Notes

Iron homeostasis inside arthropathies: Coming from pathogenesis to be able to healing potential.
Response to the coronavirus disease 2019 (COVID-19) pandemic has resulted in shelter-in-place orders and major changes to individuals' daily lives. The impact of such stressors on disease activity in individuals with axial spondyloarthritis (axSpA) is unclear. The aim of this study is to examine whether stress, anxiety, and depression are associated with patient-reported disease activity, after accounting for important factors.

We administered a survey to an axSpA cohort from a single center with well-defined demographic and disease characteristics. We included questions about job status changes, exercise, medication use, disease activity (by the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and psychological factors (stress, depressive symptoms, and anxiety). Separate multivariable linear models examined the associations between perceived stress, anxiety, and depression with the BASDAI.

After adjustment for potential confounders, those with higher levels of stress had a statistically significant 0.54-point higher BASDAI, on average, compared with those with lower levels of stress (95% confidence interval [CI] 0.11, 0.97). Those with higher levels of anxiety also had a statistically significant higher BASDAI, on average, compared with those with lower levels of anxiety (β 0.95, 95% CI 0.18, 0.99). The association between depression and BASDAI was not statistically significant. We did not find differences in these associations among subgroups of age, job status, or county of residence.

Individuals with axSpA with higher levels of stress and anxiety had significantly higher disease activity levels, although with a difference below clinical importance. Further planned studies will evaluate the trajectory of disease activity.
Individuals with axSpA with higher levels of stress and anxiety had significantly higher disease activity levels, although with a difference below clinical importance. Further planned studies will evaluate the trajectory of disease activity.Anticancer drug-loaded nanoparticles have been explored extensively to decrease side effects while improving their therapeutic efficacy. However, due to the low drug loading content, premature drug release, nonstandardized carrier structure, and difficulty in predicting the fate of the carrier, only a few nanomedicines have been approved for clincial use. Herein, a carrier-free nanoparticle based on the self-assembly of the curcumin-erlotinib conjugate (EPC) is developed. The EPC nanoassembly exhibits more potent cell killing, better antimigration, and anti-invasion effects for BxPC-3 pancreatic cancer cells than the combination of free curcumin and erlotinib. Furthermore, benefiting from both passive and active tumor targeting effect, EPC nanoassembly can effectively accumulate in the tumor tissue in a xenograft pancreatic tumor mouse model. Consequently, EPC effectively reduces the growth of pancreatic tumors and extends the median survival time of the tumor-bearing mice from 22 to 68 days. In addition, no systemic toxicity is detected in the mice receiving EPC treatment. Attributed to the uniformity of the curcumin-erlotinib conjugate and easiness of scaling up, it is expected that the EPC can be translated into a powerful tool in fighting against pancreatic cancer and other epidermal growth factor receptor positive cancers.Chemotherapy, combined with other treatments, is widely applied in the clinical treatment of cancer. However, deficiencies inherited from the traditional route of administration limit its successful application. With the development of nanotechnology, a series of smart nanodelivery systems have been developed to utilize the unique tumor environment (pH changes, different enzymes, and redox potential gradients) and exogenous stimuli (thermal changes, magnetic fields, and light) to improve the curative effect of anticancer drugs. In this review, endogenous and exogenous stimuli are briefly introduced. Epigenetics inhibitor Among these stimuli, various redox-sensitive linkages are primarily described in detail, and their application with self-assembled nanoparticles is recounted. Finally, the application of redox-responsive self-assembled nanoparticles in cancer therapy is summarized.
Diuretic resistance is a common complication impairing decongestion during hospitalization for acute decompensated heart failure (ADHF). The current understanding of diuretic resistance mechanisms in ADHF is based upon extrapolations from other disease states and healthy volunteers. However, accumulating evidence suggests that the dominant mechanisms in other populations have limited influence on diuretic response in ADHF. Additionally, the ability to rapidly and reliably diagnose diuretic resistance is inadequate using currently available tools.

The Mechanisms of Diuretic Resistance (MDR) Study is designed to rigorously investigate the mechanisms of diuretic resistance and develop tools to rapidly predict diuretic response in a prospective cohort hospitalized with ADHF.

Study assessments occur serially during the ADHF hospitalization and after discharge. Each assessment includes a supervised 6-hour urine collection with baseline blood and timed spot urine collections following loop diuretic administration. Patient characteristics, medications, physical exam findings, and both in-hospital and post-discharge HF outcomes are collected. Patients with diuretic resistance are eligible for a randomized sub-study comparing an increased loop diuretic dose with combination diuretic therapy of loop diuretic plus chlorothiazide.

The Mechanisms of Diuretic Resistance Study will establish a prospective patient cohort and biorepository to investigate the mechanisms of diuretic resistance and urine biomarkers to rapidly predict loop diuretic resistance.
The Mechanisms of Diuretic Resistance Study will establish a prospective patient cohort and biorepository to investigate the mechanisms of diuretic resistance and urine biomarkers to rapidly predict loop diuretic resistance.A Meiothermus strain capable of using β-phenylalanine for growth is isolated by culture enrichment of samples collected in hot environments and the genome is sequenced showing the presence of 22 putative transaminase (TA) sequences. On the basis of phylogenetic and sequence analysis, a TA termed Ms-TA2 is selected for further studies. The enzyme is successfully produced in Escherichia coli Rosetta(DE3) cells, with 70 mg of pure protein obtained from 1 L culture after purification by affinity chromatography. Ms-TA2 shows high activity toward (S)-β-phenylalanine and other (S)-β-amino acids, as well as a preference for α-ketoglutarate and aromatic aldehydes as amino acceptors. Moreover, Ms-TA2 is shown to be a thermostable enzyme by maintaining about 60% of the starting activity after 3 h incubation at 50 °C and showing a melting temperature of about 73 °C. Finally, a homology-based structural model of Ms-TA2 is built and key active site interactions for substrate and cofactor binding are analyzed.
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