Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

Advances in Bioresorbable Triboelectric Nanogenerators.

With the growing demand for next-generation health care, the integration of electronic components into implantable medical devices (IMDs) has become a vital factor in achieving sophisticated healthcare functionalities such as electrophysiological monitoring and electroceuticals worldwide. However, these devices confront technological challenges concerning a noninvasive power supply and biosafe device removal. Addressing these challenges is crucial to ensure continuous operation and patient comfort and minimize the physical and economic burden on the patient and the healthcare system. This Review highlights the promising capabilities of bioresorbable triboelectric nanogenerators (B-TENGs) as temporary self-clearing power sources and self-powered IMDs. First, we present an overview of and progress in bioresorbable triboelectric energy harvesting devices, focusing on their working principles, materials development, and biodegradation mechanisms. Next, we examine the current state of on-demand transient implants and their biomedical applications. Finally, we address the current challenges and future perspectives of B-TENGs, aimed at expanding their technological scope and developing innovative solutions. This Review discusses advancements in materials science, chemistry, and microfabrication that can advance the scope of energy solutions available for IMDs. These innovations can potentially change the current health paradigm, contribute to enhanced longevity, and reshape the healthcare landscape soon.

OLED catheters for inner-body phototherapy: A case of type 2 diabetes mellitus improved via duodenal photobiomodulation.

Phototherapeutics has shown promise in treating various diseases without surgical or drug interventions. However, it is challenging to use it in inner-body applications due to the limited light penetration depth through the skin. Therefore, we propose an organic light-emitting diode (OLED) catheter as an effective photobiomodulation (PBM) platform useful for tubular organs such as duodenums. A fully encapsulated highly flexible OLED is mounted over a round columnar structure, producing axially uniform illumination without local hotspots. The biocompatible and airtight OLED catheter can operate in aqueous environments for extended periods, meeting the essential requirements for inner-body medical applications. In a diabetic Goto-Kakizaki (GK) rat model, the red OLED catheter delivering 798 mJ of energy is shown to reduce hyperglycemia and insulin resistance compared to the sham group. Results are further supported by the subdued liver fibrosis, illustrating the immense potential of the OLED-catheter-based internal PBM for the treatment of type 2 diabetes and other diseases yet to be identified.

Enhancement of TRP Gene Expression and UV Absorption by Bioconverted Chestnut Inner Shell Extracts Using Lactiplantibacillus plantarum.

In this work, the suppression of tyrosinase-related genes, including an improvement in UV absorption effects of bioconverted CS extracts (BCS), was investigated to improve the skin-whitening effect. Total polyphenols and total flavonoids, which are bioactive components, increased 2.6- and 5.4-times in bioconversion using Lactiplantibacillus plantarum SM4, respectively, as compared to ultrasound-assisted extracts (UCS). The effect of BCS on radical scavenging activity, UV-A absorption, and tyrosinase activity inhibition, contributing to skin-whitening, were 1.3-, 1.2-, and 1.2-times higher than those of UCS, respectively. The main component identified in high-performance liquid chromatography (HPLC) was gallic acid in both UCS and BCS, which increased by 2.9-times following bioconversion. The gene expression of tyrosinase-related proteins, including TRP-1 and TRP-2 genes, was studied to confirm the suppression of melanin synthesis by BCS in order to identify the skin-whitening mechanism, and BCS decreased both genes' expression by 1.7- and 1.6-times, demonstrating that BCS effectively suppressed melanin synthesis. These findings imply that the chestnut inner shell can be employed as a cosmetic material by simultaneously inhibiting melanogenesis and enhancing UV-A absorption through bioconversion using L. plantarum SM4.

Production of Bioactive Substances to Alleviates Hangover and Ethanol-Induced Liver Damage through Fermentation of Oenanthe javanica Using Lactiplantibacillus plantarum.

The purpose of this study is to evaluate the effect of the bioconversion products of Oenanthe javanica extract fermented by Lactiplantibacillus plantarum (OEFL) on relieving hangovers and improving liver function. In addition, the bioactive substance of the OEFL, which alleviates hangover and ethanol-induced liver damage, was identified and its bioactive property was verified through in vivo experiments. In major substances analysis using high-performance liquid chromatography, OEFL produced 9.5-fold higher p-coumaric acid than the O. Javanica extract (OE). In addition, considering that quinic acid, which is not present in the OE, was produced in the OEFL it was confirmed that chlorogenic acid was decomposed into quinic acid by bioconversion. In the in vivo experiment using Sprague-Dawley rats, the OEFL and p-coumaric acid diets reduced blood ethanol, acetaldehyde, GPT, and ALP concentrations, increasing blood albumin concentrations compared to ethanol-administered groups, demonstrating that OEFL and p-coumaric acid, the main substance in the OEFL, improved ethanol-induced liver damage. Furthermore, the OEFL and its main bioactive substance, p-coumaric acid, alleviated liver fibrosis by downregulating TGF-ß, SMAD-2, SMAD-4, α-SMA, and upregulating MMP-1. Therefore, OEFL is expected to be used as a functional food or pharmaceutical material as it has been confirmed to effectively relieve hangovers, prevent liver damage, and delay liver fibrosis in ethanol-induced liver damages.

Salvianolic Acid B Inhibits Hand-Foot-Mouth Disease Enterovirus 71 Replication through Enhancement of AKT Signaling Pathway.

Hand, foot, and mouth disease (HFMD) is caused by enterovirus 71 (EV71) in infants and children under six years of age. HFMD is characterized by fever, mouth ulcers, and vesicular rashes on the palms and feet. EV71 also causes severe neurological manifestations, such as brainstem encephalitis and aseptic meningitis. Recently, frequent outbreaks of EV71 have occurred in the Asia-Pacific region, but currently, no effective antiviral drugs have been developed to treat the disease. In this study, we investigated the antiviral effect of salvianolic acid B (SalB) on EV71. SalB is a major component of the Salvia miltiorrhiza root and has been shown to be an effective treatment for subarachnoid hemorrhages and myocardial infarctions. HeLa cells were cultured in 12-well plates and treated with SalB (100 or 10 µg/ml) and 106 PFU/ml of EV71. SalB treatment (100 µg/ml) significantly decreased the cleavage of the eukaryotic eIF4G1 protein and reduced the expression of the EV71 capsid protein VP1. In addition, SalB treatment showed a dramatic decrease in viral infection, measured by immunofluorescence staining. The Akt signaling pathway, a key component of cell survival and proliferation, was significantly increased in EV71-infected HeLa cells treated with 100 µg/ml SalB. RT-PCR results showed that the mRNA for anti-apoptotic protein Bcl-2 and the cell cycle regulator Cyclin-D1 were significantly increased by SalB treatment. These results indicate that SalB activates Akt/PKB signaling and inhibits apoptosis in infected HeLa cells. Taken together, these results suggest that SalB could be used to develop a new therapeutic drug for EV71-induced HFMD.

Lipid and unsaturated fatty acid productions from three microalgae using nitrate and light-emitting diodes with complementary LED wavelength in a two-phase culture system.

In this study, Pavlova lutheri, Chlorella vulgaris, and Porphyridium cruentum were cultured using modified F/2 media in a 1 L flask culture. Various nitrate concentrations were tested to determine an optimal nitrate concentration for algal growth. Subsequently, the effect of light emitted at a specific wavelength on biomass and lipid production by three microalgae was evaluated using various wavelengths of light-emitting diodes (LED). Biomass production by P. lutheri, C. vulgaris, and P. cruentum were the highest with blue, red, and green LED wavelength with 1.09 g dcw/L, 1.23 g dcw/L, and 1.28 g dcw/L on day 14, respectively. Biomass production was highest at the complementary LED wavelength to the color of microalgae. Lipid production by P. lutheri, C. vulgaris, and P. cruentum were the highest with yellow, green, and red LEDs' wavelength, respectively. Eicosapentaenoic acid production by P. lutheri, C. vulgaris, and P. cruentum was 10.35%, 10.14%, and 14.61%, and those of docosahexaenoic acid were 6.09%, 8.95%, and 11.29%, respectively.

Use of complementary and alternative medicine by lymphoma survivors in South Korea.

PURPOSE: We aimed to examine the experience of complementary and alternative medicine (CAM) use and its association with health-related quality of life (HRQOL) in lymphoma survivors in South Korea. METHODS: The participants were 869 lymphoma survivors from three hospitals in South Korea, all diagnosed with lymphoma at least 24 months prior to participation. Self-reported questionnaires were used to assess CAM use. The questionnaire addressed types of CAM used, sources of information about CAM, reason for CAM use, satisfaction with CAM use, discussion of CAM use with doctors, experience of side effects, costs of CAM use, and intentions to continue using CAM. HRQOL was measured with the EORTC QLQ-C30. RESULTS: Of the 869 participants, 42.2% had experience using CAM, and there were statistically significant differences among CAM users and non-users in terms of sex, religion, and time since diagnosis. A special diet (e.g., ginseng, chitosan, mixed cereals) was the most commonly used type of CAM, and most CAM users (82.1%) were satisfied with their CAM use. Most CAM users (77.5%) did not discuss the use of CAM with their doctors, and only 9.2% reported any side effects from CAM. CAM users showed significantly lower HRQOL scores than did non-users. CONCLUSION: A significant number of lymphoma survivors in Korea have used CAM, and most CAM users are satisfied with their CAM use. Oncology nurses should be aware of the range of CAM use among patients and reflect their responses in their treatment and/or follow-up care.

High Consumption of Iron Exacerbates Hyperlipidemia, Atherosclerosis, and Female Sterility in Zebrafish via Acceleration of Glycation and Degradation of Serum Lipoproteins.

Elevated serum iron level is linked with an increased risk of diabetes and atherosclerosis. However, the pathological mechanism by which iron affects serum lipoprotein levels is unknown. To elucidate the mechanism, a high dose of ferrous ion was applied (final 60 µM, 120 µM) to human serum lipoproteins, macrophages, and human dermal fibroblast (HDF) cells. Iron-treated lipoproteins showed loss of antioxidant ability along with protein degradation and multimerization, especially co-treatment with fructose (final 10 mM). In the presence of fructose, HDF cells showed 3.5-fold more severe cellular senescence, as compared to the control, dependent on the dosage of fructose. In macrophages, phagocytosis of acetylated low-density lipoprotein (acLDL) was more accelerated by ferrous ion, occurring at a rate that was up to 1.8-fold higher, than acLDL alone. After 24 weeks supplementation with 0.05% and 0.1% ferrous ion in the diet (wt/wt), serum total cholesterol (TC) level was elevated 3.7- and 2.1-fold, respectively, under normal diet (ND). Serum triglyceride (TG) was elevated 1.4- and 1.7-fold, respectively, under ND upon 0.05% and 0.1% ferrous ion supplementation. Serum glucose level was elevated 2.4- and 1.2-fold under ND and high cholesterol diet (HCD), respectively. However, body weight was decreased by the Fe2+ consumption. Iron consumption caused severe reduction of embryo laying and reproduction ability, especially in female zebrafish via impairment of follicular development. In conclusion, ferrous ion treatment caused more pro-atherogenic, and pro-senescence processes in human macrophages and dermal cells. High consumption of iron exacerbated hyperlipidemia and hyperglycemia as well as induced fatty liver changes and sterility along with reduction of female fertility.

The effects of laughter therapy on mood state and self-esteem in cancer patients undergoing radiation therapy: a randomized controlled trial.

BACKGROUND: To investigate whether laughter therapy lowers total mood disturbance scores and improves self-esteem scores in patients with cancer. DESIGN/SETTING: Randomized controlled trial in a radio-oncology outpatient setting. PATIENTS: Sixty-two patients were enrolled and randomly assigned to the experimental group (n=33) or the wait list control group (n=29). INTERVENTIONS: Three laughter therapy sessions lasting 60 minutes each. OUTCOME MEASURES: Mood state and self-esteem. RESULTS: The intention-to-treat analysis revealed a significant main effect of group: Experimental group participants reported a 14.12-point reduction in total mood disturbance, while the wait list control group showed a 1.21-point reduction (p=0.001). The per-protocol analysis showed a significant main effect of group: The experimental group reported a 18.86-point decrease in total mood disturbance, while controls showed a 0.19-point reduction (p<0.001). The self-esteem of experimental group was significantly greater than that of the wait list control group (p=0.044). CONCLUSIONS: These results indicate that laughter therapy can improve mood state and self-esteem and can be a beneficial, noninvasive intervention for patients with cancer in clinical settings.

Disparate roles of zinc in chemical hypoxia-induced neuronal death.

Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

Effects of meditation on anxiety, depression, fatigue, and quality of life of women undergoing radiation therapy for breast cancer.

OBJECTIVE: To investigate the effects of meditation on anxiety, depression, fatigue, and quality of life in women who are receiving radiation therapy for breast cancer. DESIGN: Randomized, non-program controlled, parallel intervention clinical trial. SETTING: The ASAN Cancer Center located in Seoul, Korea. INTERVENTION: The subjects of this study included 102 female breast cancer patients who had undergone breast-conserving surgery; these female patients were randomized into equally assigned meditation control groups, with each group consisting of 51 patients. The test group received a total of 12 meditation therapy sessions during their 6-week radiation therapy period, and the control group underwent only a conventional radiation therapy. OUTCOME: The tools used to evaluate the effects of meditation were Hospital Anxiety and Depression scale, Revised Piper Fatigue scale, and European Organization for Research and Treatment of Cancer-Quality of Life Core-30. The results were analyzed based on the principles of intention-to-treat analysis, and, as a corollary analysis, per-protocol analysis was conducted. RESULTS: The breast cancer patients who received meditation therapy compared with the non-intervention group saw improvements in reduction of anxiety (p=.032), fatigue (p=.030), and improvement in global quality of life (p=.028). CONCLUSIONS: Based on the results of this study, an affirmation can be made that meditation can be used as a non-invasive intervention treatment for improving fatigue, anxiety, quality of life, and emotional faculties of women with breast cancer.

Comparison of three tocopherol analogs as an inhibitor of production of proinflammatory mediators in macrophages.

Anti-inflammatory effects of tocopherol (TOL) analogs have been attributed to their potent antioxidant activities. However, we and others have separately reported that γTOL or α-tocopheryl succinate (αTOS), despite their lower antioxidant activities, inhibit lipopolysaccharide (LPS)-induced production of prostaglandin E(2) (PGE(2)) in macrophages and lung epithelial cells more effectively than αTOL. In the present study, we sought to directly analyze the effect of three TOL analogs (αTOL, αTOS, and γTOL) on LPS-induced production of pro-inflammatory mediators in macrophages. Our data demonstrated that the inhibitory effects of all three TOL analogs on nitric oxide production were very limited. In contrast, αTOS dose-dependently and significantly inhibited LPS-induced PGE(2) production in both RAW264.7 cells and peritoneal macrophages, whereas αTOL and γTOL were much less effective. Although αTOS had no effect on LPS-induced cyclooxygenase-2 expression, it did inhibit COX activity in intact cells. αTOS in combination with sulforaphane, a compound that blocked LPS-induced COX-2 expression, cooperatively and more significantly inhibited PGE(2) production. These findings suggest that αTOS is a more potent inhibitor of the pro-inflammatory mediator PGE(2). The inclusion of αTOS in vitamin supplements may further enhance the effectiveness of strategies for preventing diseases associated with inflammation.

Barley intake induces bile acid excretion by reduced expression of intestinal ASBT and NPC1L1 in C57BL/6J mice.

To investigate the hypocholesterolemic mechanism of barley in vivo, six-week-old C57BL/6J mice were fed a high-fat diet (HFD) or high-fat diet containing barley (HFD-B) for seven weeks. Total and LDL cholesterol concentrations were significantly reduced in the HFD-B group while fecal cholesterol and bile acid was increased. Real-time PCR and immunoblot analysis revealed the induction of FXR expression, which in turn suppressed the expression of ASBT and NPC1L1 in the HFD-B group compared with the controls. In the liver, the expression of HMG-CoA reductase was significantly reduced while LDL receptor expression was unaltered in the HFD-B group compared with the controls. Our data suggest that the hypocholesterolemic effects of barley are primarily the result of reduced dietary cholesterol uptake and bile acid resorption. Reduced expression of intestinal ASBT and NPC1L1 may play a key role in the regulation of dietary cholesterol and bile acid metabolism in mice consuming a diet containing barley.

Effects of glucose supplementation on the pharmacokinetics of intravenous chlorzoxazone in rats with water deprivation for 72 h.

It was reported that in rats with water deprivation for 72 h with food (dehydration rat model), the expression of CYP2E1 was 3-fold induced with an increase in mRNA level and glucose supplementation instead of food during 72-h water deprivation (dehydration rat model with glucose supplementation) inhibited the CYP2E1 induction in dehydration rat model. It was also reported that chlorzoxazone (CZX) is metabolized to 6-hydroxychlorzoxazone (OH-CZX) mainly via CYP2E1 in rats. Hence, the effects of glucose supplementation on the pharmacokinetics of CZX and OH-CZX were investigated after intravenous administration of CZX at a dose of 25 mg/kg to control male Sprague-Dawley rats and dehydration rat model and dehydration rat model with glucose supplementation. Based on the above mentioned results of CYP2E1, it could be expected that increased formation of OH-CZX in dehydration rat model could decrease in dehydration rat model with glucose supplementation. This was proven by the following results. In dehydration rat model with glucose supplementation, the AUC of OH-CZX was significantly smaller (1900 versus 1050 microg min/ml), AUC(OH-CZX)/AUC(CZX) ratio was considerably smaller (105 versus 34.3%), C(max) was significantly lower (20.6 versus 8.08 microg/ml), total amount excreted in 24-h urine as unchanged OH-CZX was significantly smaller (62.3 versus 42.7% of intravenous dose of CZX), and in vitro V(max) (2.18 versus 1.20 nmol/min/mg protein) and CL(int) (0.0285 versus 0.0171 ml/min/mg protein) were significantly slower than those in dehydration rat model.

Enhanced anticancer efficacy of alpha-tocopheryl succinate by conjugation with polyethylene glycol.

Alpha-tocopheryl polyethylene glycol succinate (TPGS) has been used to enhance the bioavailability of poorly absorbed drugs and as a vehicle for drug delivery systems. In response to recent reports that alpha-tocopheryl succinate (TOS) acts as an anticancer agent, we investigated whether its polyethylene glycol (PEG) conjugate, TPGS, also possesses anticancer activity. TPGS inhibited the growth of human lung carcinoma cells implanted in nude mice, and in an in vitro cell culture, even more potently than TOS. The time-dependent uptake of TPGS into cells did not differ from that of TOS, indicating that the enhanced antitumor efficacy of TPGS was not due to its increased uptake into cells. Compared with TOS, TPGS was more effective at inducing apoptosis and the generation of reactive oxygen species, suggesting that the superior anticancer efficacy of TPGS is associated with its increased ability to induce apoptosis. Our data suggest that further studies assessing the potential usefulness of TPGS in cancer therapeutics are warranted, since its use as a vehicle in the formulation of anticancer drugs may provide an effective way to improve their therapeutic efficacy.

Potentiation by alpha-tocopheryl succinate of the etoposide response in multidrug resistance protein 1-expressing glioblastoma cells.

Multidrug resistance protein 1 (MRP1) is one of the representative members of the ATP-binding cassette superfamily of transporters that is involved in resistance to chemotherapeutic agents in cancer patients. MRP1 functions as an efflux pump of drugs, primarily those conjugated to glutathione (GSH). Decreases in the intracellular concentration of GSH have been shown to enhance the response of MRP1-overexpressing cells to MRP1-substrate drugs by limiting the available drug-GSH conjugates. We report here that alpha-tocopheryl succinate (TOS), a vitamin E analogue, decreased intracellular GSH concentration and blocked MRP1 function in glioblastoma cells. Functional blockade by TOS of MRP1 was confirmed by the enhanced accumulation of etoposide (VP-16), an MRP1-substrate drug. As a result, co-treatment of TOS with VP-16 or treatment with liposomes containing both TOS and VP-16 greatly enhanced the response of MRP1-expressing glioblastoma cells to VP-16. TOS may be a promising adjuvant for enhancing the therapeutic efficacy of VP-16 in patients with MRP1-expressing glioblastomas.

Deoxypodophyllotoxin, a naturally occurring lignan, inhibits the passive cutaneous anaphylaxis reaction.

This study examined the effect of a podophyllotoxin derivative, deoxypodophyllotoxin (anthricin), which is a medicinal herb product isolated from Anthriscus sylvestris Hoffm. Deoxypodophyllotoxin was tested in a rat PCA (passive cutaneous anaphylaxis) assay by administering deoxypodophyllotoxin intraperitoneally (1.0 to 10 mg/kg, i.p.) and intravenously (0.25 to 1.0 mg/kg, i.v.). Deoxypodophyllotoxin dose-dependently inhibited the PCA reaction activated by anti-dinitrophenyl (DNP) IgE. The PCA inhibitory activity of deoxypodophyllotoxin was stronger than those of prednisolone and indomethacin, which were used as positive controls. These results suggest that deoxypodophyllotoxin may be beneficial in regulating the immediate-type allergic reaction.