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The need for effective early diagnosis and management of NAFLD is urgent, considering the galloping incidence of the obesity and the fact that liver cirrhosis and HCC due to NAFLD will become the first indication for liver transplantation in foreseeable future.
The need for effective early diagnosis and management of NAFLD is urgent, considering the galloping incidence of the obesity and the fact that liver cirrhosis and HCC due to NAFLD will become the first indication for liver transplantation in foreseeable future.
Between 5 and 25% of patients with cutaneous lupus erythematosus (CLE) can progress to systemic lupus erythematosus (SLE) during the course of the disease. There is no clear predictive guideline for the progression of CLE to SLE.
Lupus erythematosus (LE), a chronic autoimmune disease, has a wide spectrum of manifestations. On one side of the spectrum is CLE, in which patients only display skin lesions. On the other side of the spectrum is SLE, which develops severe systemic involvement. CLE has even been considered as a separate entity from LE, while CLE is also proposed to be associated with SLE. In this review, the authors will describe the relationship between CLE and SLE; summarize the incidence, risk factors, systemic involvement, and management of patients who transition to SLE. The literature search was conducted mainly through PubMed from March to July 2020.
The identification of clinical characteristics and biomarkers in patients facing risk of developing SLE and monitoring the disease on a regular basis are essential to promptly manage and hopefully prevent transition to the systemic form.
The identification of clinical characteristics and biomarkers in patients facing risk of developing SLE and monitoring the disease on a regular basis are essential to promptly manage and hopefully prevent transition to the systemic form.Analysis of the literature data reveals that while inhibition of cancer-related carbonic anhydrase IX and XII isoforms continues to be an important enrichment factor for designing anticancer agent development libraries, exclusive reliance on the in vitro inhibition of these two recombinant isozymes in nominating candidate compounds for evaluation of their effects on cancer cells may lead not only to identifying numerous compounds devoid of the desired cellular efficacy but also to overlooking many promising candidates which may not display the best potency in biochemical inhibition assay. However, SLC-0111, now in phase Ib/II clinical trials, was developed based on the excellent agreement between the in vitro, in vivo and more recently, in-patient data.Chiliadenus montanus is a medicinal plant that grows in Sinai Peninsula in Egypt. Phytochemical investigation of C. montanus methanolic extract led to the isolation of five methoxy flavonoids; Chrysosplenol-D (1), 5,7,4'-trihydroxy- 3,3'-dimethoxy flavone (2), 5,7-dihydroxy -3,3',4'-trimethoxyflavone (3), Bonanzin (4), 3,5,6,7,4'-pentamethoxy flavone (5), a sesquiterpene, Cryptomeridiol (6) and stigmast-5,22-dien-3-O-β-D-glucopyranoside (7). The anti-inflammatory activity of compounds 2 and 5 was assessed in vitro on CaCo2 cells stimulated by lipopolysaccharide (LPS). Both compounds downregulated LPS-induced expression of inflammatory cytokines; tumor necrosis factor alpha (TNFα), interleukin 1β (IL1β), nuclear factor kappa B (NFκB), cyclooxygenase 1 (Cox1), cyclooxygenase 2 (Cox2), and 5-lipoxygenase (5Lox). In vivo, both compounds significantly decreased paw edema thickness in rats relative to carrageenan, showing better anti-inflammatory activity than celecoxib (36.98%) after 1 h (46.60% and 48.11%, respectively). selleck products An in silico study was performed, where both compounds were docked into the active site of the crystal structure of the human Cox2 enzyme.
Glioblastoma is a primary brain tumor with a poor prognosis despite multimodal therapy including surgery, radiotherapy and alkylating chemotherapy. Novel therapeutic options are therefore urgently needed; however, there have been various drug failures in late-stage clinical development. The proteasome represents a key target for anti-cancer therapy as successfully shown in multiple myeloma and other hematologic malignancies.
This review article summarizes the preclinical and clinical development of proteasome inhibitors in the context of glioblastoma.
Early clinical trials with bortezomib ended with disappointing results, possibly because this agent does not cross the blood-brain barrier. In contrast to bortezomib and other proteasome inhibitors, marizomib is a novel drug that displays strong inhibitory properties on all enzymatic subunits of the proteasome and, most importantly, crosses the blood-brain barrier, making it a potentially very active novel agent against intrinsic brain tumors. While preclinical studies have demonstrated significant anti-glioma activity, its clinical benefit has yet to be proven. Exploiting the biological effects of proteasome inhibitors in combination with other therapeutic strategies may represent a key next step in their clinical development.
Early clinical trials with bortezomib ended with disappointing results, possibly because this agent does not cross the blood-brain barrier. In contrast to bortezomib and other proteasome inhibitors, marizomib is a novel drug that displays strong inhibitory properties on all enzymatic subunits of the proteasome and, most importantly, crosses the blood-brain barrier, making it a potentially very active novel agent against intrinsic brain tumors. While preclinical studies have demonstrated significant anti-glioma activity, its clinical benefit has yet to be proven. Exploiting the biological effects of proteasome inhibitors in combination with other therapeutic strategies may represent a key next step in their clinical development.
Fatigue is one of the most consistent and distressing symptoms reported by adolescent/young adult (AYA) oncology patients. Bright white light (BWL) is used to treat fatigue in adult oncology but has not been explored in AYA oncology patients. The purpose of the current study was to determine the feasibility and acceptability of BWL for AYA who were receiving cancer-directed therapy.
51 AYA patients with newly diagnosed solid tumors, including lymphoma.
Participants were randomized to dim red light (DRL, n =25) or BWL (n=26) from devices retrofitted with adherence monitors for 30minutes upon awakening daily for 8weeks. Side effects were assessed via modified Systematic Assessment for Treatment-Emergent Effects (SAFTEE). Participants completed the PedsQL Multidimensional Fatigue Scale.
Of patients approached, 73% consented and participated. Mean adherence was 57% of days on study with 30.68 average daily minutes of usage. BWL did not cause more extreme treatment-emergent effects over DRL. Patients in the BWL group demonstrated significant improvement on all fatigue outcomes by both self-report and parent proxy report, which was not observed in the DRL group.
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