Immunomodulatory and anti-angiogenesis effects of excavatolide B and its derivatives in alleviating atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 µM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1ß, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.

Patient Unpunctuality's Effect on Appointment Scheduling: A Scenario-Based Analysis.

This study examined patient unpunctuality's effect on patient appointment scheduling in the ultrasound department of a hospital. The study created a simulation system incorporating the formulated F3 distribution to describe patient unpunctuality. After the simulation model passed verification and validation processes, what-if scenarios were conducted under two policies: The preempt policy and the wait policy. A comparison of the total cost of each policy showed that the preempt policy performed better than the wait policy in the presence of unpunctuality. The study used sensitivity analyses to identify the different effects of patient unpunctuality on the system. The weights of the cost coefficient of both radiological technician's idle time and patient waiting time must be equal in order to achieve a lower cost. The patient's inter-arrival time must be close to the average total time in the system to achieve lower costs. Moreover, utilization decreases as the patient's inter-arrival increases. Therefore, the patient's inter-arrival time should be higher than, but close to, the service time to ensure less radiological technician's idle time and patient waiting time.

Serum ApoA4 levels predicted the progression of renal impairment in T2DM.

BACKGROUND: Among multiple causes, diabetic nephropathy (DN) is the major underlying renal disease that leads to end-stage renal disease (ESRD), and early diagnosis can effectively prevent or delay the progression to ESRD. Therefore, the current study aimed to develop noninvasive, accurate detection markers. MATERIALS & METHODS: For this study, 62 diabetes mellitus (DM) patients, 59 DN patients and 21 healthy controls (HCs) were recruited. All participants' serum samples were subjected to concavanalin (Con) A affinity chromatography, which utilizes glycoproteins to discover potential markers. RESULTS: From nano LC-MS and Western blot analysis, apolipoprotein A-IV (ApoA4) was selected which featured a gradual, almost twofold increase in the order of HC, DM and DN. In the Con A-based ELISA, the DM group was 1.91-fold higher than the HC group, while the DN group was 2.56-fold higher than the HCs and 1.33-fold higher than the DM group. In addition, significant positive correlations were observed between ApoA4 and blood urea nitrogen levels and between ApoA4 and creatine levels, while significant negative correlations were seen between serum protein levels and between serum albumin levels in comparisons of DM and DN samples. CONCLUSIONS: Serum Con A-bound ApoA4 levels were higher in the DM group than in HCs, and further increased in the DN group. Levels of ApoA4 were positively correlated with blood urea nitrogen and creatine, but negatively correlated with serum protein and albumin. This evidence supports serum Con A-bound ApoA4 as a circulating marker for predicting the progression of renal impairment in DM patients.

Data-driven desirability function to measure patients' disease progression in a longitudinal study.

Multiple outcomes are increasingly used to assess chronic disease progression. We discuss and show how desirability functions can be used to assess a patient overall response to a treatment using multiple outcome measures and each of them may contribute unequally to the final assessment. Because judgments on disease progression and the relative contribution of each outcome can be subjective, we propose a data-driven approach to minimize the biases by using desirability functions with estimated shapes and weights based on a given gold standard. Our method provides each patient with a meaningful overall progression score that facilitates comparison and clinical interpretation. We also extend the methodology in a novel way to monitor patients' disease progression when there are multiple time points and illustrate our method using a longitudinal data set from a randomized two-arm clinical trial for scleroderma patients.

Anti-melanogenic effects of δ-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells.

Tocotrienols are known to possess potent antioxidant, anticancer, and cholesterol lowering activities. Being able to rapidly penetrate the skin, these vitamin E isoforms have been explored for potential treatment against melanoma. This study aimed to elucidate the mechanism involved in the anti-melanogenic effects of δ-tocotrienol (δT3) in B16 melanoma cells. Results showed that at 20 µM of δT3 significantly inhibited melanin formation and ROS generation. Treatment with δT3 also effectively suppressed the expression of melanogenesis-related proteins, including MC1R, MITF, TYRP-1, and TYRP-2. More importantly, we observed that the mitogen-activated protein kinase (MAPK) pathway was involved in mediating δT3's inhibitory effect against melanin production. Specifically, δT3 treatment markedly induced the activation of extracellular signal-regulated kinases (ERK). The use of ERK activation inhibitor (PD98059) abrogated the δT3-mediated downregulation expression melanogenesis-related proteins and restored melanin production. Furthermore, siRNA targeting ERK effectively blocked the δT3-induced repression of tyrosinase and TYRP-1 expression. These results suggest that δT3's inhibitory effect against melanogenesis is mediated by the activation of ERK signaling, thereby resulting in downstream repression of melanogenesis-related proteins and the subsequent melanin production. These data provide insight to δT3's effect and the targeting of ERK signaling for treatment against melanogenesis.

Effects of thermal therapy on uremic pruritus and biochemical parameters in patients having haemodialysis.

TITLE: Effects of thermal therapy on uremic pruritus and biochemical parameters in patients having haemodialysis. AIM: This paper is a report of a trial to identify the effect of thermal therapy with far-infrared rays in comparison with non-thermal therapy on uremic pruritus and biochemical parameters. BACKGROUND: Uremic pruritus remains one of the most frustrating, common, and potentially disabling symptoms in patients undergoing haemodialysis. The mechanism underlying uremic pruritus is poorly understood. Although enough is known to determine a reasonable treatment approach, more research is needed to evaluate more reliable treatments. METHODS: A randomized, double-blind, controlled trial was conducted in 2005 using questionnaires and measurement of blood biochemical parameters. A total of 41 uremic patients on maintenance haemodialysis were randomly assigned either to the thermal therapy group or the control group. The thermal therapy group was treated with 40 degrees C thermal therapy with far-infrared rays at the Sanyinjiao acupoint for 15 minutes once a day on two days a week for a total of 18 sessions. The control group received a plain adhesive patch placed on the same acupoint. FINDINGS: Both groups showed statistically significant improvements but there were no differences between groups, while a relatively large decrease in pruritus scores was found in the thermal therapy group (P < 0.001) as compared with the non-thermal therapy group. Serum calcium level decreased statistically significantly in the thermal therapy group and was statistically significantly different from that of the control group. CONCLUSION: The lack of effect does not necessarily demonstrate that thermal therapy is not effective or has no therapeutic benefits for uremic pruritus in patients having haemodialysis. Further investigation is warranted, with larger samples and longer intervention.

Using the maternal-fetal genotype incompatibility test to assess non-inherited maternal HLA-DRB1 antigen coding alleles as rheumatoid arthritis risk factors.

Non-inherited maternal antigens encoded by specific HLA-DRB1 alleles (NIMA) have been implicated as a rheumatoid arthritis (RA) risk factor. Using genotype data from North American Rheumatoid Arthritis Consortium study participants and the maternal-fetal genotype incompatibility (MFG) test, we find evidence for offspring allelic effects but no evidence for NIMA as a RA risk factor. We discuss possible reasons why our result conflicts with several previous studies (including one of our own) that used RA patients from northern Europe.