Erlandsenlausen7251

Polypeptides are useful in designing protein-polypeptide conjugates for therapeutic applications; however, they are not satisfactory in improving the stability of therapeutic proteins and extending their in vivo half-life. Here we show that thermally-induced self-assembly (TISA) of elastin-like polypeptide diblock copolymer fused interferon alpha (IFNα-ELPdiblock) into a spherical micelle can dramatically enhance the proteolytic stability of IFNα. Notably, the circulation half-life of IFNα-ELPdiblock micelle (54.7 h) is 124.3-, 5.7-, and 1.4-time longer than those of free IFNα (0.44 h), freely soluble IFNα-ELP (9.6 h), and PEGylated IFNα (39.0 h), respectively. Importantly, in a mouse model of ovarian tumor, IFNα-ELPdiblock micelle exhibited significantly enhanced tumor retention and antitumor efficacy over free IFNα, freely soluble IFNα-ELP, and even PEGylated IFNα. These findings provide a thermoresponsive supramolecular strategy of TISA to design protein-diblock copolypeptide conjugate micelles with enhanced stability and pharmacology.Excessive activation of NF-κB in macrophages contributes to the onset and exacerbation of inflammatory disorders. The NEMO binding domain (NBD) peptide is an NF-κB inhibitor peptide that binds to NEMO, one of components of the IκB kinase (IKK) complex, and inhibits the IKK kinase activity, in the cytosol. Because of this property, the NBD peptide is expected to inhibit NF-κB activation in macrophages. In this study, we developed a delivery carrier for NBD based on small extracellular vesicles (sEVs), which are membrane vesicles released from cells. We constructed fusion proteins comprising Gag (an sEV tropic protein) and one, three, or six repeats of NBD peptide (Gag-1NBD, Gag-3NBD, and Gag-6NBD, respectively) to load the NBD peptide to the inner space of the sEVs, and attempted the intracellular delivery of the NBD peptide to macrophages using Gag-NBD-loaded sEVs (nNBD-sEVs). learn more The nNBD-sEVs significantly inhibited LPS-induced phosphorylation of NF-κB pathway-related proteins in macrophages in a repeat number-dependent manner. Moreover, they exerted inhibitory effects on the NF-κB-dependent expression of proinflammatory mediators such as TNFα, CXCL10, iNOS, and NO. Collectively, our results indicate that NBD-containing sEVs can be used for the treatment of inflammatory diseases owing to their ability to effectively deliver peptides to the macrophage cytosol.

We used a quality improvement framework to transform two-day and in-person advanced communication training (ACT) course into a remote ACT (Re-ACT) format to help clinicians improve serious illness conversation (SIC) skills.

We assessed the reach, impact, and costs of Re-ACT and compared these measures to in-person ACT courses.

About 45-60minutes of synchronous, remote sessions consisting of a didactic introduction to SIC skills, tailored to the SARS-Cov-2 (COVID-19) crisis, and a live demonstration of SICs with patient-actors.

The transition to Re-ACT sessions resulted in reaching a greater number of clinicians in less time, although depth of content and opportunities for skill practice decreased. Although both formats were well received, Re-ACT respondents felt less prepared than ACT respondents to use SIC skills. The costs of Re-ACT were significantly less than in-person ACT courses.

We provided effective and well-received SIC training during a time of crisis. Future work should further define the optimal mix of in-person and remote experiences to teach SIC skills.

We provided effective and well-received SIC training during a time of crisis. Future work should further define the optimal mix of in-person and remote experiences to teach SIC skills.As a neuropsychiatric disorder, substance addiction represents a major public health issue with high prevalence and mortality in many countries. Recently, gut microbiota has been certified to play a part in substance addiction through various mechanisms. Hence, we mainly focused on three substance including alcohol, cocaine and methamphetamine in this review, and summarized their relationships with gut microbiota, respectively. Besides, we also concluded the possible treatments for substance addiction from the perspective of applying gut microbiota. This review aims to build a bridge between substance addiction and gut microbiota according to existing evidences, so as to excavate the possible bi-directional function of microbiota-gut-brain axis in substance addiction for developing therapeutic strategies in the future.Despite widespread evidence of endocannabinoid system involvement in the pathophysiology of psychiatric disorders, our understanding remains rudimentary. Here we review studies of the endocannabinoid system in humans with psychotic and mood disorders. Postmortem, peripheral, cerebrospinal fluid and in vivo imaging studies provide evidence for the involvement of the endocannabinoid system in psychotic and mood disorders. Psychotic disorders and major depressive disorder exhibit alterations of brain cannabinoid CB1 receptors and peripheral blood endocannabinoids. Further, these changes may be sensitive to treatment status, disease state, and symptom severity. Evidence from psychotic disorder extend to endocannabinoid metabolizing enzymes in the brain and periphery, whereas these lines of evidence remain poorly developed in mood disorders. A paucity of studies examining this system in bipolar disorder represents a notable gap in the literature. Despite a growing body of productive work in this field of research, there is a clear need for investigation beyond the CB1 receptor in order to more fully elucidate the role of the endocannabinoid system in psychotic and mood disorders.

Varioussystemic immunomodulating therapies have been used to treat toxic epidermal necrolysis (TEN), but their efficacy remains unclear.

To perform a systematic review and network meta-analysis (NMA) evaluating the effects of systemic immunomodulating therapies on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN.

A literature search was performed in online databases (from inception to October 31, 2019). Outcomes were mortality rates and Score of Toxic Epidermal Necrolysis (SCORTEN)-based standardized mortality ratio (SMR). A frequentist random-effects model was adopted.

Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments showed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (odds ratio, 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms showed that corticosteroids and intravenous immunoglobulin combination therapy was the only treatment with significant survival benefits (SMR, 0.