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Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.
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Perda do Osso Alveolar , Berberina , Regeneração Óssea , Fator Estimulador de Colônias de Macrófagos , Macrófagos , Células-Tronco Mesenquimais , Berberina/farmacologia , Humanos , Animais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Regeneração Óssea/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Ratos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Perda do Osso Alveolar/metabolismo , Masculino , Ratos Sprague-Dawley , Osteogênese/efeitos dos fármacos , Células Cultivadas , Proteínas Proto-Oncogênicas c-akt/metabolismo , CamundongosRESUMO
OBJECTIVE: Metabolic-associated fatty liver disease (MAFLD) is the most prevalent liver disease, whereas type 2 diabetes mellitus (T2DM) is considered an independent risk factor for MAFLD incidence. Taohe Chengqi decoction (THCQ) is clinically prescribed for T2DM treatment; however, the hepatoprotective effect of THCQ against MAFLD is still unknown. This study intended to elucidate the therapeutic effect of THCQ on T2DM-associated MAFLD and to investigate the underlying mechanisms. METHODS: THCQ lyophilized powder was prepared and analyzed by UHPLC-MS/MS. A stable T2DM mouse model was established by high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. The T2DM mice were administered THCQ (2.5 g/kg or 5 g/kg) to explore the pharmacological effects of THCQ on T2DM-associated MAFLD. Liver tissue transcriptome was analyzed and the participatory roles of PPARα/γ pathways were verified both in vivo and in vitro. Serum metabolome analysis was used to explore the metabolome changes and skeletal muscle branched chain amino acid (BCAA) catabolic enzymes were further detected. Moreover, an AAV carrying BCKDHA shRNA was intramuscularly injected to verify the impact of THCQ on skeletal muscle BCAA catabolism and the potential therapeutic outcome on hepatic steatosis. RESULTS: THCQ improved hepatic steatosis in MAFLD. RNA-sequencing analysis showed dysregulation in the hepatic PPARγ-related fatty acid synthesis, while PPARα-dependent fatty acid oxidation was elevated following THCQ treatment. Interestingly, in vitro analyses of these findings showed that THCQ had minor effects on fatty acid oxidation and/or synthesis. The metabolomic study revealed that THCQ accelerated BCAA catabolism in the skeletal muscles, in which knockdown of the BCAA catabolic enzyme BCKDHA diminished the THCQ therapeutic effect on hepatic steatosis. CONCLUSION: This study highlighted the potential therapeutic effect of THCQ on hepatic steatosis in MALFD. THCQ upregulated fatty acid oxidation and reduced its synthesis via restoration of PPARα/γ pathways in HFD/STZ-induced T2DM mice, which is mediated through augmenting BCKDH activity and accelerating BCAA catabolism in the skeletal muscles. Overall, this study provided in-depth clues for "skeletal muscles-liver communication" in the therapeutic effect of THCQ against hepatic steatosis. These findings suggested THCQ might be a potential candidate against T2DM-associated MAFLD.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Aminoácidos de Cadeia Ramificada/metabolismo , Aminoácidos de Cadeia Ramificada/farmacologia , PPAR alfa , Espectrometria de Massas em Tandem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Músculo Esquelético/metabolismo , Ácidos GraxosRESUMO
OBJECTIVE: Sacral neuromodulation (SNM) has emerged as an effective therapy for refractory lower urinary tract dysfunction (LUTD). Remote programming holds promise in addressing the time and economic burdens associated with outpatient programming, especially for patients in the observation period following Stage I implant surgery (where the lead is implanted first without the pulse generator). The study aimed to explore the effectiveness and patient satisfaction of remote programming for Stage I SNM patients, and analyze the benefits patients gain from remote programming. METHODS: This prospective study was conducted at multiple high-level clinical SNM centres in China. Patients requiring SNM implantation were enroled and divided into two groups based on patient preference: remote programming (RP) group and outpatient control (OC) group. Patient attitudes toward RP were assessed through questionnaires, and the degree of symptom improvement was compared between the two groups to explore the usability of RP. RESULTS: A total of 63 participants from 6 centres were included in the study, with 32 belonging to the RP group. The remote programming system presents a high level of usability (98%) and willingness (satisfaction rate: 96.83%) in result of questionnaire. RP showed a significant advantage in improving patients' score of ICSI/ICPI (medianΔICSI/ICPI RP vs. OC= -13.50 vs -2, P =0.015). And slightly ameliorate urinary symptoms such as pain (medianΔVAS RP vs. OC= -1 vs 0, P = 0.164) and urgency (medianΔOBASS -2.5 vs. -1, P = 0.,229), but the difference was not statistically significant. RP did not significantly impact the quality of life of patients ( P =0.113), so do the rate of phase-two conversion ( P = 0.926) or programming parameters. CONCLUSION: To the best of our knowledge, the presented study is the first multicenter research focusing on the remote programming of Stage I SNM patients. Through the clinical implementation and patient feedback, we demonstrate that remote programming is not inferior to in-person programming in terms of success rate, effectiveness, safety, and patient satisfaction.
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Terapia por Estimulação Elétrica , Estudos de Viabilidade , Satisfação do Paciente , Humanos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Terapia por Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/instrumentação , Idoso , Resultado do Tratamento , Inquéritos e Questionários , Plexo Lombossacral , Sintomas do Trato Urinário Inferior/terapia , China , Sacro/inervaçãoRESUMO
Targeting nutrient metabolism has been proposed as an effective therapeutic strategy to combat breast cancer because of its high nutrient requirements. However, metabolic plasticity enables breast cancer cells to survive under unfavorable starvation conditions. The key mammalian target regulators rapamycin (mTOR) and hypoxia-inducible-factor-1 (HIF-1) tightly link the dynamic metabolism of glutamine and glucose to maintain nutrient flux. Blocking nutrient flow also induces autophagy to recycle nutrients in the autophagosome, which exacerbates metastasis and tumor progression. Compared to other common cancers, breast cancer is even more dependent on mTOR and HIF-1 to orchestrate the metabolic network. Therefore, we develop a cascade-boosting integrated nanomedicine to reprogram complementary metabolism coupled with regulators in breast cancer. Glucose oxidase efficiently consumes glucose, while the delivery of rapamycin inside limits the metabolic flux of glutamine and uncouples the feedback regulation of mTOR and HIF-1. The hydroxyl radical generated in a cascade blocks the later phase of autophagy without nutrient recycling. This nanomedicine targeting orchestrated metabolism can disrupt the coordination of glucose, amino acids, nucleotides, lipids, and other metabolic pathways in breast cancer tissues, effectively improving the durable antitumor effect and prognosis of breast cancer. Overall, the cascade-boosting integrated system provides a viable strategy to address cellular plasticity and efficient enzyme delivery.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Glutamina/metabolismo , Biomimética , Nanomedicina , Serina-Treonina Quinases TOR/metabolismo , Sirolimo , Glucose/metabolismoRESUMO
In this study, sediment organic phosphorus (OP) and organic carbon (OC) in Lake Taihu, China, as well as their relationships, were analyzed during the outbreak and decline of algal blooms (ABs) over a five-month field study. The results showed synchronous temporal changes in the sediment OP and OC contents with the development of ABs. In addition, there was a significant positive correlation between the sediment OP and OC (p < 0.01), suggesting simultaneous deposition and consumption during the ABs outbreak. The sediment OP and OC contents decreased significantly at the early and last stages of the ABs outbreak and increased at the peak of the ABs outbreak and during the ABs decline. These temporal variation patterns suggest that the sediment OC and OP contents did not consistently increase during the ABs outbreak, even though algae are an important source of organic matter in sediments. The depletion or enrichment of OC and OP in sediments may also depend on the scale of the ABs outbreak. The obtained results revealed significant differences in the sediment OC and OP contents between the months (p < 0.05). In addition, OP in the sediments was dominated by orthophosphate diester (phospholipids and DNA-P) and orthophosphate monoester during the ABs outbreak and decline, respectively. The active OC contents and proportions in the sediments in the ABs outbreak were significantly lower than those observed in the ABs decline period, demonstrating the significant impacts of the ABs outbreak and decline on the sediment OC and OP in Lake Taihu.
Assuntos
Lagos , Poluentes Químicos da Água , Fósforo/análise , Carbono , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Eutrofização , China , FosfatosRESUMO
Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is a need to understand the targets related to insomnia, in order to develop innovative therapies and new compounds. Recently, increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia. Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain. In this review, the role of 5-hydroxytryptamine (5-HT) in insomnia development is summarized, while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes, in order to provide reference for subsequent research.
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Plantas Medicinais , Distúrbios do Início e da Manutenção do Sono , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Sono , Humanos , AnimaisRESUMO
A supercritical fluid carbon dioxide (SF-CO2) extraction method was used to obtain the optimum process for extracting yellow horn seed oil. The anti-fatigue and antioxidant properties of the extracted oil were investigated through animal experiments. The optimum process conditions for SF-CO2 extraction of the yellow horn oil were 40 MPa, 50 °C and 120 min, with an extraction yield of 31.61%. The high-dose group of yellow horn oil could significantly increase the weight-bearing swimming time, the hepatic glycogen (HG) content and decrease the lactic acid (LA) content and blood urea nitrogen (BUN) content (p < 0.05) in mice. Moreover, it improved the antioxidant ability by reducing the malondialdehyde (MDA) content (p < 0.01) and raising the glutathione reductase (GR) content and superoxide dismutase (SOD) content (p < 0.05) in mice. Yellow horn oil has the effects of being an anti-fatigue and antioxidant substance, which provides a basis for its further utilization and development.
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Cromatografia com Fluido Supercrítico , Sapindaceae , Camundongos , Animais , Antioxidantes/farmacologia , Dióxido de Carbono , Óleos de Plantas/farmacologia , Sementes , Superóxido DismutaseRESUMO
Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)-treated mice and found that oral gavage with butyrate-producing bacteria (C. butyricum) and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen-specific CD4+ T cells and IFN-γ-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138+ PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. IMPORTANCE The gut microbiome plays many crucial roles in the maintenance of immune homeostasis. Alteration of the gut microbiome and metabolites has been shown to impact vaccine efficacy. SCFAs can act as an energy source for B-cells, thereby promoting both mucosal and systemic immunity in the host by inhibiting HDACs and activation of GPR receptors. This study investigates the impact of orally administered butyrate, an SCFA, on the immunogenicity of rabies vaccines in Vanco-treated mice. The results showed that butyrate ameliorated humoral immunity by facilitating the generation of plasma cells via the Akt-mTOR in Vanco-treated mice. These findings unveil the impact of SCFAs on the immune response of the rabies vaccine and confirm the crucial role of butyrate in regulating immunogenicity to rabies vaccines in antibiotic-treated mice. This study provides a fresh insight into the relationship of microbial metabolites and rabies vaccination.
Assuntos
Vacina Antirrábica , Raiva , Camundongos , Animais , Raiva/prevenção & controle , Plasmócitos , Imunidade Humoral , Vancomicina/farmacologia , Proteínas Proto-Oncogênicas c-akt , Anticorpos Antivirais , Serina-Treonina Quinases TOR , Ácidos Graxos Voláteis , ButiratosRESUMO
Aggregation-induced emission luminogens (AIEgens) are of great importance in optoelectronics and biomedical fields. However, the popular design philosophy by combining rotors with traditional fluorophores limits the imagination and structural diversity of AIEgens. Inspired by the fluorescent roots of the medicinal plant Toddalia asiatica, we discovered two unconventional rotor-free AIEgens, 5-methoxyseselin (5-MOS) and 6-methoxyseselin (6-MOS). Interestingly, a slight structural difference of the coumarin isomers leads to completely contrary fluorescent properties upon aggregation in aqueous media. Further mechanism investigation indicates that 5-MOS forms different extents of aggregates with the assistance of protonic solvents, leading to electron/energy transfer, which is responsible for its unique AIE feature, i.e., reduced emission in aqueous media but enhanced emission in crystal. Meanwhile, for 6-MOS, the conventional restriction of the intramolecular motion (RIM) mechanism is responsible for its AIE feature. More interestingly, the unique water-sensitive fluorescence property of 5-MOS enables its successful application for wash-free mitochondria imaging. This work not only demonstrates an ingenious tactic to seek new AIEgens from natural fluorescent species but also benefits the structure design and application exploration of next-generation AIEgens.
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BACKGROUND: Associations between blood pressure (BP) with age at onset of Huntington's disease (HD) have reported inconsistent findings. We used Mendelian randomization (MR) to assess effects of BP and lowering systolic BP (SBP) via the genes encoding targets of antihypertensive drugs on age at onset of HD. METHODS: Genetic variants from genome-wide association studies(GWAS) of BP traits and BP-lowering variants in genes encoding antihypertensive drugs targets were extracted. Summary statistics for age at onset of HD were retrieved from the GWAS meta-analysis of HD residual age at onset from the GEM-HD Consortium included 9064 HD patients of European ancestry (4417 males and 4,647 females). MR estimates were calculated using the inverse variance weighted method, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. RESULTS: Genetically predicted SBP or diastolic BP increase was associated with a later age at onset of HD. However, after SBP/DBP was present as a covariate using multivariable MR method, no significant causal association was suggested. A 10-mm Hg reduction in SBP through variants in genes encoding targets of calcium channel blockers (CCB) was associated with an earlier age at onset of HD (ß=-0.220 years, 95% CI =-0.337 to -0.102, P = 2.42 × 10- 4). We did not find a causal association between angiotensin converting enzyme inhibitors and ß-blockers with the earlier HD onset. No heterogeneity and horizontal pleiotropy were identified. CONCLUSIONS: This MR analysis provided evidence that genetically determined SBP lowering through antihypertensive drugs might be associated with an earlier age at onset of HD. The results may have a potential impact on management of hypertension in the pre-motor-manifest HD population.
Assuntos
Doença de Huntington , Hipertensão , Feminino , Masculino , Humanos , Anti-Hipertensivos/uso terapêutico , Idade de Início , Estudo de Associação Genômica Ampla , Doença de Huntington/tratamento farmacológico , Doença de Huntington/genética , Hipertensão/tratamento farmacológico , Hipertensão/genéticaRESUMO
Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is easily found in the environment. Excessive daily exposure of it may lead to an increased risk of cardiovascular disease (CVD). Lycopene (LYC), as a natural carotenoid, has been shown to have the potential to prevent CVD. However, the mechanism of LYC on cardiotoxicity caused by DEHP exposure is unknown. The research was aimed to investigate the chemoprotection of LYC on the cardiotoxicity caused by DEHP exposure. Mice were treated with DEHP (500 mg/kg or 1,000 mg/kg) and/or LYC (5 mg/kg) for 28 d by intragastric administration, and the heart was subjected to histopathology and biochemistry analysis. The results indicated that DEHP caused cardiac histological alterations and enhanced the activity of cardiac injury indicators, and interfered with mitochondrial function and activating mitophagy. Notably, LYC supplementation could inhibit DEHP-induced oxidative stress. The mitochondrial dysfunction and emotional disorder caused by DEHP exposure were significantly improved through the protective effect of LYC. We concluded that LYC enhances mitochondrial function by regulating mitochondrial biogenesis and dynamics to antagonize DEHP-induced cardiac mitophagy and oxidative stress.
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Dietilexilftalato , Camundongos , Animais , Licopeno/farmacologia , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Mitofagia , Estresse Oxidativo , Mitocôndrias/metabolismo , HomeostaseRESUMO
The mechanical grinding scale of insoluble dietary fiber has an important influence on bread staling quality. We investigated the effects of buckwheat hull (BWH) powder at tissue-scale (500-100 µm) and cell-scale (50-10 µm) on the physical and structural changes of bread during storage. The addition of tissue-scale BWH had little effect on loaf volume and crumb firmness of bread, while that of cell-scale BWH significantly decreased specific volume and baking loss, and resulted in higher bread firmness, compared with the control (100 % wheat bread). The effect of cell-scale BWH on delaying amylopectin retrogradation and starch recrystallization during bread storage was superior to that of tissue-scale BWH. Tissue-scale BWH made the gas cell structure of the crumb coarse and open, promoting the evaporation of water during storage. BWH at the cell-scale had a stronger water-binding ability than tissue-scale BWH, which restricted the loss of water, inhibiting bread staling.
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Pão , Fagopyrum , Amilopectina/química , Amido/química , Água/químicaRESUMO
Cisplatin (DDP)-based chemotherapy is the first-line regimen for advanced non-small cell lung cancer (NSCLC) patients. However, advanced NSCLC patients may have innate resistance to DDP or develop resistance during DDP treatment. We investigated a natural compound, arteannuin B (Art B), for its potential effects on DDP resistance in NSCLC. Art B was isolated from Artemisia annua by chromatographic purification and spectral elucidation. The activities of Art B on DDP-mediated effects were examined using in vitro and in vivo assays. We observed significant correlations in T stage, clinical stage, chemotherapy resistance and poor survival of NSCLC patients with low Cx43 expression. Art B enhanced the effectiveness of cisplatin by increasing Cx43 expression in normal and DDP-resistant NSCLC cells. Art B also increased DDP uptake through up-regulating Cx43. The combination of DDP and Art B showed better therapeutic effect than individual treatments both in vitro and in vivo. Art B increased intracellular Fe[Formula: see text] level, promoted calcium influx, and activated gap junction and MAPK pathways, which might contribute to Art B-mediated effects. Art B may serve as a new drug candidate to enhance the antitumor effect of DDP on NSCLC.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Conexina 43/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Sistema de Sinalização das MAP QuinasesRESUMO
BACKGROUND: The combination of photothermal therapy (PTT) and chemotherapy has proven to be a promising strategy for cancer treatment. Various nanomaterials have shown great potential in combination therapy, including gold, graphene oxide, iron oxide, and other nanoparticles. However, their undefinable toxicity in vivo greatly slowed down their development for clinical applications. OBJECTIVE: The present work aimed to develop a multifunctional nanoparticle for chemo-photothermal therapy composed of acknowledged biocompatible materials. METHODS: A novel biocompatible nanoparticle (HIT-NPs) was self-assembled through the intrinsic interaction between D-α-tocopherol Succinate (TOS), human serum albumin (HSA) and indocyanine green (ICG). Doxorubicin (DOX) was then loaded due to the ion pairing between DOX and TOS. The feasibility of combined chemo-photothermal therapy induced by DOX-loaded HIT-NPs was carefully evaluated. RESULTS: In vitro, HIT-NPs showed no cytotoxicity on human normal liver cells (HL-7702 cells) but obvious killing effects on murine breast cancer cells (4T1 cells). The combined chemo-photothermal therapeutic effect on 4T1 cells was successfully obtained. DOX-loaded HIT-NPs could effectively accumulate in 4T1 subcutaneous tumors after intravenous injection, and the tumor temperature rapidly increased under laser exposure, indicating the feasibility of PTT in vivo. CONCLUSION: The self-assembled HIT-NPs could provide a promising platform for combined chemo- photothermal cancer therapy with full biocompatibility.
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Neoplasias da Mama , Hipertermia Induzida , Nanopartículas , Albuminas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Humanos , Camundongos , Fototerapia , Terapia Fototérmica , TocoferóisRESUMO
BACKGROUND: Nitrogen (N) is an essential macronutrient that significantly affects turf quality. Commercial cultivars of bermudagrass (Cynodon dactylon (L.) Pers.) require large amounts of nitrogenous fertilizer. Wild bermudagrass germplasm from natural habitats with poor nutrition and diverse N distributions is an important source for low-N-tolerant cultivated bermudagrass breeding. However, the mechanisms underlying the differences in N utilization among wild germplasm resources of bermudagrass are not clear. RESULTS: To clarify the low N tolerance mechanism in wild bermudagrass germplasm, the growth, physiology, metabolome and transcriptome of two wild accessions, C291 (low-N-tolerant) and C716 (low-N-sensitive), were investigated. The results showed that root growth was less inhibited in low-N-tolerant C291 than in low-N-sensitive C716 under low N conditions; the root dry weight, soluble protein content and free amino acid content of C291 did not differ from those of the control, while those of C716 were significantly decreased. Down-regulation of N acquisition, primary N assimilation and amino acid biosynthesis was less pronounced in C291 than in C716 under low N conditions; glycolysis and the tricarboxylic acid (TCA) cycle pathway were also down-regulated, accompanied by a decrease in the biosynthesis of amino acids; strikingly, processes such as translation, biosynthesis of the structural constituent of ribosome, and the expression of individual aminoacyl-tRNA synthetase genes, most of genes associated with ribosomes related to protein synthesis were all up-regulated in C291, but down-regulated in C716. CONCLUSIONS: Overall, low-N-tolerant wild bermudagrass tolerated low N nutrition by reducing N primary assimilation and amino acid biosynthesis, while promoting the root protein synthesis process and thereby maintaining root N status and normal growth.
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Cynodon/genética , Regulação da Expressão Gênica de Plantas , Metaboloma , Nitrogênio/deficiência , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Transcriptoma , Cynodon/metabolismo , Nitrogênio/metabolismo , Melhoramento Vegetal , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Banco de SementesRESUMO
Considering the multiple biological barriers before the entry of photosensitizers (PSs) into cytoplasm, it is of paramount importance to track PSs to elucidate their behaviors and distributions to guide the photodynamic therapy (PDT). Also, the developed PSs suffer from strong oxygen dependency. However, reports on such ideal theranostic platforms are rare. Herein, we developed a theranostic platform (CMTP-2) based on the coumarin-based D-π-A system, which, for the first time, can reveal the holistic intracellular delivery pathway and near-infrared (NIR)-activated mitophagy to guide synergistic type-I PDT and photothermal therapy. The dynamic endo-lysosomal escape of CMTP-2 was monitored, as well as its changeable distributions in endosomes, lysosomes, and mitochondria, demonstrating the preferential accumulation in mitochondria at the end. Upon NIR-I irradiation, CMTP-2 generated toxic radicals and heat, triggering the execution of mitophagy and apoptosis. In vivo experiments on mice indicated that CMTP-2 under 808 nm irradiation realized complete cancer ablation, showing great potential for advancements in synergistic phototherapy.
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Mitofagia , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Lisossomos , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Terapia FototérmicaRESUMO
BACKGROUND: Lacunar infarction (LI) is the mild type in the classification of ischemic stroke, mostly occurs in the middle-aged and elderly, with mild hemiplegia and partial sensory disorder as the main manifestations. In the treatment of LI, acupuncture is often regarded as dominant therapy in the convalescence period. However, acupuncture for treatment of LI in the recovery period lacks high-quality reports and evidence-based medical evidence. Thus, we aim to evaluate the curative effect and safety of acupuncture for LI objectively. METHODS: Pubmed, Cochrane Library, Web of Science, EBSCO, Springer, China National Knowledge Infrastructure, Chinese Scientific and Technical Journals Database (VIP), Wan-fang Database, Chinese Biomedical Literature Database, Chinese Science Citation Database, and other electronic databases will be retrieved from the inception to May, 2021. Randomized controlled trials related to this subject will be searched. The inclusion criteria are established and a detailed literature search strategy is designed through discussion. Article retrieval, screening, excluding repetitive studies, assessment of quality, and data processing will be conducted by 2 reviewers independently using EndNote (X9) and Review Manager (5.3.5). The outcome measures include primary outcome measures (total effective rate, National Institute of Health Stroke Scale score, and Fugl-Meyer Assessment score), secondary outcome measures (blood pressure, plasma glucose, and blood lipid), and safety outcome measures. We will perform a meta-analysis, descriptive analysis, and subgroup analysis based on data conditions. RESULTS: The study of total effective rate, National Institute of Health Stroke Scale score, Fugl-Meyer Assessment score, blood pressure, plasma glucose, blood lipid, and adverse effects will provide evidenced outcome for high-quality synthesis and descriptive analysis. CONCLUSION: This systematic review will kindly provide evidence of whether acupuncture is an effective and safe intervention for LI in the recovery period. INPLASY REGISTRATION NUMBER: INPLASY202150060 (DOI:10.37766/inplasy2021.5.0060).
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Terapia por Acupuntura/efeitos adversos , Hemiplegia/terapia , Distúrbios Somatossensoriais/terapia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral Lacunar/reabilitação , Encéfalo/diagnóstico por imagem , Hemiplegia/etiologia , Humanos , Imageamento por Ressonância Magnética , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios Somatossensoriais/etiologia , Reabilitação do Acidente Vascular Cerebral/efeitos adversos , Acidente Vascular Cerebral Lacunar/complicações , Acidente Vascular Cerebral Lacunar/diagnóstico , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
The production of oxygen by photosynthetic microorganisms (PSMs) has recently attracted interest concerning the in vivo treatment of multiple diseases for their photosynthetic oxygen production in vivo, since PSMs have good biological safety. Here, the first evidence that PSMs can be used as a photothermal source to perform biophotothermal therapy (bio-PTT) is provided. In vitro and in vivo experiments proved that PSMs can generate heat for the direct elimination of tumors and release a series of pathogen-associated molecular patterns and adjuvants for immune stimulation under light irradiation. Bio-PTT enabled a local tumor inhibition rate exceeding 90% and an abscopal tumor inhibition rate exceeding 75%. This strategy also produced a stronger antitumor immune memory effect to prevent tumor recurrence. The bio-PTT strategy provides a novel direction for photothermal therapy as it simultaneously produces local and abscopal antitumor effects.
Assuntos
Hipertermia Induzida , Neoplasias , Linhagem Celular Tumoral , Humanos , Imunidade , Imunoterapia , Neoplasias/terapia , FototerapiaRESUMO
BACKGROUND: COVID-19 has strong transmission power, and people are generally susceptible to it. Patients with weak constitution and low immunity function are more likely to be infected. Aromatic therapy of traditional Chinese medicine has the effect of inhibiting virus and sterilization, especially the external treatment of traditional Chinese medicine has played an important role in the fight against the epidemic situation. METHODS: Nine databases will be searched under the guideline of research strategy, from their inception to March 31, 2021, for relevant randomized controlled trial (RCTs) published. These databases are Cochrane Library, PubMed, EMBASE, Web of Science, ScienceDirect, China National Knowledge Infrastructure, Wan-fang Data, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The types on Language of literature are English and Chinese. Researchers will independently operate the literature research, screening, quality evaluation, data collection, and data analysis with same research strategy and selection criteria. Methodological quality will be evaluated under the guideline of the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be used to determine confidence in the effect estimates. Meta-analysis or subgroup analysis will be performed according to the including data type. Meta-analysis will be performed with Stata 13.0 software. RESULTS: Outcome will be displayed by effective rates, quality of life score, adverse effect. CONCLUSION: This systematic review will provide evidence whether Chinese herbal sachets are effective and safe intervention of COVID-19 Pandemic. REGISTRATION NUMBER IN PROSPERO: CRD42021238580.