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BACKGROUND: To discuss the first case of mitomycin C (MMC) toxicity after XEN® gel stent implantation in a glaucoma patient, conducted using the XEN "air" technique with an ophthalmic viscosurgical device (OVD). CASE PRESENTATION: A 44-year-old Asian male presented with increased intraocular pressure (IOP; 52 mmHg) accompanied by keratic precipitates and an edematous cornea. He was diagnosed with uveitic glaucoma in the left eye, and the IOP was controlled with a topical anti-glaucoma agent. However, glaucoma progression was revealed by Humphrey visual field (HVF) and optical coherence tomography (OCT) examinations. The patient underwent uneventful XEN gel stent implantation using the XEN air technique and an MMC (0.02%, 0.1 mL) injection, with subconjunctival air and OVD injection provided prior to XEN implantation in the left eye. The patient exhibited a decreased IOP (11 mmHg), elevated bleb, and extensive subconjunctival hemorrhage on postoperative day 1. On postoperative day 18, diffuse conjunctival injection and a large avascular bleb was noticed around the XEN gel stent. The patient complained of severe eye pain and discomfort, suggestive of MMC toxicity, and the IOP was 12 mmHg. The patient was treated with a topical steroid and antibiotics tapered over a 6-month period. Finally, the toxicity was successfully controlled, with the IOP stabilizing at around 15 mmHg. CONCLUSIONS: Although significantly greater lowering of the IOP can be expected with the use of subconjunctival OVD injection and MMC during XEN gel stent implantation, a cautious approach and a longer monitoring period are required.
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Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Masculino , Adulto , Mitomicina/efeitos adversos , Pressão Intraocular , Glaucoma de Ângulo Aberto/cirurgia , Implantes para Drenagem de Glaucoma/efeitos adversos , Resultado do Tratamento , Glaucoma/cirurgia , Stents/efeitos adversosRESUMO
Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.
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Exossomos , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Degeneração Retiniana , Cirurgiões , Ratos , Humanos , Animais , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/metabolismo , Proteínas Quinases Ativadas por Mitógeno , Exossomos/metabolismo , Espécies Reativas de Oxigênio , Células-Tronco Pluripotentes Induzidas/metabolismoRESUMO
Animal placentae can be used as health-promoting food ingredients with various therapeutic efficacies, but their use is limited by their unpleasant odor and taste. This study aimed to investigate the possibility of deodorization of sheep placenta via yeast fermentation. A yeast strain was successfully isolated and identified as a novel Brettanomyces strain (Brettanomyces deamine kh3). The deodorizing efficacy of fermentation of the sheep placenta with B. deamine kh3 was evaluated by 42 panels, based on evaluation of preference, ranking, and aroma profiles, and compared with normal placenta and placenta fermented with B. bruxellensis. The results of the sensory evaluation indicated that fermentation of the sheep placenta with B. deamine kh3 may improve its palatability by increasing flavors such as that of grass (tree), rubber, and burnt, and by decreasing the odor and soy sauce flavor. Solid-phase microextraction-gas chromatography (SPME-GC) showed that major off-flavors in sheep placenta, such as ammonia, dimethyl disulfide, and 1,3-dioxolane, were completely diminished in the sheep placenta fermented with B. deamine kh3. This study presents those major volatile compounds, including 2-isobutyl\-4,4-dimethyl-1,3-dioxane, and 3-methyl-1-butanol, could be crucial in improving the palatability of the sheep placentae fermented with B. deamine kh3. This study provides a good starting point for the industrial application of a new deodorization method.
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Brettanomyces/fisiologia , Fermentação , Aromatizantes/isolamento & purificação , Malus/química , Odorantes/análise , Placenta/metabolismo , Animais , Brettanomyces/isolamento & purificação , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Placenta/química , Gravidez , Ovinos , Microextração em Fase Sólida , Compostos Orgânicos VoláteisRESUMO
The aim of the present study was to report two cases of refractory dry eye syndrome (DES) after transconjunctival excision of the palpebral lobe of the lacrimal gland. A 25-year-old female patient with a chief complaint of a palpable mass in both upper eyelids visited our medical center. Preoperative orbital computer tomography showed high-attenuation lesions in both lacrimal glands. Incisional biopsy of the lacrimal gland palpebral lobe via transconjunctival incision was performed in January 2019. At 1 month after the biopsy, a lack of tears and persistent corneal erosions were found in both eyes. Artificial tears, punctal occlusion, autologous serum eye drops, and therapeutic contact lenses were applied in an attempt to control the dry eye symptoms. The patient continues to suffer from intractable DES at 2.5 years after the procedure. The second case involved a 52-year-old female patient who visited our medical center with a chief complaint of a palpable mass in both upper eyelids. Bilateral orbital tumors were diagnosed with preoperative magnetic resonance imaging. An incisional biopsy of the lacrimal gland was performed. Immunoglobulin G4-related dacryoadenitis was confirmed through lacrimal palpebral lobe incisional biopsy. Intractable DES and corneal erosion of her left eye persisted thereafter. A transconjunctival incision is an effective approach for minimizing postoperative scars and is suitable for the biopsy of tumors that are visible through the conjunctiva. After a biopsy of the palpebral lobe of the main lacrimal glands, the secretion of reflex tears decreases due to damage to the secreting ducts of the main lacrimal glands. However, total tear secretion can be maintained by basal tear secretion from the accessory lacrimal glands. In this report, we describe two cases of refractory DES due to decreased total tear secretion, although only the palpebral lobes of the main lacrimal glands were biopsied.
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Síndromes do Olho Seco , Aparelho Lacrimal , Adulto , Túnica Conjuntiva/cirurgia , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/cirurgia , Pálpebras , Feminino , Humanos , Aparelho Lacrimal/diagnóstico por imagem , Aparelho Lacrimal/cirurgia , Pessoa de Meia-Idade , LágrimasRESUMO
The demands for a power-saving mode for displaying static images are ubiquitous not only in portable devices but also in price tags and advertising panels. At a low-frequency driving in liquid crystal displays (LCDs) for low-power consumption, the flexoelectric effect arises even in calamitic liquid crystals and the optical appearance of this physical phenomenon is found to be unusually large, being noticed as an image-flickering. Although the inherent integrated optical transmittance of in-plane switching (IPS) mode is relatively lower than that of fringe-field switching (FFS) mode, the IPS mode shows no static image-flickering but an optical spike (the so-called optical bounce), at the transient moment between signal positive and negative frames. Here, we demonstrate an IPS mode using negative dielectric anisotropy of liquid crystals (Δε < 0) and fine-patterned electrodes (the width w of and the space l between electrodes ≤ 3 µm) with reduced operation voltage (up to 40.7% to a conventional FFS mode with Δε < 0), reduced optical bounce (up to 4.4%. to a conventional FFS mode with Δε < 0) and enhanced transmittance (up to 32.1% to a conventional IPS mode with Δε > 0). We believe the result will contribute not only to the scientific understanding of the optical appearance of flexoelectric effect but also pave the way for engineering of a superior low-power consumption LCD.
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Sarcopenia is considered to be a risk factor for osteoporotic fracture, which is a major health problem in elderly women. In this study, we aimed to investigate the association of sarcopenia, with regard to muscle mass and function, with prevalent vertebral fracture in community-dwelling elderly women. We recruited 1281 women aged 64 to 87 years from the Korean Urban Rural Elderly cohort study. Muscle mass and function were measured using bioimpedance analysis and jumping mechanography. Skeletal muscle index (SMI) and jump power were used as an indicator of muscle mass and function, respectively. Among the participants, we observed 282 (18.9%) vertebral fractures and 564 (44.0%) osteoporosis. Although age, body mass index, and prevalence of osteoporosis increased as both SMI and jump power decreased, prevalence of vertebral fracture increased only when jump power decreased. In univariate analysis, compared with the highest quartile of jump power, the lowest quartile had a significant odds ratio of 2.80 (95% CI 1.79-4.36) for vertebral fracture. This association between jump power and vertebral fracture remained significant, with an odds ratio of 3.04 (95% CI 1.77-5.23), even after adjusting for other risk factors including age, bone mineral density, previous fracture, and cognitive function. In contrast, there was no association between SMI and vertebral fracture. Based on our results, low jump power, but not SMI, is associated with vertebral fracture in community-dwelling elderly Korean women. This finding suggests that jump power may have a more important role than muscle mass itself for osteoporotic fracture.
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Músculo Esquelético/patologia , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Sarcopenia/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Densidade Óssea/fisiologia , Estudos de Coortes , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Musculares/epidemiologia , Osteoporose/complicações , Prevalência , Sarcopenia/fisiopatologiaRESUMO
The gut microbiota composition in animals and humans has recently been found to be influenced by exercise. Although Limosilactobacillus reuteri strains have notable probiotic properties that promote human health, understanding of its effects in combination with exercise and physical activity is limited. Therefore, this study examined the effects of L. reuteri ID-D01, a human-derived probiotic, on exercise performance and fatigue in Sprague-Dawley rats. Organ weight, maximal running distance, serum biochemistry, muscle performance, microbial community composition, and short-chain fatty acid (SCFA) levels were assessed. Results indicated that ID-D01 supplementation significantly improved endurance performance. Rats in the probiotic group demonstrated a significant increase in maximal running distance compared with that in the control group (p < 0.05). Additionally, levels of fatigue markers, such as lactate and creatine phosphokinase, were significantly reduced in the ID-D01-administered groups, suggesting its potential to alleviate exercise-induced fatigue. Microbiome analysis revealed a distinct shift in gut microbiota composition in response to ID-D01 administration. The group that received ID-D01 probiotics exhibited a significant increase in the abundance of SCFA-producing bacteria, particularly Akkermansia spp., compared with that in the control groups. Furthermore, they showed elevated production of SCFAs, such as acetate and butyrate. In conclusion, this study demonstrated that ID-D01 can enhance exercise performance and reduce fatigue. Herein, we highlighted that human-derived probiotics could improve physical performance, as observed by changes in gut microbiota composition and SCFA production.
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BIOVITA 3 bacterial species (BIOVITA 3), a probiotic blend powder containing Clostridium butyricum IDCC 1301, Weizmannia coagulans IDCC 1201 and Bacillus subtilis IDCC 1101, has been used as a food ingredient for gut health. However, its efficacy in improving constipation has not been reported. Therefore, we aimed to investigate the functional effects of oral administration of BIOVITA 3 as well as its component strains alone (at 1.0×109 CFU/day) in Sprague-Dawley (SD) rats with loperamide-induced constipation. The study included fecal analysis, gastrointestinal transit ratio, histopathological analysis, short chain fatty acids (SCFAs), and metagenome analysis. As results, the BIOVITA 3 group showed significant improvements in fecal number, water content, gastrointestinal transit ratio, and thickening of the mucosal layer. In the SCFAs analysis, all probiotic-treated groups showed an increase in total SCFAs compared to the loperamide-constipated group. Changes in microbial abundance and the diversity index of three groups (normal, constipated, and BIOVITA 3) were also defined. Of these, the BIOVITA 3 showed a significant improvement in loperamide-constipated SD-rats. This study suggests the possibility that BIOVITA 3 can be applied as an ingredient in functional foods to relieve constipation.
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This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine-which are the intermediates in purine metabolism-for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.
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Hiperuricemia , Nucleosídeos de Purina , Ratos , Animais , Humanos , Nucleosídeos de Purina/metabolismo , Ácido Úrico , Hiperuricemia/metabolismo , Nucleosídeos , Streptococcus thermophilus , Ratos Sprague-Dawley , XantinaRESUMO
The PI3K/AKT/FOXO3 pathway is one of the most frequently involved signaling pathways in cancer, including breast cancer. Therefore, we synthesized a novel lysine-rich polypeptide (Lys-PP) using de novo assembly method and evaluated its anticancer effect. We characterized the structural and physicochemical properties of Lys-PP using various techniques. Later, we used integrated approaches such as in silico, in vitro, and in vivo analysis to confirm the anticancer and therapeutic effect of Lys-PP. First, RNA sequencing suggests Lys-PP disrupted the central carbon metabolic pathway through the modulation of prolactin signaling. Additionally, docking analysis also confirmed the significant association of PI3K/AKT and FOXO3 pathway to induce an apoptotic effect on cancer. Second, Lys-PP exhibited a significant cytotoxicity effect against MDA-MB-231 but no cytotoxic effects on RAW 264.7 and HEK-293, respectively. The cytotoxic effect of Lys-PP-induced apoptosis by an increase in FOXO3a protein expression and a decrease in PI3K/AKT pathway was confirmed by quantitative real-time polymerase chain reaction, immunoblotting, and fluorescent microscopy. Later, immunohistochemistry and hematoxylin and eosin staining on MDA-MD-231 showed increased FOXO3a expression and cell death in the xenograft mice model. Further, liver function, metabolic health, or lipid profile upon Lys-PP showed the absence of significant modulation in the biomarkers except for kidney-related biomarkers. Overall, our comprehensive study provides the first evidence of Lys-PP antibreast cancer action, which could serve as a potential treatment in an alternative or complementary medicine practice.
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BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents. OBJECTIVE: This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment. METHODS: Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n = 10) and DWP SID group (n = 9). In the DWP TOD group, 0.025 mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025 mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups. RESULTS: No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p < 0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n = 5, DWP SID group n = 5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001. CONCLUSION: When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose.
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Benzofuranos , Doenças do Cão , Hipoglicemiantes , Insulina , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Cães , Projetos Piloto , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Doenças do Cão/tratamento farmacológico , Masculino , Feminino , Hipoglicemiantes/administração & dosagem , Quimioterapia Combinada/veterinária , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/veterináriaRESUMO
Administering more than 10 times the therapeutic dose of insulin is extremely rare in diabetic dogs and is life threatening with hypoglycemia and seizures if not accompanied by appropriate treatment. A 15-year-old, castrated male miniature poodle dog managed for diabetes presented with depression, disorientation, ataxia, and cluster seizures. The dog had been administered 11.1 U/kg of neutral protamine hegadorn (NPH) insulin (10 times the prescribed dose) 3 h before the onset of symptoms. Blood analysis revealed hypoglycemia, with a circulating glucose level of <50 mg/dL. To treat the hypoglycemia-induced seizures, dextrose was repeatedly administered intravenously. Repeated generalized seizures were treated with anticonvulsants and intermittent mannitol. Since refractory hypoglycemia persisted 24 h after the insulin overdose, it was decided to proceed with glucagon treatment (15-30 ng/kg/min titrated to the blood glucose level after a loading dose of 50 ng/kg intravenous bolus infusion). After 37 h of glucagon treatment, blood glucose levels stabilized. After entering a hyperglycemic state, NPH insulin was administered to manage insulin-dependent diabetes mellitus. This is the first case documented of successful treatment with glucagon, anticonvulsants and intermittent mannitol for refractory hypoglycemia and seizure caused by fatal insulin overdose. Thus, it has great clinical value in veterinary medicine.
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Graves' orbitopathy (GO) is a complex autoimmune disorder of the orbit that causes the eye to appear disfigured. GO is typically associated with Graves' disease, an inflammatory autoimmune condition that is caused by thyrotropin receptor autoantibodies. Although our knowledge of the pathophysiology of GO has improved, its exact pathogenesis remains unclear. Some patients suffer from disfigurement, double vision, and even vision loss rather than hyperthyroidism. The disease severity and activity prompt different treatments, as the signs of GO are heterogeneous, so their management can be very complex. Despite medical advances, the first-line treatment for moderate-to-severe active GO is still glucocorticoids, while surgery can be critical for the treatment of chronic inactive GO. Surgery is sometimes required in the acute phase of the disease when there is an immediate risk to vision, such as in dysthyroid optic neuropathy. Most surgeries for GO are rehabilitative and subdivided into three categories: decompression, strabismus repair, and lid surgery. This review is a basic overview of the field, with up-to-date knowledge of the surgical techniques for GO. We review and summarize recent literature on the advances in surgery for GO to provide up-to-date insights on the optimal surgical treatment for GO.
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Doença de Graves , Oftalmopatia de Graves , Hipertireoidismo , Doenças do Nervo Óptico , Humanos , Doença de Graves/diagnóstico , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/cirurgia , Hipertireoidismo/complicações , Órbita/patologiaRESUMO
Ginsenoside compound K (CK) has been shown to exhibit anti-inflammatory properties. In this study, to encourage biomedical applications of biosynthesized gold nanoparticles (AuNPs) with anti-inflammatory effects, AuNPs loaded with ginsenoside compound K were prepared using a self-assembly technique with chitosan as the carrier. Optimal conditions for chitosan-ginsenoside CKgold nanoparticles (CS-CK-AuNPs) formation were monitored using UV-Vis absorption spectroscopy. The physicochemical characterization of CS-CK-AuNPs was performed using FE-TEM, FE-SEM, XRD, DLS, FTIR and NMR techniques. In the stability test, CS-CK-AuNPs did not show any significant changes up to 4 weeks. Fluorescence imaging demonstrated that CS-CK-AuNPs promoted cellular uptake in vitro, but did not exhibit significant cytotoxicity at concentrations below 40 µg/mL. Additionally, the CS-CK-AuNPs inhibited NO production, and reduced the expression and secretion of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) via inhibition of the nuclear factor-kappaB (NF-κB) pathway in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Thus, CS-CK-AuNPs are novel candidates for developing anti-inflammatory agent. This study also confirms the superiority of chitosan AuNPs as oral delivery vehicles for inflammation-related diseases.
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Quitosana , Nanopartículas Metálicas , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Quitosana/química , Ginsenosídeos , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/químicaRESUMO
BACKGROUND: In our previous study, Hibiscus syriacus leaf tissue was successfully cultivated in an optimized callus culture system, and subsequently extracted with 70% ethanol to prepare H. syriacus callus extract (HCE). The previous study suggested that the callus culture is useful method for obtaining the anti-inflammatory ingredients from H. syriacus. PURPOSE: In the present study, we aimed to investigate the effect of HCE on the colorectal cancer (CRC) and its underlying mechanism of action using HT-29 cells and thymus-deficient mice bearing HT-29 xenografts. METHODS: The cytotoxicity of HCE was investigated by MTT and colonies formation. The underling mechanism by which HCE regulates specific proteins in HT-29 cells was evaluated by the proteomic analysis. These putative proteins were validated using qRT-PCR and immunoblotting analyses. Subsequently, oral administration of HCE for 15 days further evaluating the anti-tumor activity by mRNA and protein expressions levels and tumor histopathology. RESULTS: Results of cell viability and colony formation assays revealed a significant cytotoxic effect of HCE at doses below 100 µg/ml against HT-29 cells, but not against normal cells. Through differential protein expression analysis, signaling pathways underlying anti-CRC activity were predicted in HCE-treated HT-29 cells: Notch signaling, cholesterol biosynthesis, and AMPK signaling pathways. qRT-PCR and immunoblotting analyses indicated that the cytotoxic effect of HCE against HT-29 cells might be associated with the suppression of Notch signaling, which positively contributes to cholesterol biosynthesis. To our knowledge, this can be presented as the first study to demonstrate the detailed relationship between Notch signaling and cholesterol-AMPK signaling. Our in vivo result further corroborated the in vitro finding that 100 and 200 mg/kg HCE for 15 days exerts its anti-cancer effect via Notch signaling-mediated suppression of cholesterol synthesis without systemic toxicity. CONCLUSION: Our findings can serve as a starting point for developing the novel anti-CRC agent using HCE, as a targeted medicine acting on regulating Notch signaling and cholesterol synthesis.
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Neoplasias Colorretais , Hibiscus , Animais , Neoplasias Colorretais/tratamento farmacológico , Células HT29 , Humanos , Camundongos , Proteômica , Transdução de SinaisRESUMO
BACKGROUND: Silymarin, a blend of flavonolignans isolated from plant Silybum marianum L., has long been used as an herbal medicine. Biogenic routes especially the plant-based synthesis of selenium nanoparticles (SeNPs) is safe, eco-friendly, nontoxic and being considered as one of the best strategies for treatment of cancer. PURPOSE: Silymarin-mediated green synthesis of SeNPs and their possibility as an anticancer agent have not been reported to date. Therefore, our present study was aimed to synthesize and characterize the selenium mediated silymarin nanoparticles (Si-SeNPs) from silymarin and investigate their possibility as an anticancer agent. METHODS: The physicochemical characteristics of Si-SeNPs were analyzed using various analytical techniques, such as HPLC, field emission-transmission electron microscope, energy-dispersive X-ray spectrometer, and thermogravimetric analysis. The underlying molecular mechanism were evaluated using AGS gastric cancer cells. RESULTS: Compared with silymarin, the Si-SeNPs exhibited significantly increased cytotoxic effect of AGS cells without exhibiting toxicity on normal cells. Real time PCR and western blotting analysis indicated that Si-SeNPs induced expression of Bax/Bcl-2, cytochrome c, and cleavage of caspase proteins, which is associated with mitochondria-mediated apoptosis signaling in AGS cells. Moreover, agonist assay using PI3K activator indicated that Si-SeNPs-inhibited PI3K/AKT/mTOR pathways were significantly associated as an autophagy and apoptosis signaling in AGS cells. CONCLUSION: Our study demonstrated the improved anticancer efficacy of Si-SeNPs- induced apoptosis and autophagy pathways, and therefore recommended Si-SeNPs as a novel anticancer agent after in vivo studies.
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BACKGROUND: Despite great advances in the field of immunotherapy, there is still a need for novel and effective immunostimulants to overcome challenges, such as instability and autoinflammatory toxicity, associated with conventional immunostimulants. Nanotechnology provides the possibility to overcome these challenges. The well-known classical Chinese formula, Hwanglyeonhaedok-tang (HHT) has been widely used to treat immune-related diseases in clinical practice. METHODS: We developed novel gold nanoparticles (AuNPs) utilizing one-pot synthesis with the herbal formula-HHT. The optimal conditions for HHT-AuNP biosynthesis were established, and physicochemical properties of the optimized HHT-AuNPs were identified using various spectrometric and microscopic techniques. Bio-TEM analysis revealed that HHT-AuNPs were highly engulfed within RAW264.7 cells without inducing cytotoxicity. The effect of HHT-AuNPs on immunostimulatory activity was evaluated in innate and adaptive immune cells (RAW264.7 macrophages and ICR mice splenocytes) using qRT-PCR, immunoblotting, and ELISA. RESULTS: The HHT-AuNPs remarkably increased the nitric oxide (NO) and immune-related cytokines production by activating the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways in RAW264.7 cells. Furthermore, HHT-AuNPs exerted immunostimulatory effects on mouse splenocytes by priming T/B-cells and macrophages. DISCUSSION: The present study is the first to demonstrate that HHT-AuNPs could be utilized as immunostimulators to activate both innate and adaptive immune systems. These results provide a foundation for the application of traditional Chinese medicinal formulae in the field of nanomedicine.
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Ouro , Nanopartículas Metálicas , Animais , Lipopolissacarídeos , Macrófagos , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B , BaçoRESUMO
Postbiotics defined as soluble factors (products or metabolic byproducts) that are released after bacterial lysis or secreted by live bacteria, have attracted considerable attention because of their long shelf life, safety, and beneficial effects. In this study, we investigated the immune-enhancing activities of squid jeotgal (a traditional Korean fermented seafood)-derived Bacillus velezensis Kh2-2 (Kh2-2) postbiotics in vitro, ex vivo, and in vivo. Cell lysates of four Bacillus species were prepared by sonication. In particular, Kh2-2 lysates induced NO production by upregulating iNOS expression in RAW264.7 cells compared with the lysates of B. subtilis Kh2-1, B. vallismortis Kh8-3, and B. amyloliquefaciens Kh3-1. Furthermore, Kh2-2 lysates stimulated immune activation of macrophages by upregulating the NF-κB and MAPK signaling pathways and promoting immune-related cytokine secretion. In the ex vivo study, Kh2-2 lysates stimulated proliferation and polarized Th1 response by inducing the production of IL-2 and IFN-γ and inhibiting IL-10 expression in splenocytes. The in vivo immune-enhancing effects of Kh2-2 lysates and Kh2-2 were further evaluated using a cyclophosphamide (CTX)-induced immunosuppression mouse model. The results showed that oral administration of Kh2-2 lysates improved CTX-induced immunosuppression by enhancing innate and adaptive immunity, stimulating immune-related cytokine secretion, and modulating gut microbiota dysbiosis in mice. Thus, we concluded that Kh2-2 lysates have potential as a functional material for postbiotics with immune-enhancing effects.
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Bacillus , Animais , Bacillus/metabolismo , Macrófagos , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7RESUMO
BACKGROUND: Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. METHODS: Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and ß-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. RESULTS: GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root's biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. CONCLUSION: These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1.
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Semi-invasive or invasive aspergillosis occurring following chemotherapy with sunitinib is a rare condition with unknown incidence and prognosis. Here, we report a case involving a 59-year-old male who had a history of underlying stable aspergilloma and was newly diagnosed with metastatic renal cell carcinoma. Following surgical resection for renal cell carcinoma and adjuvant chemotherapy with sunitinib for 8 months, the patient presented with hemoptysis. Chest computed tomography revealed an increased soft tissue mass and air crescent sign of the underlying aspergilloma, combined with consolidation and bronchial artery hypertrophy around the lesion. The patient underwent bronchoscopy with a biopsy of the lesion and was eventually diagnosed with chronic necrotizing pulmonary aspergillosis, which had progressed from the underlying stable aspergilloma. This case highlights the fact that clinicians should be aware of the risk of opportunistic conversion from stable aspergilloma to invasive fungal infections in patients undergoing sunitinib treatment.