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Lipid accumulation is a factor contributing to the pathogenesis of acute kidney injury (AKI), yet there are currently no approved pharmacotherapies aside from adjuvant therapy. A developed reactive oxygen species (ROS)-responsive drug delivery system (NPSBG@Cur) was developed to deliver the autophagy activator curcumin (Cur) in order to alleviate AKI by activating autophagy and promoting lipid droplet degradation. The nanoparticles were shown to be ROS-responsive in the H2O2 medium and demonstrate ROS-responsive uptake in palmitate (PA)-induced oxidative stress-damaged cells. NPSBG@Cur was found to effectively inhibit lipid accumulation by autophagosome transport in kidney tubular cells. Additionally, in a mouse AKI model, NPSBG@Cur was observed to significantly ameliorate renal damage by activating autophagy flux and improving lipid transport. These results suggest that the ROS-responsive drug delivery system augmented the therapeutic effect of Cur on AKI by improving lipid metabolism through autophagy activation. Therefore, targeting lipid metabolism with NPSBG@Cur may be a promising AKI treatment strategy.
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Injúria Renal Aguda , Curcumina , Nanopartículas , Camundongos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Injúria Renal Aguda/tratamento farmacológico , LipídeosRESUMO
Sewage sludge incineration ash (SSIA) is rich in phosphorus (P), thus being considered as a reliable source of phosphorus recovery. Different P species behaved significant bioavailability. Based on this, a comprehensive investigation into the bioavailability transition path of P species during sewage sludge (SS) incineration was conducted. P predominantly existed in the form of inorganic phosphorus (IP) in SS with a higher concentration of non-apatite inorganic phosphorus (NAIP) and less concentration of apatite inorganic phosphorus (AP). During the SS incineration process, OP existed in the flocs and cell structures of SS underwent destruction, the released P then combined with metal elements such as Ca, Mg, Fe, and Al to form AP species (Ca/Mg-P) and NAIP species (Fe/Al/Mn-P), and the NAIP decomposition to release into gas phase. This was the initial step for enhancing the bioavailability of P species. As temperature increased and the incineration process progressed, the low-temperature-resistant NAIP dissociated, and the metal-binding sites of Al, Fe and Mn in NAIP species were gradually replaced by the Ca and Mg thus forming thermal stability AP species (Ca/Mg-P, such as CaHPO4, Ca2PO4Cl, and Mg3(PO4)2 et al.). This step was crucial for the bioavailability improvement of P species during the incineration process. Therefore, the IP proportions in TP were extremely high (ï¼98%), and this value gradually increased as incineration temperature raised. The higher incineration temperature, the lower NAIP concentration and higher AP concentration. Besides, additives such as coal/rice husk/eggshell played a significant affect. Additives wither higher Ca content were inclined to react with P to form Ca/Mg-P (AP), while the presence of SO2 would react with Ca metals to form CaSO4 thus inhibiting the formation of AP species (such as CaHPO4 and CaPO4Cl). This results could provide theoretical support for the efficient and directional migration of P during sewage sludge incineration.
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Fósforo , Esgotos , Disponibilidade Biológica , Incineração , Temperatura AltaRESUMO
OBJECTIVES: Chinese herbal medicine (CHM) is widely used in breast cancer, but there is no consensus on the Chinese medicine (CM) syndromes in the different conventional treatment stages (preoperative, postoperative, chemotherapy, radiation therapy and endocrine therapy) of early breast cancer. This Delphi study aimed to achieve expert consensus on the CM syndromes, signs and symptoms, and the Chinese herbal formulae for early breast cancer. METHODS: Thirty senior CM clinicians with expertise in managing breast cancer were enrolled. The syndromes selected by ≥50% of experts and the corresponding most common Chinese herbal formulae were considered a consensus. Consensus on signs and symptoms was defined as a median score ≥4 (the item was important or very important) and ≥70% of experts rating the sign or symptom as 4 (important) or 5 (very important) on a 5-point Likert scale. RESULTS: Three survey rounds were conducted from 15 October 2021 to 10 March 2022. Consensus was reached with 3 syndromes confirmed for each treatment stage. Several syndromes, such as dual deficiency of qi and Blood, were considered common to multiple treatment stages. Some important signs and symptoms were presented in multiple treatment stages (eg, shortage of qi in the radiation therapy and endocrine therapy stages). CONCLUSIONS: This Delphi study achieved consensus on the most common CM syndromes, corresponding signs and symptoms, and the most common formulae in each treatment stage of early breast cancer, providing an evidence-based approach for future clinical practice.
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Neoplasias da Mama , Medicina Tradicional Chinesa , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Consenso , Técnica Delphi , Inquéritos e QuestionáriosRESUMO
Natural products have provided abundant sources of lead compounds for new drug discovery and development over the past centuries. Curcumin is a lipophilic polyphenol isolated from turmeric, a plant used in traditional Asian medicine for centuries. Despite the low oral bioavailability, curcumin exhibits profound medicinal value in various diseases, especially liver and gut diseases, bringing an interest in the paradox of its low bioavailability but high bioactivity. Several latest studies suggest that curcumin's health benefits may rely on its positive gastrointestinal effects rather than its poor bioavailability solely. Microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the intestine and liver, suggesting the possibility that the liver-gut axis bidirectional crosstalk controls gastrointestinal health and diseases. Accordingly, these pieces of evidence have evoked great interest in the curcumin-mediated crosstalk among liver-gut system diseases. The present study discussed the beneficial effects of curcumin against common liver and gut diseases and explored the underlying molecular targets, as well as collected evidence from human clinical studies. Moreover, this study summarized the roles of curcumin in complex metabolic interactions in liver and intestine diseases supporting the application of curcumin in the liver-gut system as a potential therapeutic option, which opens an avenue for clinical use in the future.
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BACKGROUND AND AIMS: Gut microbiota are recognized to be important for anticancer therapy, yet the underlying mechanism is not clear. Here, through the analysis of clinical samples, we identify the mechanism by which the gut microbial metabolite butyrate inhibits HCC and then explore new strategies for HCC treatment. APPROACH AND RESULTS: In our study, we demonstrate that gut microbial metabolite butyrate improves anticancer therapy efficacy by regulating intracellular calcium homeostasis. Using liquid chromatography-mass spectrometry analysis, we found that butyrate metabolism is activated in HCC patients compared with healthy individuals. Butyrate levels are lower in the plasma of HCC patients by gas chromatography-mass spectrometry (GC-MS) analysis. Butyrate supplementation or depletion of short-chain Acyl-CoA dehydrogenase (SCAD) gene (ACADS), encoding a key enzyme for butyrate metabolism, significantly inhibits HCC proliferation and metastasis. The profiling analysis of genes upregulated by butyrate supplementation or ACADS knockdown reveals that calcium signaling pathway is activated, leading to dysregulation of intracellular calcium homeostasis and production of reactive oxygen species. Butyrate supplementation improves the therapy efficacy of a tyrosine kinase inhibitor sorafenib. On the basis of these findings, we developed butyrate and sorafenib coencapsulated mPEG-PLGA-PLL nanoparticles coated with anti-GPC3 antibody (BS@PEAL-GPC3) to prolong the retention time of drugs and enhance drug targeting, leading to high anticancer efficacy. BS@PEAL-GPC3 nanoparticles significantly reduce HCC progression. In addition, BS@PEAL-GPC3 nanoparticles display excellent HCC targeting with excellent safety. CONCLUSIONS: In conclusion, our findings provide new insight into the mechanism by which the gut microbial metabolites inhibit HCC progression, suggesting a translatable therapeutics approach to enhance the clinical targeted therapeutic efficacy.
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Antineoplásicos , Butiratos , Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Sorafenibe , Butiratos/farmacologia , Cálcio/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Homeostase , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.
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Injúria Renal Aguda , Curcumina , Nanopartículas , Camundongos , Animais , Curcumina/farmacologia , Cisplatino/efeitos adversos , Peróxido de Hidrogênio , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Antioxidantes/farmacologiaRESUMO
Background: Chinese medicine (CM) syndrome differentiation is one of the fundamental principles that guide the practice of Chinese herbal medicine (CHM). CHM has been widely used among breast cancer patients. Contemporary literature varies in syndrome diagnosis, and there is a need to standardize syndrome differentiation according to the different stages of breast cancer treatment. This multicenter clinical study aims to identify the CM syndromes and the clinical signs and symptoms in women with early breast cancer. Methods: Participants who met the inclusion and exclusion criteria were interviewed during the five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Patient demographic data and CM syndrome (as recorded by the treating CM clinicians in medical records) were gathered. Signs and symptoms were analyzed using descriptive statistics to derive the standardized CM syndromes using hierarchical cluster analysis. Results: The analysis included 964 interviews with 620 participants enrolled between April 29, 2020 and May 30, 2021 from eight participating hospitals in China. The two most frequent syndromes recorded in medical records were dual deficiency of qi and blood, and dual deficiency of qi and yin during all but the preoperative stage. The symptoms of lassitude, lack of strength, and insomnia were common in all but the preoperative stage. Cluster analysis identified two clusters in the preoperative stage that most closely resembled the syndrome diagnoses of liver stagnation with congealing phlegm, and dual deficiency of the liver and kidney. Two clusters-dual deficiency of qi and blood, and dual deficiency of qi and yin-were common to multiple treatment stages. The syndrome cluster of spleen and stomach disharmony existed in both the postoperative and chemotherapy stages. Cluster analysis of the radiation therapy stage identified the unique syndrome of yin deficiency with fire toxin, while the endocrine therapy included the syndromes of liver depression and kidney deficiency. Conclusions: This multicenter clinical study showed consistency between results from cluster analysis and the most common syndromes recorded in the medical records. Findings from this clinical study will be further validated in a Delphi study to standardize CM syndromes for various stages of breast cancer treatment. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier ChiCTR2000032497.
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Tumor phototherapies are light-mediated tumor treatment modalities, which usually refer to tumor photothermal therapy (PTT) and photodynamic therapy (PDT). Due to the outstanding spatial-temporal control over treatment through light irradiation, tumor phototherapies display extremely low side effects during treatment and are believed to be a tumor treatment method with a clinical translation potential. However, current tumor phototherapy nanoplatforms face obstacles, including light irradiation-induced skin burning, tumor hypoxia microenvironments, limited light penetration depth, et al. Therefore, one important research direction is developing a tumor phototherapy nanoplatform with multifunctionality and enhanced pharmacological effects to overcome the complexity of tumor treatment. On the other hand, cyclodextrins (CDs) are starch-originated circular oligosaccharides with negligible toxicity and have been used to form supermolecular nanostructures through a host-guest interaction between the inner cavity of CDs and functional biomolecules. In the past few years, numerous studies have focused on CD-based multifunctional tumor phototherapy nanoplatforms with an enhanced photoeffect, responsive morphological transformation, and elevated drug bioavailability. This review focuses on the preparation methods of CD-based tumor phototherapy nanoplatforms and their unique physiochemical properties for improving anti-tumor pharmacological efficacy.
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Background: Chinese medicine (CM) has been widely used for women's health, including those with early breast cancer. Contemporary literature varies in descriptions of the CM syndromes that are critical for determining CM treatment options for breast cancer patients. However, the corresponding syndromes have not been standardized to align with the conventional medicine treatment stages. This review aimed to address this knowledge gap to enhance the quality and consistency of CM interventions for early breast cancer patients. Methods: In total, eight Chinese and English language databases were searched, and textbooks and clinical care documents were gathered. Sources were classified according to five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Descriptive statistics were used to examine the syndromes, and hierarchical cluster analysis was conducted to investigate clusters of signs and symptoms. Results: The CM syndrome of dual deficiency of qi and Blood was one of the most common syndromes across all treatment stages, whereas lack of strength and lassitude were the most common clinical presentations throughout all stages, except the preoperative stage. Cluster analyses identify three or four syndromes in each treatment stage. Cluster results for the preoperative stage were: Blood stasis, Liver depression and qi stagnation, and Kidney yin deficiency. Dual deficiency of qi and Blood existed at different stages except for the preoperative stage. In the postoperative stage and chemotherapy stages, some symptoms were categorized into clusters that related to the Spleen and Stomach. Syndromes such as yin deficiency with fire toxin and yin deficiency with fluid depletion were unique to the radiation therapy stage. Clusters for endocrine therapy stage included the dual deficiency of Spleen and Kidney, Liver depression and qi stagnation, and Kidney yin deficiency. Conclusions: Systematic review of the contemporary literature for early breast cancer revealed that the most frequently seen CM syndromes and cluster results have some similarities but some important distinctions. Clinical data are needed to confirm whether the syndromes described in contemporary literature reflect those seen in women with early breast cancer.
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Neoplasias da Mama , Medicina Tradicional Chinesa , Neoplasias da Mama/terapia , Análise por Conglomerados , Feminino , Humanos , Síndrome , Deficiência da Energia Yin/diagnóstico , Deficiência da Energia Yin/terapiaRESUMO
Ovarian cancer has been the most lethal gynaecological malignancy worldwide. Additionally, triptolide is an active substance that has been extracted from the Chinese herbal medicine T. wilfordii Hook F. , which possesses anti-tumor, immunomodulatory and anti-inflammatory properties. In recent years, TP has attracted increasing attention because of its broad-spectrum efficient anti-tumor activity. Nevertheless, its clinical utility is limited due to its severe side effects. In this study, we constructed an exosome-encapsulated TP targeted drug delivery systems, studying its anti-tumor effects and mechanisms in vivo and in vitro . We observed that compared with free TP, TP-Exos significantly enhanced anti-ovarian cancer effects and reduce toxicity to important organs. We further demonstrated that TP-Exos induced apoptosis of ovarian cancer cells, regulated tumor immunity by activating the mitochondrial apoptosis pathway and selectively inhibited M2 tumor-associated macrophages and their tumor-promoting mediators in the tumor microenvironment. In summary, TP-Exos are a promising treatment for ovarian cancer.
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Diterpenos , Exossomos , Neoplasias Ovarianas , Fenantrenos , Apoptose , Compostos de Epóxi , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Microambiente TumoralRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive among breast cancer subtypes with the worst prognosis. Ginger is widely used in pharmaceuticals and as food. Its anticancer properties are known, but the mechanism is still unclear. [10]-Gingerol is one of the main phenolic compounds isolated from ginger. Studying the biological effects of [10]-Gingerol is of great significance to understand the efficacy of ginger. METHODS: In this study, the therapeutic effects of [10]-Gingerol on TNBC cells were studied using network pharmacology, molecular docking, and in vitro experiments, and the target and mechanism of action were explained. RESULTS: A total of 48 targets of ginger for the treatment of TNBC were found. These targets might interfere with the growth of TNBC by participating in many pathways, such as endocrine resistance, progesterone-mediated oocyte maturation, estrogen signaling pathway, and cellular senescence. Prognostic analyses indicated that the JUN, FASN, ADRB2, ADRA2A, and PGR were the hub genes, while molecular docking predicted the stable binding of ADRB2 protein with drug compounds. Additionally, [10]-Gingerol could induce apoptosis by regulating the caspase activation. CONCLUSIONS: [10]-Gingerol affects the growth of TNBC through multiple action targets and participating in multiple action pathways. ADRB2 and apoptosis pathways might be important target pathways for [10]-Gingerol in the treatment of TNBC.
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BACKGROUND/AIMS: Alpinia zerumbet (Pers.) Burtt. et Smith has been used as a flavor additive in food and a traditional medicine for centuries, especially in Guizhou Province, China, and it prolongs people's lives with multiple beneficial effects. Thus, one of the aims of this review was to expound the chemical constituents of this plant, especially its fruits. Since cardiovascular diseases, including atherosclerosis, pose a health threat to humans, another aim was to expound the possible mechanisms of its potential use as an herbal medication for atherosclerosis. METHODS: In this study, 10 reports are cited to expound the potential bioactive compounds. Moreover, 33 reports explain the antihypertensive and antiatherosclerotic effects of the plant by ameliorating inflammation and endothelial dysfunction, increasing vasodilation, improving hyperlipidemia, downgrading the glucose status, and working as an antioxidant. RESULTS: A. zerumbetis rich in terpenes, essential oils, flavonoids, polyphenolics, and sterols. Pharmacological experiments showed that A. zerumbet has antioxidative and anti-inflammatory effects on the NF-κB signaling pathway and can ameliorate oxidative stress in the NOS-NO signaling pathway. Moreover, A. zerumbet demonstrates antihypertensive effects by accelerating vasorelaxant response and increasing 3T3-L1 intracellular cAMP, which has promising antiobesity properties, as well as hypolipidemic and anti-diabetic complication effects. CONCLUSIONS: A. zerumbet has potential functions and applications in the prevention of atherosclerosis, but further studies are required before clinical trials.
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Alpinia/química , Aterosclerose/tratamento farmacológico , Extratos Vegetais/farmacologia , Preparações de Plantas , Células 3T3-L1 , Animais , Fármacos Antiobesidade/farmacologia , Antioxidantes/farmacologia , Glicemia/química , Humanos , Hiperlipidemias/tratamento farmacológico , Concentração Inibidora 50 , Cinética , Masculino , Medicina Tradicional Chinesa , Mesocricetus , Camundongos , Óxido Nítrico Sintase , Óleos Voláteis/química , Estresse Oxidativo/efeitos dos fármacos , Preparações de Plantas/uso terapêutico , Ratos , Fatores de RiscoRESUMO
Transcription factor Yin Yang 1 (YY1) is upregulated in multiple tumors and plays essential roles in tumor proliferation and metastasis. However, the function of YY1 in breast cancer stemness remains unclear. Herein, we found that YY1 expression was negatively correlated with the overall survival and relapse-free survival of breast cancer patients and positively correlated with the expression of stemness markers in breast cancer. Overexpression of YY1 increased the expression of stemness markers, elevated CD44+CD24- cell sub-population, and enhanced the capacity of cell spheroid formation and tumor-initiation. In contrast, YY1 knockdown exhibited the opposite effects. Mechanistically, YY1 decreased microRNA-873-5p (miR-873-5p) level by recruiting histone deacetylase 4 (HDAC4) and HDAC9 to miR-873-5p promoter and thus increasing the deacetylation level of miR-873-5p promoter. Sequentially, YY1 activated the downstream PI3K/AKT and ERK1/2 pathways, which have been confirmed to be suppressed by miR-873-5p in our recent work. Moreover, the suppressed effect of YY1/miR-873-5p axis on the stemness of breast cancer cells was partially dependent on PI3K/AKT and ERK1/2 pathways. Finally, it was found that the YY1/miR-873-5p axis is involved in the chemoresistance of breast cancer cells. Our study defines a novel YY1/miR-873-5p axis responsible for the stemness of breast cancer cells.
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Deoxynivalenol (DON) is one of the most prevalent food- and feed-associated mycotoxins. It frequently contaminates agricultural commodities and poses serious threats to human and animal health and leads to tremendous economic losses globally. Much attention has been paid to using microorganisms to detoxify DON. In this study, a Bacillus licheniformis strain named YB9 with a strong ability to detoxify DON was isolated and characterized from a moldy soil sample. YB9 could degrade more than 82.67% of 1 mg/L DON within 48 h at 37 °C and showed strong survival and DON degradation rate at simulated gastric fluid. The effects of YB9 on mice with DON intragastrical administration were further investigated by biochemical and histopathological examination and the gut microbiota was analyzed by 16S rRNA Illumina sequencing technology. The results showed that DON increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine (Cr), decreased those of immunoglobulin G (IgG) and IgM in serum, and resulted in severe pathological damage of the liver, kidney, and spleen. By contrast, YB9 supplementation obviously inhibited or attenuated the damages caused by DON in mice. In addition, YB9 addition repaired the DON-induced dysbiosis of intestinal flora, characterized by recovering the balance of Firmicutes and Bacteroidetes to the normal level and decreasing the abundance of the potentially harmful bacterium Turicibacter and the excessive Lactobacillus caused by DON. Taken together, DON-degrading strain YB9 might be used as potential probiotic additive for improving food and feed safety and modulating the intestinal microbial flora of humans and animals.
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Bacillus licheniformis/isolamento & purificação , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Tricotecenos/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bacillus licheniformis/metabolismo , Biodegradação Ambiental , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Suplementos Nutricionais , Disbiose/sangue , Imunoglobulina G/sangue , Fígado/efeitos dos fármacos , Fígado/microbiologia , Fígado/patologia , Camundongos Endogâmicos BALB C , Microbiologia do Solo , Tricotecenos/análiseRESUMO
Berberine is a widely used antimicrobial agent in clinic. However, a high dosage is often required due to its low lipophilicity and bioavailability. The current study explores the structural modifications of berberines with potentially lipophilic aryl groups to address this problem. A series of 15 9-O-aryl-substituted berberines (3a-o) and one 9-O-phenylene-bridged berberine dimer (5) was synthesized by copper-catalyzed cross-coupling of tetrahydroberberrubine and aryl iodides, followed by oxidation with I2.
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The chronic infections by pathogenic Pseudomonas aeruginosa (P. aeruginosa) remain to be properly addressed. In particular, for drug-resistant strains, limited medication is available. An in vivo pneumonia model induced by a clinically isolated aminoglycoside resistant strain of P. aeruginosa is developed. Tobramycin clinically treating P. aeruginosa infections is found to be ineffective to inhibit or eliminate this drug-resistant strain. Here, a newly developed non-antibiotics based nanoformulation plus near-infrared (NIR) photothermal treatment shows a remarkable antibacterial efficacy in treating this drug-resistant pneumonia. The novel formulation contains 50-100 nm long nanorods decorated with two types of glycomimetic polymers to specifically block bacterial LecA and LecB lectins, respectively, which are essential for bacterial biofilm development. Such a 3D display of heteromultivalent glycomimetics on a large scale is inspired by the natural strengthening mechanism for the carbohydrate-lectin interaction that occurs when bacteria initially infects the host. This novel formulation shows the most efficient bacteria inhabitation and killing against P. aeruginosa infection, through lectin blocking and the near-infrared-light-induced photothermal effect of gold nanorods, respectively. Collectively, the novel biomimetic design combined with the photothermal killing capability is expected to be an alternative treatment strategy against the ever-threatening drug-resistant infectious diseases when known antibiotics have failed.
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Materiais Biomiméticos , Hipertermia Induzida/métodos , Fototerapia/métodos , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa , Células A549 , Abscesso/tratamento farmacológico , Abscesso/patologia , Adesinas Bacterianas/metabolismo , Animais , Biofilmes , Farmacorresistência Bacteriana , Escherichia coli , Compostos de Ouro , Humanos , Lactose/análogos & derivados , Lectinas/antagonistas & inibidores , Lectinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanotubos , Pneumonia Bacteriana/patologia , Pneumonia Bacteriana/terapia , Ácidos Polimetacrílicos , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/metabolismoRESUMO
The CaCO3 encapsulated liposome with pH sensitivity is an efficient carrier for the delivery of chemotherapeutic drugs. Herein, we provided an innovative method that take advantage of a W/O emulsion to prepare CaCO3 encapsulated liposomes for the delivery of curcumin. The liposomes with both CaCO3 and curcumin encapsulated (LCC) showed high sensitivity to reduced pH (the environment of lysosomes). Due to the inherent pH sensitivity of CaCO3, LCC swelled and released the encapsulated curcumin rapidly in acidic medium. The lysosome escape capability and promoted accumulation of curcumin in the cytosol from LCC was verified with respect to that of curcumin loaded liposomes (CLIPO). Despite the similar cytotoxicity within curcumin preparations in vitro at high concentration, LCC exhibited optimal antitumor effect in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal cancer model, which was attributed to the long circulation time and efficient intracellular delivery of curcumin from LCC. It is suggested that the solubility and cytosolic delivery of curcumin are greatly improved by LCC, which accounts for the increased pharmacodynamic effect of curcumin. Thus, the CaCO3 encapsulated liposomes developed in this study is an ideal carrier for the hydrophobic drugs in potential clinical application.
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Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacocinética , Carbonato de Cálcio , Linhagem Celular Tumoral , Neoplasias do Colo/induzido quimicamente , Curcumina/farmacocinética , Citosol/metabolismo , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Emulsões , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óleos , Ratos , Ratos Sprague-Dawley , ÁguaRESUMO
OBJECTIVE: To investigate the effect of Jianpi Bushen (JPBS) formula on aromatase inhibitor (AI)-associated bone loss after menopause. METHODS: Six-month-old female rats were randomly divided into 6 groups: a sham group, an ovariectomized (OVX) group, an OVX treated with exemestane and 3 OVX groups each treated with a different dose of JPBS formula. Bone mineral density (BMD) at the lumbar vertebrae, histology, bone markers and serum levels of estrogen were assessed. Furthermore, a cohort study was conducted in 130 postmenopausal women with breast cancer that had undergone treatment with AIs. The subjects were given JPBS + caltrate D or caltrate D only, administered orally. BMD at the lumbar vertebrae and femoral neck and bone markers were evaluated in both control and herbal treatment groups at baseline and 12 months. RESULTS: Experimental results indicated that a high dose of JPBS significantly increased the trabecular bone area percentage (Tb.Ar %) and broadened the trabecular thickness (Tb.Th). The JPBS formula enriched the carboxyterrninal propeptide of type ipmcollagen and increased serum estrogen level significantly. The clinical investigation revealed that bone loss was decreased in the group treated with JPBS vs control (BMD T score at lumbar vertebrae, 3.9% increased vs 14.58% decreased, respectively, P = 0.004 and BMD T score on femoral neck, 1.8% decreased vs 22.45% decreased, respectively, P = 0.008). Besides, JPBS formula elevated N- middle osteocalcin and decreased type I collagen cross-linked C-terminal telopeptide. CONCLUSION: JPBS formula prevented aromatase-inhibitor-associated bone loss after menopause by inhibiting bone resorption and promoting bone formation.
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Inibidores da Aromatase/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Absorciometria de Fóton , Idoso , Animais , Inibidores da Aromatase/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Estrogênios/sangue , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Pessoa de Meia-Idade , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/fisiopatologia , Estudos Prospectivos , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The aim of this study was to establish the standardization of syndrome differentiation of operative breast cancer treated with Traditional Chinese Medicine (TCM) by the modified Delphi method. METHOD: A literature search for standardization of syndrome differentiation of operative breast cancer was conducted and eligible articles were identified in indexed databases from 1982 to 2013. We carried out two rounds of investigation between March and October 2013 and organized 20 experts who focused on TCM or integrative medicine in breast cancer research. Experts' judgments were collected via posted questionnaires or e-mail. A final evaluation was carried out after the end of both rounds. RESULT: The response ratio of the 1st round investigation reached 100%, and two experts were excluded due to the uncompleted questionnaire. The 2nd round investigation was completed by 18 experts in the 1st round panel board. In both rounds, the experts agreed that the stage of breast cancer defined by TCM could be divided into the perioperation period, the perichemotherapy period, the periradiotherapy period, and the consolidation period. CONCLUSION: We identified the feasibility and reasonability to establish the standardization of syndrome differentiation of operative breast cancer. According to the suggestions from experts in our Delphi study, we preliminarily established the TCM standard of syndrome differentiation based on different treatment stages of operative breast cancer.
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Neoplasias da Mama/cirurgia , Técnica Delphi , Medicina Tradicional Chinesa , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Prova Pericial , Feminino , Humanos , Radiografia , Padrões de Referência , Síndrome , Fatores de TempoRESUMO
OBJECTIVE: To analysis liposoluble constituents of Holotrichia diomphalia by GC-MS and measure their anti-inflammatory and analgesic activities. METHODS: The composition of liposoluble constituents were determined by GC-MS. The dimethylbenzene-induced mice inflammatory models were established. The pain models were obtained by hot plate and acetic acid in mice. RESULTS: Twenty-two components were identified from the petroleum ether extract of Holotrichia diomphalia. The major components were oleic acid, palmitic acid and palmitoleic acid. The petroleum ether extract was able to significantly inhibit the mice ear edema induced by dimethyl-benzene. The pain in mice caused by acetic acid and hot plate were evidently suppressed by the petroleum ether extract. CONCLUSION: The petroleum ether extract of Holotrichia diomphalia has obvious anti-inflammation and analgesic effects.