Summary
Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, ...and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel.
Introduction
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities.
Methods
The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line.
Results
A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels.
Conclusion
The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.
The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has ...been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population.
A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia.
A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7.
Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia.
Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated ...with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis.
Background Although ecologic association and animal studies support a direct effect of dietary fat on the development of breast cancer, results of epidemiologic studies have been inconclusive. ...Methods We prospectively analyzed the association between fat consumption and the incidence of postmenopausal invasive breast cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort comprising 188 736 postmenopausal women who completed a 124-item food-frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models with adjustment for energy and potential confounding factors. All statistical tests were two-sided. Results Over an average follow-up of 4.4 years, the cohort yielded 3501 cases of invasive breast cancer. The hazard ratio of breast cancer for the highest (median intake, 40.1% energy from total fat; 434 cases per 100 000 person-years) versus the lowest (median intake, 20.3% energy from total fat; 392 cases per 100 000 person-years) quintile of total fat intake was 1.11 (95% CI = 1.00 to 1.24; Ptrend = .017). The corresponding hazard ratio for a twofold increase in percent energy from total fat on the continuous scale was 1.15 (95% CI = 1.05 to 1.26). Positive associations were also found for subtypes of fat (hazard ratio for a twofold increase in percent energy from saturated fat = 1.13; 95% CI = 1.05 to 1.22; from monounsaturated fat, HR = 1.12; 95% CI = 1.03 to 1.21; from polyunsaturated fat, HR = 1.10, 95% CI = 1.01 to 1.20). Correction for measurement error in nutrient intakes, on the basis of a calibration substudy that used two 24-hour dietary recalls, strengthened the associations, yielding an estimated hazard ratio for total fat of 1.32 (95% CI = 1.11 to 1.58). Secondary analyses showed that associations between total, saturated, and monounsaturated fat intakes were confined to women who were not using menopausal hormone therapy at baseline. Conclusion In this large prospective cohort with a wide range of fat intake, dietary fat intake was directly associated with the risk of postmenopausal invasive breast cancer.
Summary
Background
Few large population‐based studies have compared the occurrence of peptic ulcer bleeding (PUB) in cirrhotic and noncirrhotic patients.
Aims
To investigate if cirrhotic patients ...have higher risk of PUB than the general population and to identify possible risk factors of PUB in cirrhotic patients.
Methods
Using the National Health Insurance Research Database, a nationwide population‐based dataset in Taiwan and matching age, gender, comorbidities and ulcerogenic medication by propensity score, 4013 cirrhotic patients, 8013 chronic hepatitis patients and 7793 normal controls were compared. The log‐rank test was used to analyse differences in accumulated PUB‐free survival rates between the groups. Cox proportional hazard regressions were performed to evaluate independent risk factors for PUB in all patients and identified risk factors of PUB in cirrhotic patients.
Results
During the 7‐year follow‐up, cirrhotic patients had significantly higher incidences of PUB than chronic hepatitis patients and controls, respectively (P < 0.001 by log‐rank test). By Cox proportional hazard regression analysis, cirrhosis was independently associated with increased risk of PUB (hazard ratio: 4.22; 95% CI 3.37–5.29, P < 0.001) after adjusting for age, gender, economic status, underlying comorbidities and ulcerogenic medication. Age, male, diabetes, chronic renal disease, history of gastro‐oesophageal variceal bleeding and use of nonsteroidal anti‐inflammatory drugs were risk factors for PUB in cirrhotic patients.
Conclusion
Cirrhotic patients have a significantly higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like age, gender, economic status, underlying comorbidities and ulcerogenic medication.
Abstract Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and ...invasion. Changes in O -glycans on β1-integrin have been found to regulate cancer cell behavior. We hypothesize that O -glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of β1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on β1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of β1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O -glycosylation for regulating EVT invasion.
Background
There is increasing use of anti‐osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse ...reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)‐SCAR.
Objective
To characterize patients with AOA‐SCAR and investigate the HLA association and utility of in vitro diagnostic methods.
Methods
We enrolled 16 cases with AOA‐cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens–Johnson syndrome SJS and 2 with drug rash with eosinophilia and systemic symptoms DRESS) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA‐SCAR, and tolerability to alternative drugs. We further performed literature review and meta‐analysis on the HLA association of AOA‐SCAR.
Results
Our data showed strontium ranelate is the most common causality of AOA‐SCAR in Asian populations. There was no cross‐hypersensitivity of SR‐SCAR with other AOA. HLA genotyping showed that SR‐SJS was most significantly associated with HLA‐A*33:03 (Pc = 5.17 × 10−3, OR: 25.97, 95% CI: 3.08–219.33). Meta‐analysis showed that HLA‐A*33:03 was associated with SR‐SJS (P = 5.01 × 10−5; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR‐SJS was 83.3%.
Conclusions
Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA‐A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR‐SCAR in patients whose reaction developed while taking multiple drugs.
Linked Commentary: T. Shiohara. J Eur Acad Dermatol Venereol 2021; 35: 567‐568. https://doi.org/10.1111/jdv.17138.
In total, 24 polycyclic aromatic hydrocarbons (PAHs) in both gas and particle phases and 35 nitro-PAHs in particle phase were analyzed in the exhaust from heavy-duty diesel vehicles equipped with ...after-treatment for particulate matter (PM) and NO
X
control. The test vehicles were carried out using a chassis dynamometer under highway cruise, transient Urban Dynamometer Driving Schedule (UDDS), and idle operation. The after-treatment efficiently abated more than 90% of the total PAHs. Indeed, the particle-bound PAHs were reduced by >99%, and the gaseous PAHs were removed at various extents depending on the type of after-treatment and the test cycles. The PAHs in gas phase dominated the total PAH (gas + particle phases) emissions for all the test vehicles and for all cycles; that is, 99% of the two-ring and 98% of the three-ring and 97% of the four-ring and 95% of the carcinogenic PAHs were in the gas-phase after a diesel particle filter (DPF) and not bound to the very small amount of particulate matter left after a DPF. Consequently, an evaluation of the toxicity of DPF exhaust must include this volatile fraction and cannot be based on the particle fraction only. The selective catalytic reduction (SCR) did not appear to promote nitration of the PAHs in general, although there might be some selective nitration of phenanthrene. Importantly the after-treatmtent reduced the equivalent BaP (BaPeq) emissions by >95%, suggesting a substantial health benefit.
Implications: This study demonstrated that after-treatments, including diesel particulate filters (DPF), diesel oxidation catalysts (DOC), and selective catalytic reduction (SCR), significantly reduce the emissions of PAHs from heavy-duty diesel engines. The gas-phase PAHs dominate the total PAH (gas + particle phases) emissions from heavy-duty diesel vehicles retrofitted with various DPFs and not bound to the very small amount of particulate matter left after a DPF. Consequently, an evaluation of the toxicity of DPF exhaust must also include this volatile fraction and cannot be based on the particle fraction only.
Supplemental Materials: Supplemental materials are available for this paper. Go to the publisher's online edition of the Journal of the Air & Waste Management Association.
Purpose
Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor ...necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD.
Methods
A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m
2
. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period.
Results
Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration HR 2.76, 95% confidence interval CI 1.36–5.60,
p
= 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03–3.69,
p
= 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86–10.65,
p
= 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria.
Conclusion
Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.
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