Magnetically Stimulated Integrin Binding Alters Cell Polarity and Affects Epithelial-Mesenchymal Plasticity in Metastatic Cancer Cells.

Inorganic nanoparticles (NPs) have been widely recognized for their stability and biocompatibility, leading to their widespread use in biomedical applications. Our study introduces a novel approach that harnesses inorganic magnetic nanoparticles (MNPs) to stimulate apical-basal polarity and induce epithelial traits in cancer cells, targeting the hybrid epithelial/mesenchymal (E/M) state often linked to metastasis. We employed mesocrystalline iron oxide MNPs to apply an external magnetic field, disrupting normal cell polarity and simulating an artificial cellular environment. These led to noticeable changes in the cell shape and function, signaling a shift toward the hybrid E/M state. Our research suggests that apical-basal stimulation in cells through MNPs can effectively modulate key cellular markers associated with both epithelial and mesenchymal states without compromising the structural properties typical of mesenchymal cells. These insights advance our understanding of how cells respond to physical cues and pave the way for novel cancer treatment strategies. We anticipate that further research and validation will be instrumental in exploring the full potential of these findings in clinical applications, ensuring their safety and efficacy.

Comprehensive workflow encompassing discovery, verification, and quantification of indicator peptide in snail mucin using LC-quadrupole Orbitrap high-resolution tandem mass spectrometry.

Peptidomics analysis was conducted using high-resolution tandem mass spectrometry (MS2) to determine the peptide profile of snail-derived mucin extract (SM). The study was also aimed to identify an indicator peptide and validate a quantification method for this peptide. The peptide profiling and identification were conducted using discovery-based peptidomics analysis employing data-dependent acquisition, whereas the selected peptides were verified and quantified using parallel reaction monitoring acquisition. Among the 16 identified peptides, the selected octapeptide (TEAPLNPK) was quantified via precursor ion ionization (m/z 435.2400), followed by quantification of the corresponding quantifier ion fragment (m/z 639.3824) using MS2. The quantification method was optimized and validated in terms of specificity, linearity, accuracy, precision, and limit of detection/quantification. The validated method accurately quantified the TEAPLNPK content in the SM as 7.5 ± 0.2 µg/g. Our study not only identifies an indicator peptide from SM but also introduces a novel validation method, involving precursor ion ionization and quantification of specific fragments. Our findings may serve as a comprehensive workflow for the monitoring, selection, and quantification of indicator peptides from diverse food resources.

ROS-responsive PEGylated ferrocene polymer nanoparticles with improved stability for tumor-selective chemotherapy and imaging.

Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their biomedical applications remain limited due to their poor physiological stability. PEGylation of nanocarriers improves their stability and biocompatibility. In this study, we aimed to develop novel PEG-ferrocene nanoparticles (PFNPs) with enhanced stability and ROS responsiveness for the delivery of paclitaxel (PTX) and imaging agents. PEGylation improved the stability of ferrocene nanoparticles, inhibiting their ROS-responsive destruction. Several PEG-ferrocene polymers containing different molar ratios of methacrylic acid and poly (ethylene glycol) methyl ether methacrylate was designed for optimization. ROS-responsive polymers with optimal monomer ratios were self-assembled into PFNPs with enhanced stability. The PFNPs distended, effectively releasing encapsulated PTX and imaging agents within 8 h in the presence of ROS. Furthermore, they remained stable, with no changes in their hydrodynamic diameters or polydispersity indexes after storage in an aqueous solution and biological buffer. The accumulation of PFNPs in a tumor model in vivo was 15-fold higher than a free dye. PTX-loaded PFNPs showed a substantial tumor-suppression effect, reducing tumor size to approximately 18% of that in the corresponding control group. These findings suggest a promising application of ROS-responsive PFNPs in tumor treatment as biocompatible nanocarriers of anticancer drugs and imaging agents.

Antioxidant and Anti-Inflammatory Activities of Sargassum macrocarpum Extracts.

Oxidative stress and the inflammatory response are known to be the most important pathological factors for aging skin cells. Therefore, substances that protect skin cells from oxidative stress and inflammatory reactions of the skin have potential as functional ingredients for skin care. In the present study, we investigated the potential of Sargassum macrocarpum as an anti-inflammatory candidate for inflammatory skin disease. Antioxidant and anti-inflammatory activities are desirable properties in such functional materials. The total polyphenol content as well as antioxidant and anti-inflammatory activities were evaluated in hot-water (HES) and ethanol (EES) extracts of S. macrocarpum. The polyphenol content was higher in the HES (HES: 115.9 ± 15.3 mg GA/g, EES: 3.9 ± 0.5 mg GA/g), and the HES also had ABTS (HES: IC50 1.0 ± 0.0 mg/mL, EES: IC50 16.09 ± 0.7 mg/mL) and DPPH (HES: IC50 6.50 ± 0.3 mg/mL, EES: IC50 35.3 ± 3.1 mg/mL) radical scavenging capacities as well as FRAP activity (HES: IC50 18.8 ± 0.4 mg/mL, EES: IC50 n.d.). Compared with the EES at the equivalent concentration range (1.25-20 µg/mL), the HES exerted a more potent inhibitory activity on LPS-stimulated nitric oxide (10.3-43.1%), IL-6 (15.7-45.0%), and TNF-α (14.1-20.8%) in RAW 264.7 macrophage cells in addition to TNF-α and IFN-γ-facilitated IL-6 (10.9-84.1%) and IL-8 (7.7-73.2%) in HaCaT keratinocytes. These results suggested that water-soluble materials might be deeply involved in the antioxidant and anti-inflammatory activity in S. macrocarpum. General composition analysis indicated that the HES contains more carbohydrates and polyphenols than the EES, and the monosaccharide composition analysis suggested that fucose-containing sulfated polysaccharide and ß-glucan might be potent anti-inflammatory candidates in the HES. The present study presents important preliminary results and a valuable strategy for developing novel anti-skin dermatitis candidates using a hot-water extract of S. macrocarpum.

Perfluorooctylbromide-loaded fucoidan-chlorin e6 nanoparticles for tumor-targeted photodynamic therapy.

Efficient delivery of a photosensitizer (PS) and oxygen to tumor tissue is critical for successful photodynamic therapy (PDT). For this purpose, we developed a fucoidan (Fu)-chlorin e6 (Ce6) nanoparticle (NP) containing perfluorooctylbromide (PFOB). Fu, a biopolymer derived from seaweed, made up the hydrophilic shell of the NP and provided specific targeting to tumor cells by P-selectin binding. Conjugation with the hydrophobic Ce6 enabled self-assembly and Ce6-generated cytotoxic reactive oxygen species to kill tumor cells upon laser irradiation. PF supplied oxygen to the hypoxic tumor tissue and increased the efficacy of the PDT. The developed Fu-Ce6-PF-NPs bound specifically to SCC7 tumor cells and killed them via a photodynamic effect on laser irradiation. High accumulation of the NPs in tumor tissue and improved tumor suppression by PDT were observed in SCC7 tumor-bearing mice. The overall data demonstrated the potential of Fu-Ce6-PF-NP as a tumor-targeting drug carrier for effective PDT.

Immunostimulatory Effect of Postbiotics Prepared from Phellinus linteus Mycelial Submerged Culture via Activation of Spleen and Peyer's Patch in C3H/HeN Mice.

Medicinal mushrooms are an important natural resource promoting health benefits. Herein, Phellinus linteus mycelia were prepared under submerged cultivation, the mycelium-containing culture broth was extracted as a whole to obtain the postbiotic materials (PLME), and its effect on the immune system was evaluated in normal C3H/HeN mice. Oral administration of PLME for 4 weeks was well tolerated and safe. In the PLME-administered groups, in addition to the production of immunostimulatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), the mitogenic activity was significantly increased. PLME administration also significantly increased the levels of serum immunoglobulin G (IgG) and IgA in the small intestinal fluid and Peyer's patches and enhanced Peyer's patch-mediated bone marrow cell proliferation activity and cytokine production (IL-2, IL-6, and IFN-γ). Histomorphometric analyses showed an increase in immune cells in the spleen and small intestinal tissues of mice administered PLME, supporting the rationale for its immune system activation. PLME mainly contained neutral sugar (969.1 mg/g), comprising primarily of glucose as a monosaccharide unit. The ß-glucan content was 88.5 mg/g. Data suggest that PLME effectively promote immune function by stimulating the systemic immune system through the spleen and intestinal immune tissues. PLME can thus be developed as a functional ingredient to enhance immune functions.

Functional Constipation and Anorexia in Community-Dwelling Older Adults: Korean Frailty and Aging Cohort Study (KFACS).

Anorexia is a relevant geriatric syndrome because it accounts for most malnutrition in older adults. Constipation has been suggested as a risk factor for anorexia. This study aimed to examine the association between anorexia and functional constipation in community-dwelling older adults. Data on 899 subjects aged 72-86 years were obtained from a follow-up survey of the Korean Frailty and Aging Cohort Study in 2018. Anorexia was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ), while functional constipation was diagnosed based on Rome IV criteria. Anorexia and functional constipation were present in 30.9% and 19.6% of the participants, respectively. Age, female sex, chewing problems, malnutrition, polypharmacy, low Mini-Mental Status Examination (MMSE) score, depressed mood, low serum albumin, and functional constipation were associated with anorexia in the univariate analysis. In the multivariate logistic regression, functional constipation was associated with anorexia (OR 1.478, 95% CI 1.038-2.104) after adjusting for age, female sex, and MMSE score. However, after further adjusting for depressed mood (OR 2.568) and chewing problems (OR 2.196), the relationship was no longer significant. This study showed that functional constipation is associated with anorexia in community-dwelling older adults, but this association is confounded by depressed mood and chewing problems.

Older Men Living with Spouse and Older Women Living with Spouse and Children Have Lower Frailty Prevalence: The Korean Frailty and Aging Cohort Study (KFACS).

BACKGROUND: In older adults, the risk of frailty is higher among those who are unmarried than among those who are married. However, no study has reported about the relationship between cohabitation status and frailty. METHODS: This cross-sectional study included 2,128 community-dwelling adults aged between 70 and 84 years who underwent interviews and physical function assessments for the Korean Frailty and Aging Cohort Study. The definition of frailty was derived from the Fried frailty phenotype. Cohabitation was categorized as "living alone", "with spouse only", "with children only", and "with spouse and children". RESULTS: The mean age was 76 years, and 46.3% of the adults were men. After adjusting for age, education, income, nutritional status, alcohol, smoking history, Geriatric Depression Scale, Mini-Mental State Examination, Korean Activities of Daily Living, Korean Instrumental Activities of Daily Living, urinary incontinence, and polypharmacy, the odds ratios of frailty were 0.323 (95% confidence interval [CI], 0.137-0.763; p<0.001) and 1.089 (95% CI, 0.671-1.769; p=0.730) for men and women living with a spouse, respectively. The odds ratios of frailty were 0.329 (95% CI, 0.117-0.927; p=0.035) and 0.332 (95% CI, 0.123-0.891; p=0.029) for men and women living with spouse and children, respectively. CONCLUSION: Men living with a spouse or with a spouse and children had a lowered prevalence of frailty, and women living with a spouse and children together had a lowered prevalence of frailty.