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Oncology Research 2024Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in...
BACKGROUND
Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.
METHODS
In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration.
RESULTS
After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% ( = 0.003) and 2% ( = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable.
CONCLUSIONS
In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
Topics: Animals; Taurine; Thiadiazines; Osteosarcoma; Mice; Disease Models, Animal; Bone Neoplasms; Tumor Burden; Microvascular Density; Mice, Inbred BALB C; Cell Line, Tumor; Antineoplastic Agents; Angiogenesis Inhibitors; Humans; Neovascularization, Pathologic
PubMed: 38948019
DOI: 10.32604/or.2024.050907 -
Biomedical Engineering Letters Jul 2024The sacroiliac joint (SIJ), a synovial joint with irregular surfaces, is crucial for stabilizing the body and facilitating daily activities. However, recent studies have...
PURPOSE
The sacroiliac joint (SIJ), a synovial joint with irregular surfaces, is crucial for stabilizing the body and facilitating daily activities. However, recent studies have reported that 15-30% of lower back pain can be attributed to instability in the SIJ, a condition collectively referred to as sacroiliac joint dysfunction (SIJD). The aim of this study is to investigate how the morphological characteristics of the auricular surface may influence the SIJ range of motion (ROM) and to examine differences in SIJ ROM between females and males, thereby contributing to the enhancement of SIJD diagnosis and treatment.
METHODS
We measured SIJ ROM using motion-analysis cameras in 24 fresh cadavers of Korean adults (13 males and 11 females). Using three-dimensional renderings of the measured auricular surface, we investigated the correlations between the morphological characteristics of the auricular surface and the ROM of the SIJ.
RESULTS
The SIJ ROM was between 0.2° and 6.7° and was significantly greater in females (3.58° ± 1.49) compared with males (1.38° ± 1.00). Dividing the participants into high-motion (3.87° ± 1.19) and low-motion (1.13° ± 0.62) groups based on the mean ROM (2.39°) showed no significant differences in any measurements. Additionally, bone defects around the SIJ were identified using computed tomography of the high-motion group. In the low-motion group, calcification between auricular surfaces and bone bridges was observed.
CONCLUSION
This suggests that the SIJ ROM is influenced more by the anatomical structures around the SIJ than by the morphological characteristics of the auricular surface.
PubMed: 38946817
DOI: 10.1007/s13534-024-00382-3 -
Cancer Biology & Therapy Dec 2024To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally...
To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (= -0.389, < .001) and GTV (= -0.211, < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group ( = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm group ( = .242) and GTV ≤ 68.8 cm group( = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.
Topics: Humans; Lymphopenia; Esophageal Squamous Cell Carcinoma; Male; Female; Middle Aged; Esophageal Neoplasms; Aged; Adult; Retrospective Studies; Prognosis; Aged, 80 and over; Tumor Burden; Lymphocyte Count; Radiotherapy Dosage
PubMed: 38946404
DOI: 10.1080/15384047.2024.2371632 -
Gynecological Endocrinology : the... Dec 2024To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles.
OBJECTIVE
To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles.
METHODS
This study was a retrospective cohort study. From October 2017 to April 2022, 412 fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group ( = 230):18.5 kg/m≤BMI < 24 kg/m; overweight group ( = 122): 24 kg/m≤BMI < 28 kg/m; Obesity group ( = 60): BMI ≥ 28 kg/m. Variables with < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol.
RESULTS
After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, < .05).
CONCLUSION
The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.
Topics: Humans; Female; Body Mass Index; Gonadotropin-Releasing Hormone; Progesterone; Adult; Retrospective Studies; Ovulation Induction; Hormone Antagonists; Fertilization in Vitro; Obesity; Overweight; Sperm Injections, Intracytoplasmic; Pregnancy
PubMed: 38946240
DOI: 10.1080/09513590.2024.2364892 -
Journal of Nutritional Science and... 2024This study examined the relationship between the frequency of consuming cold or hot meal/drink during summer and the nutritional status, appetite, and energy intake...
This study examined the relationship between the frequency of consuming cold or hot meal/drink during summer and the nutritional status, appetite, and energy intake among Japanese older people. The cross-sectional study was conducted in August 2021, targeting 60 adults aged 65 y and older. The Mini Nutritional Assessment (MNA) was used for nutritional status evaluation, the Simplified Nutritional Appetite Questionnaire (SNAQ) for appetite scoring, and food frequency questionnaire to assess energy intake. Participants reported on the frequency of consuming cold or hot meal/drink during the summer. Those who reported consuming hot meals "moderate" (p=0.033) or "frequent" (p=0.005) during summer had a higher BMI than those who reported minimal consumption. Participants who reported "frequent" consumption of hot meals in summer had higher MNA scores than those who reported "minimal" consumption (p=0.014). Participants who reported a "frequent" consumption of hot meals had higher SNAQ scores compared to those who reported "minimal" (p<0.001) or "moderate" (p=0.001). Similarly, participants who reported a "frequent" consumption of hot drinks had higher SNAQ scores than those reporting "minimal" (p=0.021) or "moderate" (p=0.008). The nutritional status and appetite during summer in Japanese older people were associated with the frequency of consuming hot meals and drinks.
Topics: Humans; Aged; Male; Nutritional Status; Female; Appetite; Japan; Cross-Sectional Studies; Energy Intake; Meals; Seasons; Aged, 80 and over; Nutrition Assessment; Hot Temperature; Surveys and Questionnaires; Body Mass Index; Feeding Behavior; Diet; East Asian People
PubMed: 38945895
DOI: 10.3177/jnsv.70.288 -
Journal of Nutritional Science and... 2024The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Milk Fat Globule Membrane Supplementation Following Exercise Training on Physical Performance in Healthy Young Adults: A Randomized Double-Blind, Placebo-Controlled Pilot Trial.
The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.
Topics: Humans; Double-Blind Method; Glycolipids; Lipid Droplets; Glycoproteins; Male; Young Adult; Female; Dietary Supplements; Muscle Strength; Body Composition; Exercise; Pilot Projects; Adult; Physical Functional Performance; Body Weight; Sphingomyelins; Muscle, Skeletal
PubMed: 38945893
DOI: 10.3177/jnsv.70.273 -
Journal of Nutritional Science and... 2024Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to...
Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to develop a formula to estimate the ideal body weight for each SMID patient, considering factors such as reduced muscle and bone mass. We analyzed data from 111 SMID patients (56 male, 55 female; age range 20 to 73 y) who underwent blood tests measuring creatinine (Cr) and cystatin C (cysC) for clinical reasons between Feb. 2018 and Feb. 2023. To create the optimal body weight formula, we utilized three variables: height, estimated glomerular filtration (eGFR)-Cr, and eGFR-cysC. The validity of the formula was assessed by comparing the measured triceps subcutaneous fat thickness (TSF) to the reference TSF (%TSF), evaluating how accurately it reflects the appropriate physique. The derived optimal body weight formula is as follows: Optimal body weight=(height)×(18.5-25.0)×{1-0.41×(1-eGFR-cysC/eGFR-Cr)}×0.93. Our formula demonstrated validity when using %TSF as an indicator. Establishing a method to determine optimal body weight in SMID patients, considering their low muscle and bone mass, is crucial for accurate nutritional assessment and subsequent nutritional management.
Topics: Humans; Female; Male; Middle Aged; Adult; Aged; Intellectual Disability; Creatinine; Young Adult; Body Weight; Cystatin C; Glomerular Filtration Rate; Nutrition Assessment; Ideal Body Weight; Body Height; Subcutaneous Fat; Motor Disorders
PubMed: 38945890
DOI: 10.3177/jnsv.70.248 -
Journal of Nutritional Science and... 2024Niacin is a cofactor in many biological reactions related to energy metabolism, redox reactions, DNA repair and longevity. Although it has been considered that...
Niacin is a cofactor in many biological reactions related to energy metabolism, redox reactions, DNA repair and longevity. Although it has been considered that increasing energy expenditure increases NAD consumption, little study has directly demonstrated the effect of exercise on niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic endurance exercise on niacin nutritional status, 4 wk old KMO mice were fed 4 or 30 mg/kg nicotinic acid containing diets, and forced to swim in a running water pool every other day for 35 d. The swim-exercised mice fed 4 mg/kg nicotinic acid diet showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the sedentary mice. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic endurance exercise failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic endurance exercise-induced growth retardation, their body weight rapidly increased. These results show that chronic endurance exercise impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic endurance exercise increases niacin requirement by increase of NAD consumption.
Topics: Animals; Niacin; Nutritional Status; Physical Conditioning, Animal; Male; Mice; Mice, Knockout; Physical Endurance; Liver; NAD; Swimming; Weight Gain; Diet; Body Weight; Mice, Inbred C57BL; Niacinamide
PubMed: 38945883
DOI: 10.3177/jnsv.70.185 -
The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321 -
The Lancet. Healthy Longevity Jul 2024Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated...
BACKGROUND
Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated with an increased risk of developing such hallmark-related diseases.
METHODS
In this multicohort study, we included people aged 38-72 years with data on weight, height, and waist circumference measured during a clinical examination at baseline between March 13, 2006, and Oct 1, 2010, from the UK Biobank with follow-up until Nov 12, 2021. To test reproducibility of the findings (replication analysis), we used data from people aged 40 years or older included in the Finnish Public Sector study and the Finnish Health and Social Support study who responded to the study surveys, had data on BMI, and were successfully linked to electronic health records from national registers up to Dec 31, 2016. Obesity and clinical characteristics were assessed at baseline. Via linkage to national health records, participants were followed up for 83 diseases related to nine ageing hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication). Outcomes were the first instance of hallmark-related disease, in addition to co-occurrence of three or more hallmark-related diseases and mortality.
FINDINGS
496 530 adults (mean age 57·0 years [SD 8·1]) from the UK Biobank were included in the primary analysis, and 83 249 (mean age 48·2 years [6·4]) adults from the Finnish cohorts were included in the replication analysis. Median follow-up was 12·7 years (IQR 12·0-13·4) in the UK Biobank and 14·0 years (8·0-15·0) in the Finnish cohorts. After adjusting for demographic characteristics, lifestyle factors, and depression, UK Biobank participants with obesity (BMI ≥30·0 kg/m) had a 1·40 (95% CI 1·38-1·41) times higher hazard ratio for the first hallmark-related disease than those with a healthy weight (BMI 18·5-24·9 kg/m). The corresponding hazard ratios for three co-occurring diseases were 2·92 (95% CI 2·64-3·22) for deregulated nutrient sensing, 2·73 (2·46-3·02) for telomere attrition, 2·33 (2·10-2·60) for epigenetic alterations, 2·30 (2·14-2·48) for mitochondrial dysfunction, 2·23 (2·04-2·45) for stem cell exhaustion, 2·02 (1·89-2·16) for altered intercellular communication, 2·01 (1·89-2·15) for cellular senescence, 1·83 (1·67-2·00) for loss of proteostasis, and 1·39 (1·27-1·52) for genomic instability. These findings were replicated in the Finnish cohorts. In both studies, the associations between other risk factors (low education, unhealthy dietary factors [available only in the UK Biobank], smoking, high alcohol consumption, physical inactivity, and depression) and hallmark-related diseases were weaker than those with obesity. 45-60% of the excess mortality in people with obesity was attributable to hallmark-related diseases.
INTERPRETATION
Obesity might have an important role in the development of diseases associated with cellular ageing. Tackling ageing mechanisms could potentially help to reduce the disease and mortality burden resulting from the obesity epidemic.
FUNDING
Wellcome Trust, UK Medical Research Council, US National Institute on Aging, Academy of Finland, and Finnish Foundation for Cardiovascular Research.
TRANSLATIONS
For the German and Finnish translations of the abstract see Supplementary Materials section.
Topics: Humans; Obesity; Middle Aged; Male; Female; Aged; Adult; Cellular Senescence; Finland; Cohort Studies; Risk Factors; Aging; United Kingdom; Body Mass Index
PubMed: 38945128
DOI: 10.1016/S2666-7568(24)00087-4