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B-cell maturation antigen (BCMA) has emerged as a promising tumor marker for the diagnosis and treatment of multiple myeloma. The noninvasive and rapid detection of BCMA expression in vivo provides significant value in screening and evaluating multiple myeloma patients receiving BCMA-targeted therapy. We identified the BCMA-targeting peptide BP1 from a one-bead-one-compound (OBOC) peptide library using a high-throughput microarray strategy. The BCMA-targeting specificity and affinity of BP1 were assessed by surface plasmon resonance imaging (SPRi), flow cytometry, and confocal imaging. BCMA-positive (H929) and BCMA-negative (K562) subcutaneous tumor models were established and labeled with 68Ga for BP1, followed by PET imaging and biodistribution studies. PET imaging demonstrated that 68Ga-labeled BP1 has significant specific uptake in multiple myeloma, enabling rapid identification of BCMA expression and precise delineation of the disease. Thus, BP1 represents an ideal candidate for multiple myeloma imaging.
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Increasing studies focus on depolymerization of chondroitin sulfate (CS) to enhance its biological activities. In the present study, low-molecular-weight chondroitin sulfate (LMWCS)iron complexes were obtained by photocatalysis-Fenton reaction. After degradation with the optimal condition of 0.25 % (w/v) TiO2, 10 mM FeSO4, and 400 mM H2O2 for 0, 15, and 60 min, the average relative molecular weights of CS were reduced to 4.77, 2.47, and 1.21 kDa, respectively. Electron paramagnetic resonance and free radical capture test identified â¢OH, â¢O2-, and h+ in the photocatalysis-Fenton system, among them h+ was the major contributor for CS degradation. The structures of degradation products were analyzed by UV, CD, XRD, SEM-EDS, and NMR, and the results indicated that CS chelated iron with its carboxyl and sulfate groups, leading to changes in conformation and microtopography. Then 10 oligosaccharides were identified in the degradation products using HPLC-MSn and the depolymerization mechanism was proposed. Furthermore, iron release was observed in simulated gastrointestinal digestion of LMWCSiron complexes. Notably, the everted gut sac experiment demonstrated that LMWCSiron complex possessed 3.75 times higher iron absorption than FeSO4 (p < 0.01) and 12.60 times higher CS absorption than original CS (p < 0.0001). In addition, LMWCSiron exhibited stronger in vitro antioxidant activity than CS.
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Sulfatos de Condroitina , Peróxido de Hidrógeno , Hierro , Peso Molecular , Titanio , Sulfatos de Condroitina/química , Peróxido de Hidrógeno/química , Hierro/química , Catálisis , Titanio/química , Disponibilidad Biológica , Animales , Procesos FotoquímicosRESUMEN
Due to wonderful taste, rich nutrition and biological functions, many marine green algae in the genus Caulerpa have been recently developed as candidates for green caviar. A novel water-soluble sulfated xylogalactomannan CO-0-1 was obtained from the green algae Caulerpa okamurae. CO-0-1 was mainly composed of mannose (Man), galactose (Gal), and xylose (Xyl) at the ratio of 4.4:4.0:1.4 with the molecular weight at 470 kDa and the sulfate content at 12.78 %. The sulfated xylogalactomannan had Man at the backbone with â4)-ß-D-Manp-(1â and â2)-ß-D-Manp-(1â as the main chain and branches at O-3 position. The side chains contained â3)-ß-D-Galp-(1â and minor â2)-ß-D-Xylp(1â. The sulfate groups only distributed at the side chains and at O-6 position of â3)-ß-D-Galp-(1â and O-4 position of (1â2)-ß-D-Xylp. The anticoagulant activity indicated that CO-0-1 displayed intrinsic anticoagulant and specific anti-thrombin activities. The investigation expanded the utilization and development scene and scope of the green algae Caulerpa okamurae.
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Anticoagulantes , Caulerpa , Mananos , Anticoagulantes/química , Anticoagulantes/farmacología , Anticoagulantes/aislamiento & purificación , Caulerpa/química , Mananos/química , Mananos/farmacología , Mananos/aislamiento & purificación , Peso Molecular , Sulfatos/química , HumanosRESUMEN
Green tea polyphenols (GTP) have been shown to ameliorate lipid metabolic disorders by regulating intestinal bacteria. Given the significant role of intestinal bacteriophages in shaping the gut microbiota, this study investigates GTP's influence on gut bacteriophage-bacteria interactions and lipid metabolism using metagenomics and metabonomics. The research results indicated that GTP significantly reduced body weight, serum triglycerides, leptin, insulin resistance, interleukin-6, and TNF-α levels while increasing adiponectin in ob/ob mice fed high-fat diet, aiding intestinal repair. GTP improved gut health by decreasing Enterobacter, Siphoviridae and Enterobacteria_phage_sfv, increasing Bifidobacterium and intestinal metabolites SCFA and hippuric acid. Correlation analysis showed negative correlations between Enterobacter sp. 50,588,862 and Enterobacteria_phages, Shigella_phages with 4-hydroxyphenylpyruvate and hippuric acid. Bifidobacterium choerinum and Bifidobacterium sp. AGR2158 were positively correlated with fatty acids and bile acids. In conclusion, GTP reduced fat accumulation and inflammation, enhanced gut barrier function in obese mice, closely associated with changes in the gut bacteriophage community.
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Bacterias , Bacteriófagos , Microbioma Gastrointestinal , Metabolismo de los Lípidos , Polifenoles , Té , Animales , Ratones , Polifenoles/farmacología , Polifenoles/administración & dosificación , Polifenoles/metabolismo , Polifenoles/química , Microbioma Gastrointestinal/efectos de los fármacos , Bacteriófagos/metabolismo , Té/química , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Masculino , Metabolismo de los Lípidos/efectos de los fármacos , Humanos , Ratones Obesos , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/fisiopatología , Obesidad/terapia , Obesidad/microbiología , Ratones Endogámicos C57BL , Intestinos/microbiología , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Dieta Alta en Grasa/efectos adversosRESUMEN
Biofilms produced by Candida albicans present a challenge in treatment with antifungal drug. Enhancing the sensitivity to fluconazole (FLC) is a reasonable method for treating FLC-resistant species. Moreover, several lines of evidence have demonstrated that berberine (BBR) can have antimicrobial effects. The aim of this study was to clarify the underlying mechanism of these effects. We conducted a comparative study of the inhibition of FLC-resistant strain growth by FLC treatment alone, BBR treatment alone, and the synergistic effect of combined FLC and BBR treatment. Twenty-four isolated strains showed distinct biofilm formation capabilities. The antifungal effect of combined FLC and BBR treatment in terms of the growth and biofilm formation of Candida albicans species was determined via checkerboard, time-kill, and fluorescence microscopy assays. The synergistic effect of BBR and FLC downregulated the expression of the efflux pump genes CDR1 and MDR, the hyphal gene HWP1, and the adhesion gene ALS3; however, the gene expression of the transcriptional repressor TUP1 was upregulated following treatment with this drug combination. Furthermore, the addition of BBR led to a marked reduction in cell surface hydrophobicity. To identify resistance-related genes and virulence factors through genome-wide sequencing analysis, we investigated the inhibition of related resistance gene expression by the combination of BBR and FLC, as well as the associated signaling pathways and metabolic pathways. The KEGG metabolic map showed that the metabolic genes in this strain are mainly involved in amino acid and carbon metabolism. The metabolic pathway map showed that several ergosterol (ERG) genes were involved in the synthesis of cell membrane sterols, which may be related to drug resistance. In this study, BBR + FLC combination treatment upregulated the expression of the ERG1, ERG3, ERG4, ERG5, ERG24, and ERG25 genes and downregulated the expression of the ERG6 and ERG9 genes compared with fluconazole treatment alone (p < 0.05).
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Antifúngicos , Berberina , Biopelículas , Candida albicans , Biología Computacional , Farmacorresistencia Fúngica , Fluconazol , Pruebas de Sensibilidad Microbiana , Berberina/farmacología , Fluconazol/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/genética , Antifúngicos/farmacología , Farmacorresistencia Fúngica/genética , Biología Computacional/métodos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Sinergismo Farmacológico , Regulación Fúngica de la Expresión Génica/efectos de los fármacosRESUMEN
Recent studies have highlighted the potential of Saccharina japonica Polysaccharides (SJPs) in alleviating high-fat diet (HFD)-induced obesity by regulating gut microbiota, which warrants further exploration to elucidate the underlying structure-activity relationship. In this study, five polysaccharide fractions (Sj-T, Sj-T-1, Sj-T-2, Sj-T-3, and Sj-T-4) with different structure characteristics were prepared from S. japonica, and their effects on HFD-induced obesity and gut microbiota composition were investigated using C57BL/6J mice. The results revealed that oral administration of Sj-T considerably suppressed HFD-induced obesity, glucose metabolic dysfunction, and other disordered symptoms. While, Sj-T-2, which has the lowest molecular weight, was the most effective in alleviating HFD-induced obesity and had the second-best effect on improving HFD-induced impaired glucose tolerance among the five SJPs. Supplementation with SJPs significantly modulated HFD-induced gut microbiota dysbiosis both at the phylum and species levels, such as enriching Desulfobacterota and Actinobacteriota, while suppressing the abundance of Bacteroidota. Sj-T also dramatically restored the gut microbiota composition by modulating the abundance of many crucial gut bacterial taxa, including s_Bacteroides_acidifaciens, s_Lachnospiraceae _bacterium, and g_Lachnospiraceae_NK4A136_group. Besides, SJPs also dramatically altered the function of gut microbiota, including many carbohydrate-metabolism enzymes. This study highlights the potential of SJPs in preventing obesity and restoring intestinal homeostasis in obese individuals.
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Dieta Alta en Grasa , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Obesidad , Polisacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Obesidad/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Ratones , Masculino , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/química , Algas Comestibles , LaminariaRESUMEN
Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their natural products has led to a diminished probability of discovering novel bioactive compounds from this group. Consequently, our research focus has shifted towards less explored actinomycetes, beyond Streptomyces, with particular emphasis on Kitasatospora setae (K. setae). The genome of K. setae was annotated and analyzed through whole-genome sequencing using multiple bio-informatics tools, revealing an 8.6 Mbp genome with a 74.42% G + C content. AntiSMASH analysis identified 40 putative biosynthetic gene clusters (BGCs), approximately half of which were recessive and unknown. Additionally, metabolomic mining utilizing mass spectrometry demonstrated the potential for this rare actinomycete to generate numerous bioactive compounds such as glycosides and macrolides, with bafilomycin being the major compound produced. Collectively, genomics- and metabolomics-based techniques confirmed K. setae's potential as a bioactive secondary metabolite producer that is worthy of further exploration.
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Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.
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Neoplasias Renales , Lutecio , Ratones Endogámicos BALB C , Radioisótopos , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Circonio , Animales , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/farmacocinética , Circonio/química , Ratones , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/metabolismo , Distribución Tisular , Humanos , Línea Celular Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Radiofármacos/farmacocinética , Radiofármacos/química , Nanomedicina Teranóstica/métodos , Femenino , Tomografía de Emisión de Positrones/métodos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Corneal neovascularization (CoNV) threatens vision by disrupting corneal avascularity, however, current treatments, including pharmacotherapy and surgery, are hindered by limitations in efficacy and adverse effects. Minocycline, known for its anti-inflammatory properties, could suppress CoNV but faces challenges in effective delivery due to the cornea's unique structure. Therefore, in this study a novel drug delivery system using minocycline-loaded nano-hydroxyapatite/poly (lactic-co-glycolic acid) (nHAP/PLGA) nanoparticles was developed to improve treatment outcomes for CoNV. RESULTS: Ultra-small nHAP was synthesized using high gravity technology, then encapsulated in PLGA by a double emulsion method to form nHAP/PLGA microspheres, attenuating the acidic by-products of PLGA degradation. The MINO@PLGA nanocomplex, featuring sustained release and permeation properties, demonstrated an efficient delivery system for minocycline that significantly inhibited the CoNV area in an alkali-burn model without exhibiting apparent cytotoxicity. On day 14, the in vivo microscope examination and ex vivo CD31 staining corroborated the inhibition of neovascularization, with the significantly smaller CoNV area (29.40% ± 6.55%) in the MINO@PLGA Tid group (three times daily) than that of the control group (86.81% ± 15.71%), the MINO group (72.42% ± 30.15%), and the PLGA group (86.87% ± 14.94%) (p < 0.05). Fluorescein sodium staining show MINO@PLGA treatments, administered once daily (Qd) and three times daily (Tid) demonstrated rapid corneal epithelial healing while the Alkali injury group and the DEX group showed longer healing times (p < 0.05). Additionally, compared to the control group, treatments with dexamethasone, MINO, and MINO@PLGA were associated with an increased expression of TGF-ß as evidenced by immunofluorescence, while the levels of pro-inflammatory cytokines IL-1ß and TNF-α demonstrated a significant decrease following alkali burn. Safety evaluations, including assessments of renal and hepatic biomarkers, along with H&E staining of major organs, revealed no significant cytotoxicity of the MINO@PLGA nanocomplex in vivo. CONCLUSIONS: The novel MINO@PLGA nanocomplex, comprising minocycline-loaded nHAP/PLGA microspheres, has shown a substantial capacity for preventing CoNV. This study confirms the complex's ability to downregulate inflammatory pathways, significantly reducing CoNV with minimal cytotoxicity and high biosafety in vivo. Given these findings, MINO@PLGA stands as a highly promising candidate for ocular conditions characterized by CoNV.
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Neovascularización de la Córnea , Minociclina , Humanos , Minociclina/farmacología , Neovascularización de la Córnea/tratamiento farmacológico , Neovascularización de la Córnea/prevención & control , Microesferas , Angiogénesis , ÁlcalisRESUMEN
Chemical investigation of Irpex sp. NBUF088, associated with an Ircinia sp. sponge located at an 84 m deep mesophotic zone, led to the discovery of two new heptaketides, named irpetones A (1) and B (2). Their structures were identified by analysis of spectroscopic data and quantum-chemical calculations. Compound 1 exhibited inhibition against the receptor activator of NF-κB ligand-induced osteoclastogenesis in bone marrow monocytes with an IC50 of 6.3 ± 0.2 µM, causing no notable cytotoxicity. It was also determined that 1 inhibited the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and the nuclear translocation of NF-κB, consequently suppressing the activation of MAPK and NF-κB signaling pathways induced by the NF-κB ligand.
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Osteoclastos , Poríferos , Animales , Poríferos/microbiología , Estructura Molecular , Osteoclastos/efectos de los fármacos , FN-kappa B/metabolismo , Ratones , Osteogénesis/efectos de los fármacosRESUMEN
Site-specific covalent conjugation offers a powerful tool to identify and understand protein-protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coli acyl carrier protein (AcpP) with its partner BioF, a key pyridoxal 5'-phosphate (PLP)-dependent enzyme in the early steps of biotin biosynthesis by targeting a tyrosine residue proximal to the active site. We identify the site of crosslink by MS/MS analysis of the peptide originating from both partners. We further evaluate the BioF-AcpP interface through protein crystallography and mutational studies. Among the AcpP-interacting BioF surface residues, three critical arginine residues appear to be involved in AcpP recognition so that pimeloyl-AcpP can serve as the acyl donor for PLP-mediated catalysis. These findings validate an evolutionary gain-of-function for BioF, allowing the organism to build biotin directly from fatty acid biosynthesis through surface modifications selective for salt bridge formation with acidic AcpP residues.
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Biotina , Fluoruros , Compuestos de Azufre , Espectrometría de Masas en Tándem , Biotina/metabolismo , Escherichia coli/metabolismo , Ácidos Grasos/metabolismoRESUMEN
One novel rearranged pimarane diterpenoid, pestanoid A (1), and two reported molecules, nodulisporenones A (2) and B (3), were discovered from Pestalotiopsis sp. NBUF145 fungus associated with a 62 m deep mesophotic ("twilight") zone Chalinidae sponge. The structures of 1-3 were identified by spectrometry, spectroscopy, quantum-chemical calculations, and X-ray crystallography. Compounds 1 and 2 inhibited bone marrow monocyte osteoclastogenesis in vitro with the IC50 values 4.2 ± 0.2 µM and 3.0 ± 0.4 µM, respectively, without observed cytotoxicity. Both 1 and 2 suppressed the receptor activator of NF-kB ligand-induced MAPK and NF-κB signaling by inhibiting the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and NF-κB nuclear translocation.
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Osteoclastos , Osteogénesis , FN-kappa B , Pestalotiopsis , Macrófagos , Abietanos , Ligando RANKRESUMEN
Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000-1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (µCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.
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Enfermedades Óseas , Elementos de la Serie de los Lantanoides , Osteoartritis , Humanos , Microtomografía por Rayos X , Enfermedades Óseas/diagnóstico por imagen , Huesos/diagnóstico por imagen , Osteoartritis/diagnóstico por imagen , Imagen Óptica/métodosRESUMEN
Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20-O-trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20-O-trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure-activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20-O-trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20-O-trimethylsilybins led to the conclusion that (10R,11R) derivatives (silybin A series) are more potent than (10S,11S) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation.
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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising from gastrointestinal tract and can be benign or malignant. Rectal GISTs are rare and have poor prognosis. We here reported an older male who presented with features of distending discomfort in the rectum and pain in the anus due to a large rectal tumor. Physical examinations detected a mass in the rectum without blood staining on the gloved finger. Carcinoembryonic antigen (CEA) was found to be slightly elevated and the prostate-specific antigen level was normal. 18F-FDG PET/CT showed a soft tissue density mass at the bottom of the pelvic, with an unclear boundary to the surroundings with the significantly increased FDG uptake (SUVmax 17.5). Although a rectal carcinoma was suspected based on the finding of PET/CT and CEA, the histopathological examination confirmed the diagnosis of the malignant GIST of the rectum. The patient was then treated with imatinib and on follow-up regularly. In this case, 18F-FDG PET/CT shows the advantage of visualizing both primary and metastatic lesions and provides valuable information for the diagnosis, staging, evaluation, and prognosis of GIST.
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The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Nanopartículas , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , MicroesferasRESUMEN
Lung adenocarcinoma is the most common histologic type of lung cancer. The pixel-level labeling of histologic patterns of lung adenocarcinoma can assist pathologists in determining tumor grading with more details than normal classification. We manually annotated a dataset containing a total of 1000 patches (200 patches for each pattern) of 512 × 512 pixels and 420 patches (contains test sets) of 1024 × 1024 pixels according to the morphological features of the five histologic patterns of lung adenocarcinoma (lepidic, acinar, papillary, micropapillary, and solid). To generate an even large amount of data patches, we developed a data stitching strategy as a data augmentation for classification in model training. Stitched patches improve the Dice similarity coefficient (DSC) scores by 24.06% on the whole-slide image (WSI) with the solid pattern. We propose a WSI analysis framework for lung adenocarcinoma pathology, intelligently labeling lung adenocarcinoma histologic patterns at the pixel level. Our framework contains five branches of deep neural networks for segmenting each histologic pattern. We test our framework with 200 unclassified patches. The DSC scores of our results outpace comparing networks (U-Net, LinkNet, and FPN) by up to 10.78%. We also perform results on four WSIs with an overall accuracy of 99.6%, demonstrating that our network framework exhibits better accuracy and robustness in most cases.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patología , Clasificación del Tumor , Redes Neurales de la ComputaciónRESUMEN
Antisense imaging uses radionuclide labeled antisense oligonucleotides to hybridize with nucleic acids in vivo, display the expression of target genes, and directly quantify biological processes at the cellular and subcellular levels. The anti-miRNA oligonucleotides (AMOs) are a series of single-stranded DNA oligonucleotides that are widely used in gene imaging and gene therapy. However, due to the negative charge and high molecular weight, the permeability through the membrane of AMOs is generally low so that most AMOs cannot enter the cells. Based on the 99mTc-labeled AMOs imaging in previous studies, this study developed a novel tetrapeptide Glycine-Alanine-Glycine-Lysine (Gly-Ala-Gly-Lys, GAGK) for one-step labeling AMO with 99mTc. The labeling conditions were optimized by changing the number of stannous ions, the reaction time, and the temperature, respectively. The labeled products were identified by gel electrophoresis and their serum stability was evaluated. The optimal labeling condition in this study was using 1 mg/mL SnCl2·2H2O and heating for 30 min at 100°C. Gel electrophoresis confirmed the verification of successful labeling of 99mTc-GAGK-AMO. After being incubated with human fresh serum for 12 h, 99mTc-GAGK-AMO showed good stability and no obvious degradation. Therefore, this labeling method has high labeling efficiency and stable labeling, which provides an effective method for the application of miRNA-targeted imaging.
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Five undescribed phenylpropanoids, one undescribed phenolic glucoside, and sixteen known compounds were isolated from Brachybotrys paridiformis Maxim. Ex Oliv. The undescribed compounds were named brachoside B-C, brach acid A-B, brachnan A, and brachin D, respectively. Additionally, the anti-hepatitis B virus activities of all isolated compounds were studied. Among them, brachnan A, brach acid A, globoidnan A, 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxy-phenyl)-naphthalene, and 3,4-dihydroxybenzaldehyde showed significant anti-hepatitis B virus activities.
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Boraginaceae , Glucósidos , Virus de la Hepatitis B , Naftalenos , Extractos VegetalesRESUMEN
Roughly 268,000 new cases of prostate cancer and 34,000 deaths from prostate cancer are projected by the American Cancer Society to occur in the United States in 2022. Androgen receptor is a key protein in the proliferation and survival of prostate cancer cells and has been revealed to be overexpressed in 30% to 50% of castration-resistant prostate cancer patients. One promising approach to reducing the level of this protein is Proteolysis Targeting Chimeras (PROTACs) that is an emerging drug discovery technology. PROTACs are hetero-bifunctional molecules where one end binds to a protein of interest and the other to an E3 ligase ligand, initiating the Ubiquitin-Proteasome Pathway for protein degradation. Two PROTACs with niclosamide as androgen receptor ligand and VHL-032 as the E3 ligase ligand have been designed and synthesized for suppressing proliferation of androgen receptor-positive prostate cancer cells via degrading androgen receptor. The in vitro antiproliferative assessment suggested that they can selectively suppress PC-3, LNCaP, and 22Rv1 prostate cancer cell proliferation, but cannot inhibit DU145 cell proliferation. However, the mechanism of both compounds in suppressing prostate cancer cell proliferation is not through the AR PROTAC mechanism because they did not degrade AR in our Western Blotting assay up to 1 µM.