Cytotoxicity and Multi-Enzyme Inhibition of Nepenthes miranda Stem Extract on H838 Human Non-Small Cell Lung Cancer Cells and RPA32, Elastase, Tyrosinase, and Hyaluronidase Proteins.

The carnivorous pitcher plants of the genus Nepenthes have long been known for their ethnobotanical applications. In this study, we prepared various extracts from the pitcher, stem, and leaf of Nepenthes miranda using 100% ethanol and assessed their inhibitory effects on key enzymes related to skin aging, including elastase, tyrosinase, and hyaluronidase. The cytotoxicity of the stem extract of N. miranda on H838 human lung carcinoma cells were also characterized by effects on cell survival, migration, proliferation, apoptosis induction, and DNA damage. The cytotoxic efficacy of the extract was enhanced when combined with the chemotherapeutic agent 5-fluorouracil (5-FU), indicating a synergistic effect. Flow cytometry analysis suggested that the stem extract might suppress H838 cell proliferation by inducing G2 cell cycle arrest, thereby inhibiting carcinoma cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 15 most abundant compounds in the stem extract of N. miranda. Notably, the extract showed a potent inhibition of the human RPA32 protein (huRPA32), critical for DNA replication, suggesting a novel mechanism for its anticancer action. Molecular docking studies further substantiated the interaction between the extract and huRPA32, highlighting bioactive compounds, especially the two most abundant constituents, stigmast-5-en-3-ol and plumbagin, as potential inhibitors of huRPA32's DNA-binding activity, offering promising avenues for cancer therapy. Overall, our findings position the stem extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and anti-skin-aging treatments, warranting further investigation into its molecular mechanisms and potential clinical applications.

Factors Contributing to Non-Concordance Between End-of-Life Care and Advance Care Planning.

CONTEXT: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life. OBJECTIVES: To examine factors contributing to nonconcordance between end-of-life care and advance care planning. METHODS: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention. An instrument with eight items contributing to non-concordant care, developed through literature review and experts' consensus, was employed. An expert panel reviewed electronic medical records to determine factors associated with non-concordant care for each patient. Statistical analysis, including descriptive statistics and the chi-square test, examines demographic characteristics, and associations. RESULTS: Among the enrolled 7871 patients, 97 (1.2%) received non-concordant care. The most prevalent factor was "families being too distressed about the patient's deteriorating condition and therefore being unable to let go" (84.5%) followed by "limited understanding of medical interventions among patients and surrogates" (38.1%), and "lack of patient participation in the decision-making process" (25.8%). CONCLUSIONS: This study reveals that factors related to relational autonomy, emotional support, and health literacy may contribute to non-concordance between advance care planning and end-of-life care. In the future, developing an advance care planning model emphasizes respecting relational autonomy, providing emotional support, and enhancing health literacy could help patients receiving a goal concordant and holistic end-of-life care.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

Electrical cortical stimulation for refractory focal epilepsy: A long-term follow-up study.

OBJECTIVE: To report the long-term seizure control and safety of open-loop electrical cortical stimulation in patients with refractory focal epilepsy of diverse etiologies. METHODS: Six patients who received a therapeutic trial of cortical stimulation were included retrospectively. The frequency of seizures was recorded before and after implantation. Surgical procedure- and stimulation-related adverse effects were also recorded. RESULTS: The mean reductions in seizures were 61% at 1 year, 68% at 2 years, and 80% at 3-7 years post-implantation. The median follow-up time was 54 months (range 36-156 months). The etiologies of epilepsy included polymicrogyria in two patients, post-traumatic in one patient, and periventricular heterotopia, post-encephalitis, and familial lateral temporal lobe epilepsy in the remaining three patients. Status epilepticus stopped immediately after stimulation in three patients with focal status epilepticus or epilepsia partialis continua at baseline, with a long-term reduction in seizures of more than 90% and improvements in conscious level. Tissue incompatibility with the connection wire was noted in one patient, which subsided after the system was removed. CONCLUSIONS: Open-loop cortical stimulation of epileptic foci improved seizure control in our patients with refractory focal epilepsy of diverse etiologies. Electrical cortical stimulation stopped epilepsia partialis continua/focal status epilepticus immediately after the intervention and exhibited a sustained effect in reducing seizures. No procedure-related complications were observed. Further case cohort studies are needed to clarify which patients respond to open-loop cortical stimulation.

Production of bioactive exopolysaccharides from bitter medicinal mushroom, Antrodia camphorata (M. Zang et C.H. Su) Sh.H. Wu et al. (Aphyllophoromycetideae) in submerged cultivation.

This study examines the effects of various fructose concentrations in media on the production and quality of bioactive exopolysaccharides (EPS) from Bitter medicinal mushroom, Antrodia camphorata in submerged cultures. The fructose in media of submerged cultures of A. camphorata significantly affected the production, average molecular weight (Mn), and antioxidant activity of exopolysaccharides. The specific growth rate decreased monotonically from 0.33 to 0.25 1/day as the fructose concentration increased from 10 to 60 g/L; however, maximum production and productivity for EPS increased from 75.23 to 164.87 mg/L and 6.27 to 9.70 mg/L/day, respectively. In addition, the fed-batch culture used in this study significantly improved the production of EPS (2.43-fold enhancement, from 75.23 to 182.99 mg/L), number average molecular weights of EPS (1.47-fold enhancement, from 5.44 x 10, to 7.98 x 10(5) Da), protein/exopolysaccharide ratios (1.63-fold enhancement, from 16% to 26%), and antioxidant activity of EPS (1.32-fold enhancement, from 60% to 79%), as compared with corresponding properties of batch fermentation at 10 g/L fructose in an air-lift bioreactor. The antioxidant activity of EPS was highly correlated with number average molecular weights (R2 = 0.90) and protein/exopolysaccharide ratios (R2 = 0.96). The positive results of this research have successfully verified the promotion efficiency on the production and quality of EPS from the medicinal mushroom A. camphorata.

High cervical spinal cord stimulation after failed dorsal root entry zone surgery for brachial plexus avulsion pain.

BACKGROUND: Many patients had intractable pain after brachial plexus avulsion. This article describes a feasible method of high cervical SCS for a patient who failed in DREZ surgery to treat the pain. CASE DESCRIPTION: A 70-year-old man had right brachial plexus avulsion after a car accident 15 years ago. He complained of chronic spontaneous pain over his right upper limb since then. Two DREZ surgeries failed to relieve the pain. The pain was successfully controlled by high cervical SCS. CONCLUSION: Stimulating the high cervical spinal cord is effective for treating intractable pain after brachial plexus avulsion, which the DREZ surgery failed to relieve.