Fyhnkjeldsen4950

The use of steroids to treat macular edema (ME) is a research hotspot in ophthalmology. We utilized CiteSpace and VOSviewer software to evaluate the Web of Science Core Collection publications and to build visualizing maps to describe the research progress in this topic. There were 3,252 publications for three decades during 1988-2021. The number of studies was low during the first 14 years but has risen consistently in the following two decades. The average publications per year were only 4.8 during 1988-2002, which jumped to 113 per year during 2003-2012, and 227 per year during 2013-2021. These publications came from 83 countries/regions, with the United States, Germany, and Italy leading positions. Most studies were published in Investigative Ophthalmology Visual Science, and Ophthalmology was the most cited journal. We found 9,993 authors, with Bandello F having the most publications and Jonas JB being the most frequently co-cited. According to our research, the most popular keyword is triamcinolone acetonide (TA). Macular edema, diabetic macular edema (DME), retinal vein occlusion (RVO), dexamethasone (DEX), fluocinolone acetonide (FA), and some other keywords were commonly studied in this field. In conclusion, the bibliometric analysis provides a comprehensive overview of steroid hotspots and developmental tendencies in the macular edema study. While anti-VEGF therapy is the first-line treatment for DME and RVO-induced macular edema, steroids implant is a valid option for these DME patients not responding to anti-VEGF therapy and non-DME patients with macular edema. Combined therapy with anti-VEGF and steroid agents is vital for future research.Oleandrin is a highly lipid-soluble cardiac glycoside isolated from the plant Nerium oleander (Apocynaceae) and is used as a traditional herbal medicine due to its excellent pharmacological properties. It is widely applied for various disease treatments, such as congestive heart failure. Recently, oleandrin has attracted widespread attention due to its extensive anti-cancer and novel anti-viral effects. However, oleandrin has a narrow therapeutic window and exhibits various toxicities, especially typical cardiotoxicity, which is often fatal. This severe toxicity and low polarity have significantly hindered its application in the clinic. This review describes natural sources, structural properties, and detection methods of oleandrin. Based on reported poisoning cases and sporadic animal experiments, the pharmacokinetic characteristics of oleandrin are summarized, so as to infer some possible phenomena, such as enterohepatic circulation. Moreover, the relevant factors affecting the pharmacokinetics of oleandrin are analyzed, and some research approaches that may ameliorate the pharmacokinetic behavior of oleandrin are proposed. With the toxicology of oleandrin being thoroughly reviewed, the development of safe clinical applications of oleandrin may be possible given potential research strategies to decrease toxicity.Background Metabolomics and onco-anesthesia are two emerging research fields in oncology. Metabolomics (metabolites analysis) is a new diagnostic and prognostic tool that can also be used for predicting the therapeutic or toxic responses to anticancer treatments. Onco-anesthesia studies assess the impact of anesthesia on disease-free and overall survival after cancer surgery. It has been shown that local anesthetics (LA), particularly lidocaine (LIDO), exert antitumor properties both in vitro and in vivo and may alter the biologic fingerprints of cancer cells. As LA are known to impair mitochondrial bioenergetics and byproducts, the aim of the present study was to assess the impact of LIDO on metabolomic profile of a breast cancer cell line. Methods Breast cancer MDA-MB-231 cells were exposed for 4 h to 0.5 mM LIDO or vehicle (n = 4). The metabolomic fingerprint was characterized by high resolution magic angle spinning NMR spectroscopy (HRMAS). The multivariate technique using the Algorithm to Determine Expecy. Future in vitro and preclinical studies are necessary to assess whether metabolomics analysis requires modification of local anesthetic techniques during tumor biopsy.Human arylamine N-acetyltransferase 1 (NAT1) catalyzes the N-acetylation of arylamine carcinogens such as 4-aminobiphenyl (ABP), and following N-hydroxylation, the O-acetylation of N-hydroxy-arylamine carcinogens such as N-hydroxy-ABP (N-OH-ABP). Genetic polymorphisms in NAT1 are linked to cancer susceptibility following exposures. The effects of individual single nucleotide polymorphisms (SNPs) in the NAT1 coding exon on Michaelis-Menten kinetic constants was assessed for ABP N-acetyltransferase and N-OH-ABP O-acetyltransferase activity following transfection of human NAT1 into COS-1 cells (SV40-transformed African green monkey kidney cells). NAT1 coding region SNPs 97C > T (rs56318881) (R33stop), 190C > T (rs56379106) (R64W), 559C > T (rs5030839) (R187stop) and 752A > T (rs56172717) (D251V) reduced ABP N- acetyltransferase and N-OH-ABP O-acetyltransferase activity below detection. 21T > G (rs4986992) (synonymous), 402T > C (rs146727732) (synonymous), 445G > A (rs4987076) (V149I), 613A > G (rs72554609) (M205V) and 640T > G (rs4986783) (S241A) did not significantly affect Vmax for ABP N-acetyltransferase or N-OH-ABP O-acetyltransferase. 781G > A (rs72554610) (E261K), and 787A > G (rs72554611) (I263V) slightly reduced ABP N-acetyltransferase and N-OH-ABP O-acetyltransferase activities whereas 560G > A (rs4986782) (R187Q) substantially and significantly reduced them. 560G > A (rs4986782) (R187Q) significantly reduced the apparent Km for ABP and N-OH-ABP a finding that was not observed with any of the other NAT1 SNPs tested. These findings suggest that the role of the 560G > A (rs4986782) (R187Q) SNP cancer risk assessment may be modified by exposure level to aromatic amine carcinogens such as ABP.Background Medication adherence is crucial for patients with mechanical heart valve replacement. Although families functioning is positively associated with medication adherence, little is known about the underlying mechanisms. Objective To test whether family functioning affects medication adherence through illness perceptions and whether this mediating effect was moderated by medication literacy. Methods 319 patients after mechanical heart valve replacement were included in this cross-sectional study from June 2021 to October 2021. Harringtonine mouse Data regarding family functioning, illness perceptions, medication adherence, and medication literacy were collected through questionnaires. The moderated mediation model was examined by Hayes's PROCESS macro, based on the bootstrapping method. Results The results revealed illness perceptions partially mediated the association of family functioning on medication adherence [β = 0.08, 95% confidence intervals (0.04, 0.12)], and this effect was stronger for patients with low medication literacy than those with high literacy [β = -0.36, 95% CI (-0.50, -0.22)]. Furthermore, the relationship between family functioning and medication adherence was only significant in patients with low medication literacy [β = 0.36, 95% CI (0.23, 0.50)]. Conclusion The mediating effect of illness perceptions between family functioning and medication adherence was moderated by medication literacy. Efforts to improve medication adherence by targeting at improving family functioning may be more effective when considering illness perceptions, especially for patients with limited medication literacy.Biowaiver based on the biopharmaceutics classification system (BCS) has been widely used in the global market for the approval of new generic drug products to avoid unnecessary in vivo bioequivalence (BE) studies. However, it is reported that three out of four formulations of dexketoprofen trometamol (DEX) tablets (BCS class I drug) failed the first BE study. The aim of this study was to determine whether the current biowaiver standard is reasonable for DEX. Thus, we successfully established a physiologically based pharmacokinetic (PBPK) model for DEX and examined the effects of dissolution, permeability, and gastric emptying time on DEX absorption under BCS-based biowaiver conditions using sensitivity analyses. Parameter sensitivity analysis showed that the dissolution rate in pH 1.2 media, permeability, and liquid gastric emptying time were sensitive parameters of Cmax. Therefore, gastric emptying variation was introduced into the PBPK model, and virtual BE studys were conducted on original research formulation and the formulation of the boundary dissolution rate (f2 = 50) prescribed by the biowaiver guideline. The virtual BE results showed dissolution rate changes within the biowaiver range will not cause high non-BE ratio, indicate waive of DEX generic drugs would not lead the risk of Cmax when generic products satisfy the requirements of biowaiver guideline. However, the effect of excipients on gastric emptying as a sensitive factor needs to be further studied when the rapid elimination of BCS class I drug is biowaived.Objective Intraplaque neovascularization is a marker of plaque vulnerability and is used to predict the risk of future vascular events in patients with symptomatic carotid stenosis; however, its association with asymptomatic carotid stenosis has not been prospectively evaluated. Therefore, this study aimed to explore the association between intraplaque neovascularization assessed using contrast-enhanced ultrasound and the occurrence of future ischemic events in asymptomatic patients diagnosed with carotid stenosis. Methods We recruited patients with asymptomatic carotid stenosis from our center. Contrast-enhanced ultrasound was performed at baseline. The outcomes were ischemic stroke and cardiovascular events. We plotted Kaplan-Meier survival curves and performed a log-rank test to compare endpoint event probability in patients with and without grade 2 intraplaque neovascularization. Univariate and multivariate Cox proportional hazards models were used to assess predictors of future vascular events. Results The data of 50 participants were included in the analysis (median follow-up, 43.7 months). Endpoint events occurred in 12 participants (24%). The Kaplan-Meier survival curves showed that patients with grade 2 intraplaque neovascularization had a higher probability of future vascular events than those with grades 0 and 1 (p less then .05). Grade 2 intraplaque neovascularization (hazard ratio 4.530, 95% confidence interval, 1.337-15.343, p less then .05) was an independent predictor of future vascular events in patients with asymptomatic carotid stenosis. Conclusion Grade 2 intraplaque neovascularization assessed using contrast-enhanced ultrasound independently predicted future ischemic events in patients with asymptomatic carotid stenosis, and contrast-enhanced ultrasound may be an effective screening method to identify high-risk subgroups of patients with asymptomatic carotid stenosis.Aims Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis.