taken together, we propose a 'Three Faucets and Cisterns Model' about the relationship among the rate-limiting enzymes OsDXSs, OsPSYs, and OsBCHs as a "Faucet", the biosynthetic capacity of intermediate metabolites as a "Cistern", and the carotenoid accumulations as the content of "Cistern". CONCLUSION: Our study suggests that OsDXS2 plays an important role as a rate-limiting enzyme supplying IPP/DMAPPs to the seed-carotenoid accumulation, and rice seed carotenoid metabolism could be largely enhanced without any significant transcriptional alteration of carotenogenic genes. Finally, the "Three Faucets and Cisterns model" presents the extenuating circumstance to elucidate rice seed carotenoid metabolism.


Subject(s)
Aldose-Ketose Isomerases/physiology , Carotenoids/metabolism , Erythritol/analogs & derivatives , Oryza/enzymology , Sugar Phosphates/physiology , Aldose-Ketose Isomerases/genetics , Butadienes/chemical synthesis , Butadienes/metabolism , Erythritol/genetics , Erythritol/physiology , Hemiterpenes/chemical synthesis , Hemiterpenes/metabolism , Plant Leaves/enzymology , Seeds/enzymology , Sugar Phosphates/genetics , Transferases/genetics , Transferases/physiology
19.
Sci Rep ; 10(1): 1254, 2020 01 27.
Article in English | MEDLINE | ID: mdl-31988376

ABSTRACT

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Radiotherapy/methods , Aged , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/radiotherapy , Male , Middle Aged , Palliative Care/methods , Radiotherapy Dosage , Severity of Illness Index , Survival Analysis , Treatment Outcome
20.
BMC Bioinformatics ; 20(1): 508, 2019 Oct 21.
Article in English | MEDLINE | ID: mdl-31638901

ABSTRACT

BACKGROUND: At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists. RESULTS: This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers. CONCLUSIONS: Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise.


Subject(s)
Computer Simulation , Models, Biological , Plants , Software , Internet , Systems Biology/methods , User-Computer Interface
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