Effects of Natural Products on Enzymes Involved in Ferroptosis: Regulation and Implications.

Ferroptosis is a form of regulated cell death that is characterized by the accumulation of iron-dependent lipid peroxides. The regulation of ferroptosis involves both non-enzymatic reactions and enzymatic mechanisms. Natural products have demonstrated potential effects on various enzymes, including GPX4, HO-1, NQO1, NOX4, GCLC, and GCLM, which are mainly involved in glutathione metabolic pathway or oxidative stress regulation, and ACSL3 and ACSL4, which mainly participate in lipid metabolism, thereby influencing the regulation of ferroptosis. In this review, we have provided a comprehensive overview of the existing literature pertaining to the effects of natural products on enzymes involved in ferroptosis and discussed their potential implications for the prevention and treatment of ferroptosis-related diseases. We also highlight the potential challenge that the majority of research has concentrated on investigating the impact of natural products on the expression of enzymes involving ferroptosis while limited attention is given to the regulation of enzyme activity. This observation underscores the considerable potential and scope for exploring the influence of natural products on enzyme activity.

Scanning before injection for costochondritis: A case report of ultrasound imaging of Hodgkin's lymphoma with chest wall invasion.

Non-traumatic costochondritis, which manifests as pain and tenderness over the anterior chest wall, may be associated with inflammatory arthritis affecting the upper costochondral and sternocostal joints. Local corticosteroid injection is helpful for recalcitrant cases and ultrasound guidance may not be routinely used by experienced rheumatologists. We report a female patient with pain over the right upper parasternal area with gradual swelling near the first costosternal junction. The ultrasound examination revealed a hyper-vascular mass, which was proven to be Hodgkin's lymphoma. We want to emphasize the importance of using ultrasound for guiding injection for costochondral lesions which facilitated the detection of a tumor invading the chest wall in our case.

Increased heterogeneity of brain perfusion predicts the development of cerebrovascular accidents.

ABSTRACT: The heterogeneity of brain perfusion is related to the risk factors of thromboembolic events such as antiphospholipid syndrome. However, the effectiveness of brain perfusion heterogeneity as a marker to predict thromboembolic events has not been confirmed. Our objective was to evaluate the effectiveness of brain perfusion heterogeneity as a marker to predict the development of cerebrovascular accidents. In this retrospective cohort study, patients who underwent Tc-99m ECD brain SPECT from January 1, 2006 through December 31, 2008 were included. Each study was reoriented with the Talairach space provided by the NeuroGam Software package. Heterogeneity of brain perfusion was measured as the coefficient of variation. The study outcome was the risk of cerebral vascular accidents in patients with increased heterogeneity of brain perfusion between January 1, 2006 and December 31, 2015. A multiple Cox proportional hazards model was applied to evaluate the risk of cerebrovascular accidents. A total of 70 patients were included in this study. The median age was 39 years (range, 28 - 59 years). There were 55 (78.6%) women. For increased heterogeneity of brain perfusion, the hazard ratio of cerebrovascular accidents was 2.68 (95% CI, 1.41 - 5.09; P = .003) after adjusting for age, sex, hypertension, diabetes mellitus, and dyslipidemia. Our study suggests that increased heterogeneity of brain perfusion is associated with an increased risk of cerebrovascular accidents.

Highly sensitive silicon photonic temperature sensor based on liquid crystal filled slot waveguide directional coupler.

A highly sensitive silicon photonic temperature sensor based on silicon-on-insulator (SOI) platform has been proposed and demonstrated. A two-mode nano-slot waveguide device structure cladded with a nematic liquid crystal (LC), E7, was adopted to facilitate strong light-matter interaction and achieve high sensitivity. The fabricated sensor was characterized by measuring the optical transmission spectra at different ambient temperatures. The extracted temperature sensitivities of the E7-filled device are 0.810 nm/°C around room temperature and 1.619 nm/°C near 50°C, which match well with simulation results based on a theoretical analysis. The results obtained represent the highest experimentally demonstrated temperature sensitivity for a silicon-waveguide temperature sensor on SOI platform. The slot waveguide directional coupler device configuration provides submicron one-dimensional spatial resolution and flexible selection in LC materials for designing temperature sensitivity and operational temperature range required by specific applications.

Can ultrasound differentiate acute erosive arthritis associated with osteomyelitis, rheumatoid arthritis, or gouty arthritis?

AIM: The study intended to determine the specific ultrasonographic features of acute arthritis with periarticular bone erosions caused by acute osteomyelitis (OM), rheumatoid arthritis (RA) and gouty arthritis (GA). METHOD: We included 33 patients (seven with acute OM, 18 with RA flares, and eight with GA attacks) having acute monoarthritis or oligoarthritis, and receiving ultrasound (US) examinations in the acute stage. The US images were rated by three rheumatologists blinded to the diagnosis. The median scores of their evaluation of the subcutaneous tissue, periosteum, and synovium were compared. Interrater reliability was calculated using Cronbach's alpha. RESULTS: The highest mean grade of subcutaneous edema appeared in patients with acute OM, and grade 2 edema was more frequent than patients with RA and GA (P = .003 and P = .026, respectively; α = .869). The prevalence of subcutaneous power Doppler signal was also higher in patients with acute OM than in those with RA and GA (P < .001 and P = .041, respectively; α = .756). Periosteal vascularity presented more frequently in acute OM (P = .003 compared with RA; P = .041 compared with GA), but the interrater reliability was poor (α = .518). The tophaceous material in GA was distinctive from OM and RA (P = .010 and P < .001, respectively; α = .774). CONCLUSION: The most discriminative US features in this study were the subcutaneous tissue changes in addition to the periosteal findings. US could contribute to the differential diagnosis of acute erosive arthritis.

Increased heterogeneity of brain perfusion is an early marker of central nervous system involvement in antiphospholipid antibody carriers.

OBJECTIVE: The non-criteria neuropsychiatric manifestations of antiphospholipid syndrome include headache, dizziness, vertigo, seizure, depression and psychosis. There were still no objective methods qualified to detect the early central nervous system involvement in non-criteria antiphospholipid syndrome. We evaluated the effectiveness of Tc-99m ECD SPECT in assessing circulatory insufficiency in the brains of patients with antiphospholipid antibodies and neuropsychiatric symptoms but without thromboembolism. MATERIALS AND METHODS: Patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms composed the case group; patients without antiphospholipid antibody served as the control group. Subjects with a history of thromboembolism or autoantibodies to extractable nuclear antigens were excluded. All patients received Tc-99m ECD SPECT studies and were classified by the number of positive antiphospholipid antibodies they carried. The heterogeneity of brain perfusion was defined as the coefficient of variation of the SPECT signals. Analysis of variance (ANOVA) was applied to evaluate the differences between the groups. RESULTS: Total 60 adult patients were included in this study. There were 54 patients in the case group and 6 patients in the control group. The mean age was 38.3 ± 11.5 years. There were 52 women and 8 men. There was no significant difference in the mean brain perfusion between groups (P = 0.69). However, Tc-99m ECD SPECT demonstrated significant heterogeneity of brain perfusion in relation to the number of antiphospholipid antibodies (P = 0.01). CONCLUSIONS: This is the first study demonstrating that Tc-99m ECD SPECT can early detect the increased heterogeneity of brain circulation in non-criteria antiphospholipid antibody carriers.

Intermediate Molecular Mass Hyaluronan and CD44 Receptor Interactions Enhance Neutrophil Phagocytosis and IL-8 Production via p38- and ERK1/2-MAPK Signalling Pathways.

CD44 is a common leukocyte adhesion molecule expressed on the surface of various cells. Hyaluronan (HA), the natural ligand of CD44, is a simple repeated disaccharide with variable molecular mass that is widely distributed on cell surfaces and the connective tissue matrix. The binding of small molecular mass HA (SMM-HA, MW < 80 kDa) to CD44 on immune-related cells elicits cell proliferation, differentiation, and cytokine production. However, the effects and molecular basis of intermediate molecular mass HA (IMM-HA, MW ≈ 500 kDa)-CD44 interactions on polymorphonuclear neutrophil (PMN) functions have not been elucidated. We hypothesised that IMM-HA would potentiate immune functions as well as SMM-HA. In the present study, we demonstrated IMM-HA and CD44 interactions enhanced normal PMN phagocytosis and IL-8 production compared to those with LPS or anti-CD45 treatment via F-actin cytoskeleton polymerization and subsequent ERK1/2- and p38-MAPK phosphorylation. Antibody-based inhibition of CD44 did not affect PMN function; however, F-actin aggregation was induced without MAPK phosphorylation. Enhanced PMN function via IMM-HA was determined to be CD44-dependent since this effect was abolished in DMSO-induced CD44(-) PMN-like cells obtained from HL-60 cells. In conclusion, we demonstrated that IMM-HA and CD44 interactions on PMNs potently elicit F-actin cytoskeleton polymerization and p38- and ERK1/2-MAPK phosphorylation to enhance PMN function.

Rituximab for refractory digital infarcts and ulcers in systemic sclerosis.

Systemic sclerosis is an uncommon connective tissue disease characterised by excessive deposition of collagen and vasculopathy which affects the skin and multiple internal organs. It is associated with autoimmunity, inflammation, vasculopathy and fibrosis. Managing Raynaud's phenonemon, digital infarcts and ulcers in systemic sclerosis patients is often a challenge particularly among rheumatologists. We report a case of systemic sclerosis patient with refractory digital infarcts and ulcers responded successfully with rituximab.

Autonomic dysfunction because of severe tetanus in an unvaccinated child.

Tetanus is rare in a country with a national vaccination program. When it does occur, the associated autonomic dysfunction is a challenge for physicians. We report here a case of an unvaccinated 5-year-old boy who suffered from tetanus complicated by autonomic dysfunction, which was successfully controlled by the infusion of magnesium sulfate. This is the first case that demonstrated the therapeutic effect of magnesium sulfate in a child with tetanus. This case highlights the importance of implementing a vaccination program.