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Persistent psychotic symptomatology might be present in a group of patients with borderline personality disorder (BPD) according to recent research findings.
Investigate whether psychotic symptoms could be associated to greater cognitive and functional impairment in BPD patients.
In this observational, cross-sectional study (PI14/01449 and PI17/01023), we investigated the incidence of persistent psychotic symptoms in BPD patients and its association with specific neurocognitive impairments. A sample of 120 patients with diagnosis of BPD according to DSM IV TR was studied.
A substantial number of BPD patients (52, 43,3%) presented psychotic symptoms for a period longer than 6 months. Among BPD patients with psychotic symptoms, 25 (48%) presented hallucinations, 35 (67,3%) presented delusional thoughts and 8 patients (15%) presented both. BPD psychotic patients had greater global severity at the CGI than non-psychotic patients (p 0.02). Psychotic BPD patients had greater impairment in attention (Hedges o design adjusted treatment interventions.An approach of building block (BB) inclusivity and atom efficient library schemes deliver the quality and diversity of DNA-encoded libraries best suited for small molecule drug discovery. In this Perspective, we offer key learnings in DEL design from a decade's worth of DEL-driven screening.The RSK2 kinase is the downstream effector of the Ras/Raf/MEK/ERK pathway, that is often aberrantly activated in acute myeloid leukemia (AML). Recently, we reported a structure-activity study for BI-D1870, the pan-RSK inhibitor, and identified pteridinones that inhibited cellular RSK2 activity that did not result in concomitant cytotoxicity. In the current study, we developed a series of pyrrolopyrimidines and purines to replace the pteridinone ring of BI-D1870, with a range of N-substituents that extend to the substrate binding site to probe complementary interactions, while retaining the 2,6-difluorophenol-4-amino group to maintain interactions with the hinge domain and the DFG motif. Several compounds inhibited cellular RSK2 activity, and we identified compounds that uncoupled cellular RSK2 inhibition from potent cytotoxicity in the MOLM-13 AML cell line. These N-substituted probes have revealed an opportunity to further examine substituents that extend from the ATP- to the substrate-binding site may confer improved RSK potency and selectivity.Chemical knockdown of therapeutic targets using proteolysis targeting chimeras (PROTACs) is a rapidly developing field in drug discovery, but PROTACs are bifunctional molecules that generally show poor bioavailability due to their relatively high molecular weight. click here Recent developments aimed at the development of next-generation PROTACs include the in vivo synthesis of PROTAC molecules, and the exploitation of PROTACs as chemical tools for in vivo synthesis of ubiquitinated proteins. This short review covers recent advances in these areas and discusses the prospects for in vivo synthetic PROTAC technology.Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs' psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.Accumulating evidence indicates that a dysregulated kynurenine (KYN) pathway (KP) metabolism may play an important role in the pathogenesis of both schizophrenia and metabolic syndrome (MS). However, the underlying mechanisms remain poorly understood. Here, we aimed to evaluate the potential roles of KP in the pathogenesis of MS in schizophrenia. A total of 160 schizophrenia patients and 70 healthy controls were enrolled in this study. KP metabolites were quantified, and MS scores were calculated, for comparisons between patients and controls. Associations among the indices were explored in both groups. Multiple linear regression analyses were performed to investigate the effects of KP metabolites on MS factors. We observed a significantly higher MS score, lower levels of all KP metabolites, and higher nicotinamide adenine dinucleotide (NAD+)/quinolinic acid (QUNA) in patients than in controls (all p less then 0.01). Partial correlation analyses revealed that, in the patient group, QUNA and QUNA/KYN correlated positively with MS score (r = 0.24 and 0.27, respectively, both p less then 0.025), and NAD+/QUNA correlated negatively with MS score (r = -0.25, p = 0.002). Results of multiple regression analyses showed significant QUNA × group interactions in the model representing QUNA effects on MS score (β = 0.25) and a significant QUNA/KYN × group interaction in the model representing QUNA/KYN effects on MS score (β = 0.23) (both p less then 0.001). Among all factors contributing to MS in schizophrenia, an interactive effect of schizophrenia itself and dysregulated KP plays a contributory role. Conceivably, modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously.
Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease that leads to scar formation. The immune pathogenesis of HS is not fully understood and inhibitors of tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-1, IL-23 can be used for treating HS. Identification of serum biomarkers may help understanding individual differences in HS pathogenesis, evaluating disease severity and developing more effective treatment methods.
To assess the serum levels of proinflammatory cytokines TNF-α, IL-1β, IL-17A, IL-23 and high-sensitivity C-reactive protein (hs-CRP) in patients with HS and to evaluate the impact of treatment on cytokine levels.
Serum proinflammatory cytokine and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits in 24 healthy controls and in 26 HS patients at baseline and after a 3-month treatment. Patients were treated with clindamycin, adalimumab, dapsone, doxycycline and acitretin, based on HS condition and laboratory results. Control, pre-treatment and post-treatment values were compared.