Notes

Berberine from the Management of Neurodegenerative Diseases and Nanotechnology Made it possible for Specific Delivery.
Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC). Anlotinib hydrochloride is a novel multi-target tyrosine kinase inhibitor (TKI) exhibiting a superior overall response rate for brain metastases from NSCLC. The penetrability of anlotinib and three generations of epidermal growth factor receptor (EGFR) TKIs (osimertinib, afatinib and gefitinib) into brain microvascular endothelial cells (HBMECs) was compared.

A sensitive quantification method for the four TKIs was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Anlotinib and the three EGFR TKIs were separated on an ACQUITY BEH C18 column after a direct protein precipitation, and then analyzed using electrospray ionization in positive ion mode. The linearity, accuracy, precision, limit of quantification, specificity and stability were assessed.

The four analytes could be efficiently quantified in a single run of 3.8 min. The validation parameters of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The calibration range was 0.2-200 ng mL
for anlotinib and gefitinib, 1-500 ng mL
for osimertinib and 1-200 ng mL
for afatinib. The penetration of anlotinib across HBMECs was comparable with that of afatinib and gefitinib but less than that of osimertinib.

A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.
A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.Women of reproductive age (WRA) need adequate nutrient intakes to sustain a healthy pregnancy, support fetal growth, and breastfeed after childbirth. However, data on women's dietary intake in low- and middle-income countries (LMICs) are limited, and assessment of differences between dietary intakes of pregnant or lactating women compared with that of nonpregnant, nonlactating (NPNL) women is untested. Using single, multiple-pass 24-h dietary recall data from a sample of WRA residing in rural Bangladesh, we examined women's dietary intakes for energy, protein, calcium, iron, vitamin A, and dietary diversity for three groups NPNL (n = 2,903), pregnant (n = 197), and lactating women (n = 944). We used equivalence testing to examine similarity in adjusted intakes for pregnant versus NPNL women and lactating versus NPNL women with a predetermined equivalence threshold based on recommendations specific for each reproductive stage. On average, both pregnant and lactating women had insufficient intakes for all dietary measures. Although statistically significant differences were observed between pregnant and NPNL women for energy intake and dietary diversity and between lactating and NPNL women for energy and protein intake, the magnitudes of these differences were too small to reject equivalence. Statistical similarity was also evident in all micronutrients and dietary diversity for both two-group comparisons. Understanding statistical differences and similarities between dietary measures of women in distinct reproductive stages has important implications for the relevance, appropriateness, and evaluation of maternal diet-enhancing interventions in LMICs, especially during pregnancy and lactation, when demand for macronutrients and micronutrients is elevated.Eucommia leaf extract (ELE) is a traditional Chinese herbal medicine. We investigated the effect of ELE on the development of atherosclerosis and changes in peritoneal macrophage function in apolipoprotein E knockout (ApoE-/- ) mice. At 8 weeks of age, ApoE-/- mice were randomly divided into three groups that were fed a high-fat diet blended with 0% (control), 5% or 10% ELE for a period of 7 weeks. The 10% ELE dose caused an approximately 36% reduction in atherosclerotic lesions, as estimated by oil red O staining. Real-time PCR analysis showed that the 1-week treatment with ELE reduced mRNA levels of Tnf-alpha, Il-1, and Mif in peritoneal macrophages isolated from the ApoE-/- mice. Furthermore, a 1-week treatment with the 10% ELE diet significantly reduced migration and adhesion functions in peritoneal macrophages. These results suggest that a 10% ELE diet reduces atherosclerotic lesions and modulates macrophage function by reducing cytokine expression. PRACTICAL APPLICATION Eucommia leaf extract (ELE) is a traditional Chinese herbal medicine that reduces atherosclerotic lesions and suppresses inflammatory cytokines expression.
Mouse embryonic stem cell (mESC) culture contains various heterogeneous populations, which serve as excellent models to study gene regulation in early embryo development. The heterogeneity is typically defined by transcriptional activities, for example, the expression of Nanog or Rex1 mRNA. Our objectives were to identify mESC heterogeneity that are caused by mechanisms other than transcriptional control.

Klf3 mRNA and protein were analysed by RT-qPCR, Western blotting or immunofluorescence in mESCs, C2C12 cells, early mouse embryos and various mouse tissues. An ESC reporter line expressing KLF3-GFP fusion protein was made to study heterogeneity of KLF3 protein expression in ESCs. GFP-positive mESCs were sorted for further analysis including RT-qPCR and RNA-seq.

In the majority of mESCs, KLF3 protein is actively degraded due to its proline-rich sequence and highly disordered structure. Interestingly, KLF3 protein is stabilized in a small subset of mESCs. Transcriptome analysis indicates that KLF3-positive mESCs upregulate genes that are initially activated in 8-cell embryos. Consistently, KLF3 protein but not mRNA is dramatically increased in 8-cell embryos. Forced expression of KLF3 protein in mESCs promotes the expression of 8-cell-embryo activated genes.

Our study identifies previously unrecognized heterogeneity due to KLF3 protein expression in mESCs.
Our study identifies previously unrecognized heterogeneity due to KLF3 protein expression in mESCs.
To describe measurements of in vivo structures of the visual pathway beyond the retina and optic nerve head associated with canine primary angle-closure glaucoma (PACG).

A prospective pilot study was conducted using magnetic resonance diffusion tensor imaging (DTI) to obtain quantitative measures of the optic nerve, chiasm, tract, and lateral geniculate nucleus (LGN) in dogs with and without PACG. 3-Tesla DTI was performed on six affected dogs and five breed, age- and sex-matched controls. DTI indices of the optic nerve, optic chiasm, optic tracts, and LGN were compared between normal, unilateral PACG, and bilateral PACG groups. Intra-class correlation coefficient (ICC) was calculated to assess intra-observer reliability.

Quantitative measurements of the optic nerve, optic tract, optic chiasm, and LGN were obtained in all dogs. There was a trend for reduced fractional anisotropy (FA) associated with disease for all structures assessed. Compared to the same structure in normal dogs, FA, and radial diffusivity (RD) of the optic nerve was consistently higher in the unaffected eye in dogs with unilateral PACG. Intra-observer reliability was excellent for measurements of the optic nerve (ICC 0.92), good for measurements of the optic tract (ICC 0.89) and acceptable for measures of the optic chiasm (ICC 0.71) and lateral geniculate nuclei (ICC 0.76).

Diffusivity and anisotropy measures provide a quantifiable means to evaluate the visual pathway in dogs. DTI has potential to provide in vivo measures of axonal and myelin injury and transsynaptic degeneration in canine PACG.
Diffusivity and anisotropy measures provide a quantifiable means to evaluate the visual pathway in dogs. DTI has potential to provide in vivo measures of axonal and myelin injury and transsynaptic degeneration in canine PACG.
Of all newborns, 1%-2% are born very preterm (VP; <32weeks) or with very low birthweight (VLBW; ≤1500g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow-up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; lated biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction.
The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction.
The evidence for manualized psycho-educative family intervention (FI) in first-episode psychosis (FEP) is well-established to reduce relapse and caregiver distress. Less is known, however, about type and duration of FI.

To compare two different types of manualized family interventions for FEP Multi-Family Groups (MFG) and Single-Family Intervention (SFI).

This was a prospective, quasi-experimental cohort study of all participants of an early psychosis service (OPUS) with an ICD-10 diagnosis of F20 to F29 (excl. F21), aged 18 to 35 years, in Psychiatry Region Zealand, Denmark, during a 2-year period. All service users and their relatives are offered FI, either MFG or SFI. Assessment of level of participation, psychopathology measured by The Positive and Negative Syndrome Scale (PANSS), remission status and relapses was carried out at 3-year follow up.

We found no differences between the service users participating in SFI (N = 25) or MFG (N = 18) on number of readmissions or relapses after baseline or psychopathology. A binary logistic regression analysis on remission status at follow up showed a trend in favour of MFG. A surprisingly high proportion of the families did not receive an FI.

SFI and MFG seem equally effective in an FEP programme. The low attendance of FI may be due to several issues-among others, the probability that the FI did not sufficiently match the needs of the service users. Further studies involving larger samples are needed, included randomized controlled trials and implementation studies.
SFI and MFG seem equally effective in an FEP programme. this website The low attendance of FI may be due to several issues-among others, the probability that the FI did not sufficiently match the needs of the service users. Further studies involving larger samples are needed, included randomized controlled trials and implementation studies.
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