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2.
Biomed Pharmacother ; 145: 112402, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34773763

RESUMO

PAI-1 and CTGF are overexpressed in kidney diseases and cause fibrosis of the lungs, liver, and kidneys. We used a rat model of unilateral ureteral obstruction (UUO) to investigate whether 6-BIO, a glycogen synthase kinase-3ß inhibitor, attenuated fibrosis by inhibiting PAI-1 and CTGF in vivo. Additionally, TGFß-induced cellular fibrosis was observed in vitro using the human kidney proximal tubular epithelial cells (HK-2), and rat interstitial fibroblasts (NRK49F). Expression of fibrosis-related proteins and signaling molecules such as PAI-1, CTGF, TGFß, αSMA, SMAD, and MAPK were determined in HK-2 and NRK49F cells using immunoblotting. To identify the transcription factors that regulate the expression of PAI-1 and CTGF the promoter activities of AP-1 and SP-1 were analyzed using luciferase assays. Confocal microscopy was used to observe the co-localization of AP-1 and SP-1 to PAI-1 and CTGF. Expression of PAI-1, CTGF, TGFß, and α-SMA increased in UUO model as well as in TGFß-treated HK-2 and NRK49F cells. Furthermore, UUO and TGFß treatment induced the activation of P-SMAD2/3, SMAD4, P-ERK 1/2, P-P38, and P-JNK MAPK signaling pathways. PAI-1, CTGF, AP-1 and SP-1 promoter activity increased in response to TGFß treatment. However, treatment with 6-BIO decreased the expression of proteins and signaling pathways associated with fibrosis in UUO model as well as in TGFß-treated HK-2 and NRK49F cells. Moreover, 6-BIO treatment attenuated the expression of PAI-1 and CTGF as well as the promoter activities of AP-1 and SP-1, thereby regulating the SMAD and MAPK signaling pathways, and subsequently exerting anti-fibrotic effects on kidney cells.

3.
Food Funct ; 12(23): 12161, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34778895

RESUMO

Correction for 'CCL01, a novel formulation composed of Cuscuta seeds and Lactobacillus paracasei NK112, enhances memory function via nerve growth factor-mediated neurogenesis' by In Gyoung Ju et al., Food Funct., 2021, 12, 10690-10699, DOI: 10.1039/D1FO01403J.

4.
Tumori ; : 3008916211059852, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806477

RESUMO

OBJECTIVE: To identify risk factors of primary site necrosis (PSN) after definitive concurrent chemoradiation therapy (CCRT) in patients with nonoral cavity head and neck cancer (HNC). METHODS: We retrospectively reviewed the records of 256 patients treated with CCRT for HNC during 2010-2018. Patient-related (age, sex, history of smoking, hypertension, diabetes mellitus, serum hemoglobin and albumin), tumor-related (tumor site, American Joint Committee on Cancer stage), and treatment-related (induction chemotherapy, maximum point dose and mean dose of planning target volume [PTV] of primary site, absolute volumes of the PTV receiving >50-75 Gy [V50-V75]) variables were analyzed. Critical dosimetric parameters of PSN were identified using receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to select the significant variables for PSN development. RESULTS: After median follow-up of 44 months (range, 5-127), 7 patients (2.7%) developed PSN with a median time to event of 10 months (range, 3-12). V70 ⩾79.8 mL was the most critical dosimetric parameter for PSN (area under the ROC curve 0.873, sensitivity 0.857, specificity 0.747). In univariate analyses, pretreatment serum hemoglobin <11.0 g/dL and V70 ⩾79.8 mL were significantly associated with higher risk of PSN occurrence. V70 ⩾79.8 mL (hazard ratio 5.960, 95% confidence interval 1.289-27.548; p = 0.022) remained significant predictors of PSN in multivariate analyses. CONCLUSIONS: V70 ⩾79.8 mL is significantly related to the risk of developing PSN. These findings offer valuable clues for clinicians to minimize PSN incidence in HNC treated with curative CCRT.

5.
Mater Horiz ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787612

RESUMO

Molecular doping of a polythiophene with oligoethylene glycol side chains is found to strongly modulate not only the electrical but also the mechanical properties of the polymer. An oxidation level of up to 18% results in an electrical conductivity of more than 52 S cm-1 and at the same time significantly enhances the elastic modulus from 8 to more than 200 MPa and toughness from 0.5 to 5.1 MJ m-3. These changes arise because molecular doping strongly influences the glass transition temperature Tg and the degree of π-stacking of the polymer, as indicated by both X-ray diffraction and molecular dynamics simulations. Surprisingly, a comparison of doped materials containing mono- or dianions reveals that - for a comparable oxidation level - the presence of multivalent counterions has little effect on the stiffness. Evidently, molecular doping is a powerful tool that can be used for the design of mechanically robust conducting materials, which may find use within the field of flexible and stretchable electronics.

6.
ACS Biomater Sci Eng ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817170

RESUMO

The self-expanding metal stent (SEMS) is a versatile, palliative treatment method for unresectable, malignant, non-vascular strictures. Colorectal cancer (CRC) is one of the candidates for the application of the SEMS, in combination with the photothermal ablation (PTA) technique that enhances its therapeutic efficacy. The objective of this study was to investigate the efficacy of stent-mediated PTA therapy in an endoscopy-guided, orthotopic rectal cancer model. A total of 30 of 40 mice with the tumor size of grade 4 were included and were divided into three groups of 10 mice each. Group A underwent a gold nanoparticle (AuNP)-coated SEMS but no near-infrared (NIR) irradiation, group B received an uncoated control SEMS with NIR irradiation, and group C received a AuNP-coated SEMS and NIR irradiation together. Colonoscopy and in vivo imaging, immunohistochemical analysis, and quantitative reverse-transcription polymerase chain reaction of major tumor markers were performed. Stent placement and PTA were technically successful using colonoscopy. The tumor grade reduction after PTA is significant in group C, compared with groups A or B (p < 0.001). Molecular analysis validated this observation with a significantly reduced Mapk1 proliferation marker or increased Jnk expression. Histological analysis confirmed the localized PTA therapy using AuNP-coated SEMS profoundly ablated tumor outgrowth through the stent. Our results indicate that this novel strategy of localized PTA therapy could be a promising option for palliative treatment of CRC and to support prolonged stent patency with a decreased tumor volume.

7.
Nanomaterials (Basel) ; 11(11)2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34835584

RESUMO

The heat dissipation of a metal heat sink for passive cooling can be enhanced by surface modifications to increase its thermal emissivity, which is reflected by a darker surface appearance. In this study, copper electrodeposition followed by heat treatment was applied to a copper substrate. The heat treatment formed a nanoporous oxide layer containing CuO and Cu2O, which has a dark blackish color and therefore increased the thermal emissivity of the surface. The heat dissipation performance was evaluated using the sample as a heat sink for an LED module. The surface-treated copper heat sink with a high thermal emissivity oxide layer enhanced the heat dissipation of the LED module and allowed it to be operated at a lower temperature. With an increase in the heat treatment, the thermal emissivity increases to 0.865, but the thermal diffusivity is lower than the copper substrate by ~12%. These results indicate that the oxide layer is a thermal barrier for heat transfer, thus optimization between the oxide thickness and thermal emissivity is required by evaluating heat dissipation performance in operating conditions. In this study, an oxide layer with an emissivity of 0.857 and ~5% lower thermal diffusivity than the copper substrate showed the lowest LED operating temperature.

8.
Sci Rep ; 11(1): 20659, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667205

RESUMO

Gut lactobacilli and bifidobacteria on the immune homeostasis. Therefore, to understand the mechanism in vivo, we selected human fecal Lactobacillus rhamnosus NK210 and Bifidobacterium longum NK219, which strongly suppressed the IFN-γ to IL-10 expression (IIE) ratio in lipopolysaccharide-stimulated macrophages. Thereafter, we examined their effects on the endotoxin, antibiotics, or antitumor drug-stimulated immune imbalance in mice. Intraperitoneal injection of lipopolysaccharide and oral gavage of ampicillin increased IFN-γ and TNF-α expression in the spleen, colon, and hippocampus, while IL-10 expression decreased. However, intraperitoneal injection of cyclophosphamide suppressed IFN-γ, TNF-α, and IL-10 expression. LPS exposure induced splenic natural killer cell cytotoxicity against YAC-1 cells (sNK-C) and peritoneal macrophage phagocytosis against Candida albicans (pMA-P) activities, while cyclophosphamide and ampicillin treatments suppressed sNK-C and pMA-P activities. However, LPS, ampicillin, cyclophosphamide all increased IIE and TNF-α to IL-10 expression (TIE) ratios. Oral administration of NK210 and/or NK219 significantly reduced LPS-induced sNK-C, pMA-P, and IFN-γ expression, while cyclophosphamide- or ampicillin-suppressed sNK-C and pMA-P activities, cyclophosphamide-suppressed IFN-γ, TNF-α, and IL-10 expression, and ampicillin-suppressed IL-10 expression increased. Nevertheless, they suppressed LPS-, ampicillin-, or cyclophosphamide-induced IIE and TIE ratios, cognitive impairment, and gut dysbiosis. In particular, NK219, but not NK210, increased the IIE expression ratio in vitro and in vivo, and enhanced sNK-C and pMA-P activities in normal control mice, while cognitive function and gut microbiota composition were not significantly affected. These findings suggest that NK210, Lactobacillus sp, and NK219, Bifidobacterium additively or synergistically alleviate gut dysbiosis, inflammation, and cognitive impairment with immune imbalance by controlling IIE and TIE ratios.

9.
Drug Deliv ; 28(1): 2268-2277, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34668836

RESUMO

Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 ± 3.2 nm in diameter and a zeta potential of -18.7 ± 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 °C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear.

10.
Sci Rep ; 11(1): 20406, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650107

RESUMO

Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D+) or without depression (IBD/D-), we analyzed the fecal microbiota composition of patients with IBD with (/D+) or without depression (/D-) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D+ or IBD/D- caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1ß and IL-6 expression, and NF-κB+/CD11c+ cell population in the colon. Transplantation of the IBD/D+ patient feces (IBD/D+-F) caused IBD-like colitis more strongly than that of IBD/D--F. FMTs from patients with IBD/D+ also caused anxiety-/depression-like behaviors, increased the NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell populations, and decreased the BDNF+/NeuN+ cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D- caused anxiety-like, but not depression-like, behaviors. α-/ß-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D+-F vs. IBD/D--F. However, the transplantation of HV-F into mice previously transplanted with IBD/D+-F significantly reduced depression-like behaviors, NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1ß expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.

11.
APL Bioeng ; 5(4): 041505, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34703969

RESUMO

The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development. Conventional in vitro models have limitations in the ability to predict drug effects, due to the lack of physiological relevance. Recently, the liver-on-a-chip platform has been developed to reproduce the microarchitecture and in vivo environment of the liver. These efforts have improved the physiological relevance of the liver tissue used in the platform and have demonstrated its applicability to drug screening and disease models. In this review, we summarize the recent development of liver-on-a-chip models that closely mimic the in vivo liver environments and liver diseases.

12.
Opt Express ; 29(19): 30625-30636, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34614783

RESUMO

In this work, we explore the use of machine learning for constructing the leakage radiation characteristics of the bright-field images of nanoislands from surface plasmon polariton based on the plasmonic random nanosubstrate. The leakage radiation refers to a leaky wave of surface plasmon polariton (SPP) modes through a dielectric substrate which has drawn interest due to its possibility of direct visualization and analysis of SPP propagation. A fast-learning two-layer neural network has been deployed to learn and predict the relationship between the leakage radiation characteristics and the bright-field images of nanoislands utilizing a limited number of training samples. The proposed learning framework is expected to significantly simplify the process of leaky radiation image construction without the need of sophisticated equipment. Moreover, a wide range of application extensions can be anticipated for the proposed image-to-image prediction.

13.
Opt Express ; 29(17): 26955-26970, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615119

RESUMO

In this report, we explore a segmentation-based approach for the calculation of surface plasmon resonance (SPR) on the curved surface with high curvature by modeling it as a contiguous array of finite segments. The approach would significantly facilitate the calculation with good accuracy because of the inherent nature that transfer matrix analysis can be used. Using the segmentation model, resonance characteristics at SPR were obtained as the curvature radius was varied. For validation of the segmentation, resonance wavelength (λSPR), reflectance at resonance (RSPR), and resonance width (δλSPR) were compared with the finite element method in the parallel and perpendicular light incidence. It was found that the results from the segmentation were in excellent agreement, λSPR in particular, while RSPR and δλSPR under parallel incidence showed disparity between the two models due to the short segmentation. Resonance of curved surface on the rigid and flexible substrate was compared and the overall trend was found to be almost identical. The segmentation is expected to provide a simple, fast, and efficient way for studying plasmonic devices with high curvature in flexible and wearable applications.

14.
J Vasc Interv Radiol ; 32(11): 1569-1574.e11, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34717835

RESUMO

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (90Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1-63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 µSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. 90Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a "how-to" for the setup of a preclinical 90Y laboratory are included to support future translational research.

15.
J Med Food ; 24(11): 1169-1171, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34704834

RESUMO

The immunomodulatory effects of Lactobacillus rhamnosus HDB1258 were evaluated in mice with colitis induced by Klebsiella oxytoca (KO). L. rhamnosus HDB1258 was cultured in the lava seawater (LS) to improve its probiotic properties. It increased adhesive ability to mucin with mRNA expression levels of chaperone proteins (such as GroEL/ES, DnaKJ, and HtrA). In the in vivo experiments, administration of KO caused an inflammation on the colon with gut dysbiosis. LH group (oral gavage of HDB1258 1.0 × 109 colony forming units/day) showed that inflammatory biomarkers, including IL-1ß, TNF-α, IL-6, and PGE2, were significantly decreased to less than half of the KO group, and Th1 cells were decreased in the spleen, but Treg cells were not affected. In contrast, the expression levels of secretory IgA and IL-10 were significantly increased, and the composition of gut microbiota in the LH group tended to recover similar to normal mice without any effect on the α-diversity. In conclusion, L. rhamnosus HDB1258 cultured in the LS could regulate competitively pathogenic bacteria in imbalanced flora with its improved mucin adhesive ability and was an effective immunomodulatory adjuvant for treating colitis by its regulatory function on intestinal inflammation.


Assuntos
Colite , Microbioma Gastrointestinal , Lactobacillus rhamnosus , Probióticos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Citocinas , Camundongos , Água do Mar
16.
Eur J Radiol ; 144: 109990, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34638082

RESUMO

PURPOSE: To investigate the feasibility of using 3-dimensional MRF for bone marrow evaluation in the field of view of prostate MRI for T1 and T2 quantification of prostate cancer bone metastases, as well as comparing it to the ADC value. METHODS: In this retrospective study, 30 prostate MRIs were included: 14 cases with prostate cancer bone metastasis and 16 cases without prostate cancer (control). MRF was obtained twice before (nonenhanced [NE] MRF) and after contrast injection (contrast-enhanced [CE] MRF), and T1 and T2 maps were generated from each MRF. Two radiologists independently drew regions of interest (ROIs) on the MRF maps and the ADC maps. Mann-Whitney U tests and the area under the receiver operating characteristic curve (AUROC) evaluated the two-reader means of T1, T2 and ADC values between bone metastasis and normal bone. RESULTS: There were 83 ROIs, including 39 bone metastases and 44 normal bone. The two-reader average ADC, NE T2 and CE T2 values were significantly lower and NE T1 and CE T1 values were significantly higher in metastatic bone compared with normal bone (P < 0.001). The AUROC of the ADC was lowest (0.685), which was significantly lower than those of NE T1 (1.0, P = 0.001), NE T2 (0.932, P = 0.004), and CE T2 (0.876, P = 0.031). CONCLUSION: MRF to assess the pelvic bone during a prostate gland evaluation provides a reliable parametric map for skeletal work-up. With higher diagnostic performance than the ADC value, NE MRF is a potential alternative for quantifying bone marrow metastases in prostate cancer patients.


Assuntos
Neoplasias Ósseas , Neoplasias da Próstata , Neoplasias Ósseas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos
17.
J Chem Phys ; 155(14): 144202, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34654313

RESUMO

In this article, we report the use of randomly structured light illumination for chemical imaging of molecular distribution based on Raman microscopy with improved image resolution. Random structured basis images generated from temporal and spectral characteristics of the measured Raman signatures were superposed to perform structured illumination microscopy (SIM) with the blind-SIM algorithm. For experimental validation, Raman signatures corresponding to Rhodamine 6G (R6G) in the waveband of 730-760 nm and Raman shift in the range of 1096-1634 cm-1 were extracted and reconstructed to build images of R6G. The results confirm improved image resolution using the concept and hints at super-resolution by almost twice better than the diffraction-limit.

18.
Food Funct ; 12(21): 10750-10763, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34608923

RESUMO

Bacterial lipopolysaccharide (LPS) is a risk factor for the outbreak of Alzheimer's disease. Therefore, we isolated Lactobacillus plantarum NK151 and Bifidobacterium longum NK173 from a human fecal bacteria collection, which inhibited Escherichia coli LPS production, and examined their effects on the Escherichia coli K1- or LPS-induced cognitive impairment in mice. Oral gavage of NK151, NK173, or their (4 : 1) mixture (NKm) significantly alleviated Escherichia coli K1-induced cognitive impairment-like behaviors in the Y-maze and novel object recognition tasks. Their treatments decreased IL-1ß, IL-6, and TNF-α expression and NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, while the brain-derived neurotrophic factor (BDNF)+/neuronal nuclei (NeuN)+ cell population and BDNF to proBNDF expression increased. They suppressed LPS-induced cognition impairment-like behaviors and neuroinflammation marker levels in the hippocampus. Treatment with them reduced Escherichia coli K1- or LPS-induced LPS and apolipoprotein E levels in the blood and inflammatory marker levels in the colon. Furthermore, treatment with them modulated fecal Proteobacteria, Bacteroidetes, and Verrucomicrobia populations. Of these gut bacteria, Bacteroidaceae, Odoribacteraceae, Lactobacillaceae, Bifidobacteriaceae, Rikenellaceae, Helicobacteraceae, and Deferribacteraceae are correlated with cognitive function and blood and fecal LPS levels. These findings suggest that NK151 and NK173 may alleviate cognitive impairment with colitis by upregulating NF-κB-mediated BDNF expression through the suppression of fecal and blood bacterial LPS levels.

19.
Micromachines (Basel) ; 12(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34683201

RESUMO

Capacitive deionization (CDI) technology is currently considered a potential candidate for brackish water desalination. In this study, we designed iron oxide nanoparticle-incorporated activated carbon (AC/Fe2O3) via a facile and cost-effective hydrothermal process. The as-synthesized material was characterized using several techniques and tested as electrodes in CDI applications. We found that the distinctive properties of the AC/Fe2O3 electrode, i.e., high wettability, high surface area, unique structural morphology, and high conductivity, resulted in promising CDI performance. The electrosorptive capacity of the AC/Fe2O3 nanocomposite reached 6.76 mg g-1 in the CDI process, with a high specific capacitance of 1157.5 F g-1 at 10 mV s-1 in a 1 M NaCl electrolyte. This study confirms the potential use of AC/Fe2O3 nanocomposites as viable electrode materials in CDI and other electrochemical applications.

20.
Food Funct ; 12(21): 10690-10699, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605514

RESUMO

Memory decline occurs due to various factors, including stress, depression, and aging, and lowers the quality of life. Several nutritional supplements and probiotics have been used to enhance memory function, and efforts have been made to develop mixed supplements with maximized efficacy. In this study, we aimed to examine whether a novel formulation composed of Cuscuta seeds and Lactobacillus paracasei NK112, CCL01, enhances memory function and induces neurogenesis via nerve growth factor (NGF) induction. Firstly, we orally administered CCL01 to normal mice and assessed their memory function 4 weeks after the first administration by performing a step-through passive avoidance test. We found that CCL01 at 100 mg kg-1 treatment enhanced the fear-based memory function. By analyzing the expression of Ki-67 and doublecortin, which are the markers of proliferating cells and immature neurons, respectively, we observed that CCL01 induced neuronal proliferation and differentiation in the hippocampus of the mice. Additionally, we found that the expression of synaptic markers increased in the hippocampus of CCL01-treated mice. We measured the NGF expression in the supernatant of C6 cells after CCL01 treatment and found that CCL01 increased NGF release. Furthermore, treatment of CCL01-conditioned glial media on N2a cells increased neuronal differentiation via the TrkA/ERK/CREB signaling pathway and neurotrophic factor expression. Moreover, when CCL01 was administered and scopolamine was injected, CCL01 ameliorated memory decline. These results suggest that CCL01 is an effective enhancer of memory function and can be applied to various age groups requiring memory improvement.

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