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This study aimed to develop a nanostructured lipid carrier (NLC) capable of co-delivering paclitaxel (PTX) and programmed death-ligand 1 (PD-L1) small interfering RNA (siRNA) to enhance PTX bioavailability and bolster immunity through PD-L1 knockdown. We prepared a PTX-loaded NLC (P-NLC) and coated it with positively charged chitosan (Chi) to create P-NLC-Chi, which was subsequently conjugated to siRNA (P-NLC-Chi-siRNA). The P-NLC-Chi formulation was optimized using the Box-Behnken design. P-NLC-Chi measured 123.8 ± 0.52 nm (zeta potential, 22.71 ± 0.49 mV). By verifying the gel retardation assay and observing changes in the zeta potential, the optimal binding ratio of NLC to PD-L1 siRNA was identified as 50:1. The P-NLC-Chi-siRNA particle size was 181.97 ± 0.67 nm, with a zeta potential of 18.66 ± 0.23 mV. siRNA stability was observed in serum over a 24-h period. Enhanced cytotoxicity and intracellular uptake of the complex were evident in breast cancer cells and breast cancer-resistant cells (MCF-7 and MCF-7/ADR cells, respectively). Evaluation of P-glycoprotein-mediated efflux demonstrated that NLC mitigated drug efflux in MCF-7/ADR cells. Subcutaneous injection of P-NLC-Chi-siRNA into tumor-bearing BALB/c nude mice injected with MCF-7/ADR cells revealed a reduction in tumor size. In vitro and in vivo experiments indicated a significant reduction in PD-L1 mRNA expression levels. Additionally, an in vivo study revealed tumor-specific CD4 + and CD8 + T cell responses within the tumor tissue following the injection of P-NLC-Chi-siRNA. Our findings suggest that Chi-coated NLC for the co-delivery of PTX and PD-L1 siRNA has great potential as an innovative delivery system for chemoimmunotherapy.
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This study focused on the physicochemical properties and tenderness of vacuum-packaged beef M. semitendinosus as affected by various dilution ratios (DRs, 1:4, 1:2, and 1:1) of green kiwifruit juice extract (GKJE) with phosphate buffer during storage at 4°C for 7 days. In addition, the formation of peptides with antioxidant activity for GKJE ability to hydrolyze proteins present in beef was evaluated at different steps of in vitro digestion. Beef with GKJE showed higher tenderness than control (CTL, beef with brine solution alone) during storage, and the increased DR increased tenderness as compared to lower DRs. The addition of GKJE increased protein digestibility during in vitro digestion. To increase the antioxidant activity in the body, GKJE having a DR of 1:2 and 1:1 should be applied to the beef muscle with effective antioxidant activity. These results suggest that DRs of phosphate buffer and kiwifruit juice of 1:1 and 1:2 have the potential to be used as a meat-tenderizing agent and could increase the digestibility of meat as well as the antioxidant capability of bioactive peptides. PRACTICAL APPLICATION: The dilution ratio of kiwi juice with phosphate buffer at 1:1 has the potential to be used as a meat-tenderizing agent during refrigerated storage and also increase the digestibility of beef.
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Actinidia , Antioxidantes , Digestão , Sucos de Frutas e Vegetais , Extratos Vegetais , Carne Vermelha , Antioxidantes/análise , Bovinos , Actinidia/química , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sucos de Frutas e Vegetais/análise , Carne Vermelha/análise , Photinia/química , Músculo Esquelético/química , Frutas/química , Armazenamento de Alimentos/métodosRESUMO
Wide-bandgap perovskite solar cells (PSCs) with high open-circuit voltage (Voc) represent a compelling and emerging technological advancement in high-performing perovskite-based tandem solar cells. Interfacial engineering is an effective strategy to enhance Voc in PSCs by tailoring the energy level alignments between the constituent layers. Herein, n-type quinoxaline-phosphine oxide-based small molecules with strong dipole moments is designed and introduce them as effective cathode interfacial layers. Their strong dipole effect leads to appropriate energy level alignment by tuning the work function of the Ag electrode to form an ohmic contact and enhance the built-in potential within the device, thereby improving charge-carrier transport and mitigating charge recombination. The organic interfacial layer-modified wide-bandgap PSCs exhibit a high Voc of 1.31 V (deficit of <0.44 V) and a power conversion efficiency (PCE) of 20.3%, significantly improved from the device without an interface dipole layer (Voc of 1.26 V and PCE of 16.7%). Furthermore, the hydrophobic characteristics of the small molecules contribute to improved device stability, retaining 95% of the initial PCE after 500 h in ambient air.
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The pogo transposable element derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple negative breast cancers (TNBC). In well-characterized models of TNBC, POGZ exerted a dual role, both as a tumor promoter and metastasis suppressor. Mechanistically, loss of POGZ potentiated TGFß pathway activation to exert cytostatic effects while simultaneously increasing the mesenchymal and migratory properties of breast tumors. Whereas POGZ levels are elevated in human breast cancers, the most aggressive forms of TNBC tumors, including those with increased mesenchymal and metastatic properties, exhibit dampened POGZ levels, and low POGZ expression was associated with inferior clinical outcomes in these tumor types. Taken together, these data suggest that POGZ is a critical suppressor of the early stages of the metastatic cascade.
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OBJECTIVE: Although pork loins is not a tough meat, they need to develop meat products with a soft texture for the elderly. This study focused on the physicochemical properties and tenderness characteristics of pork loin injected with green kiwifruit juice (GRJ) and gold kiwifruit juice (GOJ) during various incubation times. In addition, the antioxidant activities of hydrolysate derived from the hydrolysis of pork loin by kiwifruit juice protease were evaluated. METHODS: The pork loin was injected with 10% and 20% GRJ and GOJ, under various incubation times (0, 4, 8, and 24 h). Then, the physicochemical properties and tenderness of pork loins were measured. 2,2- diphenyl-1-picrylhydrazyl radical scavenging activity and reducing power were conducted to determine hydrolysate's antioxidant activities derived from pork loin's hydrolysis by kiwifruit juice protease. RESULTS: GRJ had greater tenderizing ability than GOJ, even at the 10% addition. When kiwifruit juice was injected into pork loin, the tenderness increased with increasing incubation time. This was confirmed by the decrease in intensity of the myosin heavy chain (MHC) band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In particular, the MHC band decreased at 8 h for both 10% GRJ and 20% GOJ and at 4 h for 20% GRJ alone. The highest myofibril fragmentation index and peptide solubility were observed in pork loin treated with 20% GRJ compared to the other treatments during incubation. The 10% GRJ and 20% GOJ treatments showed similar levels of antioxidant activity of the protein hydrolysates in pork loin, and 20% GRJ showed the highest activity among the treatments. CONCLUSION: Kiwifruit juice had protease activity, and GRJ was more useful for tenderizing meat products than GOJ. Thus, GRJ at 10% could be a potential agent to tenderize and enrich the natural antioxidant activity through the proteolysis of pork loin.
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Antibacterial films have gained attention since the outbreak of the COVID-19 pandemic; however, the impact of metals contained in antibacterial films on human safety have not been sufficiently investigated. This study reports on the important features that must be considered when assessing the bioaccessibility of Ag, Cu, and Zn in antibacterial films. Specifically, the effects of the artificial sweat component (i.e., amino acid and pH), surface weathering of antibacterial films, wipe sampling, and sebum were carefully examined. Our findings suggest that amino acids greatly affect bioaccessibility as amino acids act as ligands to facilitate metal ion leaching. In addition, constant exposure to ultraviolet C causes the film surface to oxidize, which significantly increases metal bioaccessibility due to the electrostatic repulsion between metal oxides and organic substrates. The presence of sebum in artificial sweat and physical damage to the film surface had no significant effects. Furthermore, the wipe sampling used to mimic the realistic dermal contact suggests the feasibility of applying this method for the assessment of bioaccessibility of metals in antibacterial films. The method offers significant advantages for evaluating the human safety aspects of skin contact with consumer products in future research.
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Metais Pesados , Pandemias , Humanos , Metais/análise , Pele/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Aminoácidos/metabolismo , Metais Pesados/análise , Monitoramento Ambiental/métodosRESUMO
Emerging data suggest a significant cross-talk between metabolic and epigenetic programs. However, the relationship between the mechanistic target of rapamycin (mTOR), which is a pivotal metabolic regulator, and epigenetic modifications remains poorly understood. Our results show that mTORC1 activation caused by the abrogation of its negative regulator tuberous sclerosis complex 2 (TSC2) coincides with increased levels of the histone modification H3K27me3 but not H3K4me3 or H3K9me3. This selective H3K27me3 induction was mediated via 4E-BP-dependent increase in EZH2 protein levels. Surprisingly, mTOR inhibition also selectively induced H3K27me3. This was independent of TSC2, and was paralleled by reduced EZH2 and increased EZH1 protein levels. Notably, the ability of mTOR inhibitors to induce H3K27me3 levels was positively correlated with their anti-proliferative effects. Collectively, our findings demonstrate that both activation and inhibition of mTOR selectively increase H3K27me3 by distinct mechanisms, whereby the induction of H3K27me3 may potentiate the anti-proliferative effects of mTOR inhibitors.
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We explored blockchain's applications in nursing informatics, highlighting its potential to improve patient care and data management. We compared and analyzed eight studies focusing on blockchain in Electronic Health Records (EHR) management, nursing optimization, and research facilitation. Although most of these studies are in the proposal stage, blockchain's technical features show promise in enhancing nursing practices and supporting nursing informatics researchers with the integration of technologies.
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Background: Cancer cachexia-characterized by anorexia, body weight loss, skeletal muscle atrophy, and fat loss-affects nearly 80% of cancer patients and accounts for 20% of cancer deaths. Curcuma xanthorrhiza, known as Java turmeric, and its active compound xanthorrhizol (XAN) exhibit anticancer, anti-inflammatory, and antioxidant properties. However, the ameliorative effects of C. xanthorrhiza extract (CXE) and XAN on cancer-associated adipose atrophy remain unexplored. This study aimed to evaluate the therapeutic effects of CXE and XAN on cancer cachexia-induced adipose tissue wasting in CT26 tumor-bearing mice. Methods: CT26 cells were injected subcutaneously into the right flank of BALB/c mice to establish a cancer cachexia model. To evaluate the inhibitory effects of CXE and XAN on cancer cachexia, 50 and 100 mg/kg CXE and 15 mg/kg XAN were administered orally every day for 1 week. Results: CXE and XAN administration significantly attenuated the loss of body weight and epidydimal fat mass by cancer cachexia. In epididymal adipose tissues, administration of CXE or XAN inhibited white adipose tissue browning by repressing expression of the thermogenic genes. Simultaneously, CXE or XAN attenuated fat catabolism through the downregulation of lipolytic genes. The administration of CXE or XAN induced the expression of genes associated with adipogenesis and lipogenesis-related genes. Moreover, CXE or XAN treatment was associated with maintaining metabolic homeostasis; regulating the expression of adipokines and AMP-activated protein kinase (AMPK). Conclusions: CXE and XAN mitigate cancer-induced adipose tissue atrophy, primarily by modulating lipid metabolism and WAT browning, indicating their therapeutic potential for cachectic cancer patients.
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Synthetic oligonucleotides have become a fundamental tool in a wide range of biological fields, including synthetic biology, biosensing, and DNA storage. Reliable access to equipment for synthesizing high-density oligonucleotides in the laboratory ensures research security and the freedom of research expansion. In this study, we introduced the Open-Source Inkjet DNA Synthesizer (OpenIDS), an open-source inkjet-based microarray synthesizer that offers ease of construction, rapid deployment, and flexible scalability. Utilizing 3D printing, Arduino, and Raspberry Pi, this newly designed synthesizer achieved robust stability with an industrial inkjet printhead. OpenIDS maintains low production costs and is therefore suitable for self-fabrication and optimization in academic laboratories. Moreover, even non-experts can create and control the synthesizer with a high degree of freedom for structural modifications. Users can easily add printheads or alter the design of the microarray substrate according to their research needs. To validate its performance, we synthesized oligonucleotides on 144 spots on a 15 × 25-mm silicon wafer filled with controlled pore glass. The synthesized oligonucleotides were analyzed using urea polyacrylamide gel electrophoresis.
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DNA , Oligonucleotídeos , DNA/química , Análise em MicrossériesRESUMO
OBJECTIVE: The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD. METHODS: Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome. RESULTS: Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017). CONCLUSIONS: In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.
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Adenocarcinoma , Mielite Transversa , Neuromielite Óptica , Humanos , Neuromielite Óptica/complicações , Neuromielite Óptica/epidemiologia , Aquaporina 4 , Autoanticorpos , Adenocarcinoma/complicações , Adenocarcinoma/epidemiologia , Imunoglobulina GRESUMO
Humans, especially infants, are exposed to harmful substances through various means, including non-nutritive sucking behaviors. Here, we compared the "one-compartment model" and the "three-compartment model" within the "suck model" to assess the oral bioaccessibility of heavy metals in various products and evaluated whether these models can be employed to assess 12 heavy metals present in consumer products. Several certified reference materials, including plastic, paint, glass, and metals, were employed to ensure sample homogeneity. By comparing the two models, we validated that a considerable amount of complexes were formed between saliva components and the extracted heavy metals and that some of these complexes dissociated during reactions with the gastric/intestinal fluids. Furthermore, we observed that in the cases of Cu and Pb, additional complexes were formed as a result of reactions with gastric/intestinal fluids. We measured the total concentrations of the extracted heavy metals using artificial saliva through acid digestion and found that up to 99.7% of the heavy metals participated in the formation of complexes, depending on the characteristics of the sample (e.g., composition) and the target element. This result indicates that the current suck model may notably underestimate the oral bioaccessibility of heavy metals in products associated with sucking behaviors. Therefore, we propose a more conservative and simpler test method for assessing oral bioaccessibility of heavy metals that involves measuring the total concentrations of heavy metals extracted from consumer products using artificial saliva. By doing so, we can account for potential variations in the digestive milieu (e.g., due to ingested food) and the inconsistency in complex formation-dissociation characteristics.
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Metaloides , Metais Pesados , Poluentes do Solo , Lactente , Humanos , Saliva Artificial , Metais Pesados/análise , Digestão , Hábitos , Monitoramento Ambiental/métodos , Medição de Risco/métodos , Poluentes do Solo/análiseRESUMO
Invasive pulmonary aspergillosis (IPA) can occur in immunocompromised patients, and an early detection and intensive treatment are crucial. We sought to determine the potential of Aspergillus galactomannan antigen titer (AGT) in serum and bronchoalveolar lavage fluid (BALF) and serum titers of beta-D-glucan (BDG) to predict IPA in lung transplantation recipients, as opposed to pneumonia unrelated to IPA. We retrospectively reviewed the medical records of 192 lung transplant recipients. Overall, 26 recipients had been diagnosed with proven IPA, 40 recipients with probable IPA, and 75 recipients with pneumonia unrelated to IPA. We analyzed AGT levels in IPA and non-IPA pneumonia patients and used ROC curves to determine the diagnostic cutoff value. The Serum AGT cutoff value was 0.560 (index level), with a sensitivity of 50%, specificity of 91%, and AUC of 0.724, and the BALF AGT cutoff value was 0.600, with a sensitivity of 85%, specificity of 85%, and AUC of 0.895. Revised EORTC suggests a diagnostic cutoff value of 1.0 in both serum and BALF AGT when IPA is highly suspicious. In our group, serum AGT of 1.0 showed a sensitivity of 27% and a specificity of 97%, and BALF AGT of 1.0 showed a sensitivity of 60% and a specificity of 95%. The result suggested that a lower cutoff could be beneficial in the lung transplant group. In multivariable analysis, serum and BALF AGT, with a minimal correlation between the two, showed a correlation with a history of diabetes mellitus.
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Pathogen effectors can suppress various plant immune responses, suggesting that they have multiple targets in the host. To understand the mechanisms underlying plasma membrane-associated and effector-mediated immunity, we screened the Phytophthora capsici RxLR cell death-inducer suppressing immune system (CRISIS). We found that the cell death induced by the CRISIS2 effector in Nicotiana benthamiana was inhibited by the irreversible plasma membrane H+-ATPase (PMA) activator fusicoccin. Biochemical and gene-silencing analyses revealed that CRISIS2 physically and functionally associated with PMAs and induced host cell death independent of immune receptors. CRISIS2 induced apoplastic alkalization by suppressing PMA activity via its association with the C-terminal regulatory domain. In planta expression of CRISIS2 significantly enhanced the virulence of P. capsici, whereas host-induced gene-silencing of CRISIS2 compromised the disease symptoms and the biomass of the pathogen. Thus, our study has identified a novel RxLR effector that plays multiple roles in the suppression of plant defense and in the induction of cell death to support the pathogen hemibiotrophic life cycle in the host plant.
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Phytophthora infestans , Morte Celular , Virulência , Nicotiana/genética , Membrana Celular , Adenosina Trifosfatases , Doenças das Plantas , Imunidade Vegetal/fisiologiaRESUMO
Ticagrelor (TCG), an antiplatelet agent, has low solubility and permeability; thus, there are many trials to apply the pharmaceutical technology for the enhancement of TCG solubility and permeability. Herein, we have developed the TCG high-loaded nanostructured lipid carrier (HL-NLC) and solidified the HL-NLC to develop the oral tablet. The HL-NLC was successfully fabricated and optimized with a particle size of 164.5 nm, a PDI of 0.199, an encapsulation efficiency of 98.5%, and a drug loading of 16.4%. For the solidification of HL-NLC (S-HL-NLC), the adsorbent was determined based on the physical properties of the S-HL-NLC, such as bulk density, tap density, angle of repose, Hausner ratio, Carr's index, and drug content. Florite R was chosen because of its excellent adsorption capacity, excellent physical properties, and solubility of the powder after manufacturing. Using an S-HL-NLC, the S-HL-NLC tablet with HPMC 4 K was prepared, which is showed a released extent of more than 90% at 24 h. Thus, we have developed the sustained release tablet containing the TCG-loaded HL-NLC. Moreover, the formulations have exhibited no cytotoxicity against Caco-2 cells and improved the cellular uptake of TCG. In pharmacokinetic study, compared with raw TCG, the bioavailability of HL-NLC and S-HL-NLC was increased by 293% and 323%, respectively. In conclusion, we successfully developed the TCG high-loaded NLC tablet, that exhibited a sustained release profile and enhanced oral bioavailability.
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Sistemas de Liberação de Medicamentos , Nanoestruturas , Humanos , Portadores de Fármacos/farmacocinética , Ticagrelor , Preparações de Ação Retardada , Células CACO-2 , Comprimidos , Lipídeos , Tamanho da PartículaRESUMO
OBJECTIVE: The current study aimed to investigate the sociodemographic and psychological variables as well as the function of NSSI related to the cessation of NSSI by analyzing the difference between those currently engaged in nonsuicidal self-injury (NSSI) and those who have stopped NSSI behaviors. METHODS: A total of 490 adults with a history of NSSI (359 females) were assigned to one of two groups: NSSI engagement within the last 12 months or "current NSSI" (n = 402) vs. no episode of NSSI in the previous 12 months or "lifetime NSSI" (n = 88). RESULTS: There were no significant group differences in sex or socioeconomic status, while individuals with current NSSI were slightly younger than those who had ceased NSSI behavior. Regarding the functions of NSSI, the current NSSI group endorsed more intrapersonal functions. Moreover, the participants who had ceased NSSI behavior reported significantly less perceived stress, dysfunctional attitudes, alexithymia, emotion reactivity, and suicidal ideation. On the other hand, the lifetime NSSI group showed greater psychological resources such as self-esteem, distress tolerance, and resilience. CONCLUSIONS: We revealed apparent differences in NSSI functions, clinical symptoms, and psychological resources depending on the maintenance and cessation of NSSI. This study highlights the need for a better understanding of the factors that stop as well as those that continue NSSI behaviors. HIGHLIGHTSThe lifetime NSSI group reported less intrapersonal NSSI functions.The current NSSI group suffered from more clinical symptoms.Individuals who ceased NSSI had more psychological resources.
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Comportamento Autodestrutivo , Adulto , Feminino , Humanos , Comportamento Autodestrutivo/psicologia , Ideação Suicida , Ansiedade , Comportamentos Relacionados com a Saúde , Sintomas Afetivos , Fatores de RiscoRESUMO
The prevalence of women with a raised body mass index (BMI) seeking assisted conception treatment is increasing. Findings of existing studies evaluating the effect of female BMI on intrauterine insemination (IUI) treatment outcomes remain inconsistent. This systematic review and meta-analysis evaluate the effect of female BMI on IUI treatment outcomes. Two authors independently conducted data extraction and assessed study quality. Risk ratios (RR) and 95% confidence intervals were calculated using the Mantel-Haenszel approach for dichotomous outcomes. 11 studies involving 23,145 IUI treatment events, comprising 21,211 cycles from 8 studies, and 1,934 participants in three studies, met the inclusion criteria for the meta-analysis. Two cohorts of women undergoing IUI treatment were compared - women with normal BMI < 25 kg/m2 were compared with a second cohort of women with a BMI category ≥ 25 kg/m2. There was no statistically significant difference in live birth rate (LBR) (RR 1.06, 95% CI 0.86-1.307); clinical pregnancy rate (CPR) (RR 0.94, 95% CI 0.78-1.13); miscarriage (RR 0.92, 95% CI 0.31-2.74) or ectopic pregnancy rate (RR 2.20, 95% CI 0.78-6.23). Our meta-analysis showed that a raised female BMI did not affect IUI treatment outcomes. Nevertheless, weight loss counselling should be offered to women with a raised BMI undergoing IUI, to reduce the associated obstetric morbidity.
A meta-analysis of 11 studies found that having a raised female BMI did not change IUI treatment outcomes.
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Aborto Espontâneo , Fertilização in vitro , Gravidez , Feminino , Humanos , Índice de Massa Corporal , Fertilização , InseminaçãoRESUMO
Zaltoprofen is a nonsteroidal anti-inflammatory drug with poor oral bioavailability. S(+)-zaltoprofen (SZPF)-loaded nanostructured lipid carriers (NLCs) were prepared to enhance oral bioavailability. SZPF-loaded NLCs (NLC-SZPF) were prepared using the hot-melting homogenization method and optimized using the Box-Behnken design. The characterization of optimized NLC-SZPF, in vitro release, cytotoxicity, cellular uptake, ex vivo permeability, and pharmacokinetic parameters were evaluated to confirm the advantages of NLC formulation. NLC-SZPF with a diameter of 105.5 ± 1.2 nm had a high encapsulation efficiency of 99.84 ± 0.01%. NLC-SZPF showed a sustained-release profile, high biocompatibility, and high permeability across the intestinal tract. The relative bioavailability of NLC-SZPF was 431.3% compared with that of SZPF after oral administration to experimental rats. NLC-SZPF was successfully optimized using experimental designs to enhance the oral bioavailability of SZPF. Hence, NLC-SZPF could be a promising approach to overcome the poor oral bioavailability of SZPF.
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Portadores de Fármacos , Nanoestruturas , Ratos , Animais , Disponibilidade Biológica , Lipídeos , Solubilidade , Tamanho da Partícula , Administração Oral , ExcipientesRESUMO
The bZIP gene family is one of the largest transcription factor families and has important roles in plant growth, development, and stress responses. However, bZIP genes in the Solanaceae family have not been extensively investigated. Here, we conducted genome-wide re-annotation in nine Solanaceae species and Arabidopsis thaliana. We annotated 935 bZIP genes, including 107 (11%) that were newly identified. Structural analyses of bZIP genes in the Solanaceae family revealed that the bZIP domain displayed two types of architectures depending on the presence of an additional domain, suggesting that these architectures generate diversified structures and functions. Motif analyses indicated that the two types of bZIP genes had distinct sequences adjacent to the bZIP domain. Phylogenetic analyses suggested that the two types of bZIP genes distinctly evolved and ultimately adapted in different lineages. Transcriptome analyses in pepper (Capsicum annuum) and tomato (Solanum lycopersicum) revealed putative functional diversity between the two types of bZIP genes in response to various abiotic stresses. This study extensively updated bZIP gene family annotations and provided novel evolutionary and functional evidence for the role of bZIP genes in Solanaceae plants. Our findings provide evolutionary and functional characteristics of bZIP genes for a better understanding of their roles in Solanaceae plants.
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Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.