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Metal-organic framework nanoparticles (MOF NPs) have received much attention for their potential use in nanopesticides. However, little is known about the potential health and environmental risks associated with these materials. In this study, the toxicological responses of zebrafish exposed to five MOF NPs for short and long periods of time were evaluated. The acute toxicity results showed that the toxicity of the five MOF NPs to zebrafish embryos and adult zebrafish was in the order of Cu-MOF > ZIF-90 > ZIF-8 > Fe-MOF > Zr-MOF. Histopathological analysis revealed that ZIF-8, ZIF-90, and Cu-MOF NPs caused liver swelling and vacuolization in zebrafish. The cellular ultrastructure showed that ZIF-8, ZIF-90, and Cu-MOF NPs severely damaged the mitochondrial structure in intestinal epithelial cells and liver cells. The 16S rDNA sequencing data showed that all five MOF NPs significantly altered the dominant microorganisms in the zebrafish intestine. The microbial markers of intestinal inflammation, Proteobacteria (Aeromonas, Plesiomonas, and Legionella), were significantly increased in the Fe-MOF, ZIF-8, Zr-MOF, and Cu-MOF treatment groups. Metabolomics results indicated that the levels of inflammatory promoting factors (Leukotriene E4, 20-hydroxyeicosatetraenoic acid) in arachidonic acid metabolism were decreased, and the levels of inflammatory suppressing factors (8,9-epoxyeicosatrienoic acid) were increased. Metabolites related to oxidative stress, such as glutamine, pyridoxamine, and l-glutamic acid in vitamin B6 metabolism and other signaling pathways, were significantly reduced. Overall, these results suggest that the different MOF NPs had widely varying toxicity to zebrafish, and further attention should be paid to the toxicity of MOF NPs in the real environment.
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Traumatic brain injury (TBI) presents a significant public health challenge, necessitating innovative interventions for effective treatment. Recent studies have challenged conventional perspectives on neurogenesis, unveiling endogenous repair mechanisms within the adult brain following injury. However, the intricate mechanisms governing post-TBI neurogenesis remain unclear. The microenvironment of an injured brain, characterized by astrogliosis, neuroinflammation, and excessive cell death, significantly influences the fate of newly generated neurons. Adenosine kinase (ADK), the key metabolic regulator of adenosine, emerges as a crucial factor in brain development and cell proliferation after TBI. This study investigates the hypothesis that targeting ADK could enhance brain repair, promote neuronal survival, and facilitate differentiation. In a TBI model induced by controlled cortical impact, C57BL/6 male mice received intraperitoneal injections of the small molecule ADK inhibitor 5-iodotubercidin (ITU) for three days following TBI. To trace the fate of TBI-associated proliferative cells, animals received intraperitoneal injections of BrdU for seven days, beginning immediately after TBI. Our results show that ADK inhibition by ITU improved brain repair 14 days after injury as evidenced by a diminished injury size. Additionally, the number of mature neurons generated after TBI was increased in ITU-treated mice. Remarkably, the TBI-associated pathological events including astrogliosis, neuroinflammation, and cell death were arrested in ITU-treated mice. Finally, ADK inhibition modulated cell death by regulating the PERK signaling pathway. Together, these findings demonstrate a novel therapeutic approach to target multiple pathological mechanisms involved in TBI. This research contributes valuable insights into the intricate molecular mechanisms underlying neurogenesis and gliosis after TBT.
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Background: Prompt coverage of vascular repairs in the extremities is needed to protect from desiccation and trauma. In the absence of local soft tissues to provide early coverage pending demarcation of the tissues and the zone of injury, there is no clear data in the literature on the ideal coverage method. This article is the first to review the use of dermal substitutes for temporary coverage of extremity vascular repairs pending definitive coverage. Methods: We conducted a review of the literature to identify previous articles indexed in PubMed and Ovid using these search terms: [(skin) OR (artificial skin) OR (Integra) OR (dermal substitute) OR (dermal substitute matrix) OR (dermal regeneration) OR (dermal regeneration matrix) OR (dermal regeneration template)] AND [(bypass) OR (graft) OR (vascular surgery) OR (revascularization) OR (salvage) OR (limb salvage) OR (vascular repair) OR (artery repair) OR (arterial repair)] AND [(limb) OR (extremity) OR (leg) OR (arm) OR (vascular injury) OR (amputation)]. Results: Of the 32 articles retrieved for initial review, five case reports with six patients of dermal substitute use for direct coverage of extremity repairs were identified. In all cases, the dermal substitute was able to provide stable coverage pending definitive coverage or was allowed to heal secondarily. Conclusions: Dermal substitute matrices are a potential means of temporary coverage of exposed extremity vascular repairs when there is a paucity of local soft tissues pending more definitive coverage.
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Background: Abdominoplasty techniques are well documented. The ideal position of the umbilicus has, however, received limited attention. Unfortunately, umbilicus position is not universally agreed upon in male cosmetic abdominoplasty. This study was conducted to determine the ideal umbilicus anthropometric measurements in young men, and the relationships between umbilical position and anterior trunk and torso reference points that may be applicable to intraoperative positioning. It is aimed also at investigating whether umbilicus position would be more accurately determined by considering nipple position instead of the abdominal crease, as recently proposed. Methods: Several anthropometric measurements of various anterior abdominal and thoracic landmarks were conducted on 60 young and middle-aged male volunteers and 30 cadavers at São Paulo city. All statistical analysis was completed using Stata software. Results: Of all the measured reference points, a much stronger correlation (0.513) was demonstrated between umbilicus-anterior axillary fold (U-AX) and inter-nipple (N-N) distances with a constant golden number ratio relationship (N-Nâ =â U-AX × 0.618) compared with the weak correlation of 0.034 between umbilicus-xiphisternum and umbilicus-abdominal crease. In 75% of volunteers, the calculated U-AX was within ±3 cm of actual measurement, and in 33.33% within ±1 cm. Conclusions: U-AX = 1.618 × N-N equation is more predictive of adequate umbilicus repositioning during abdominoplasty in male patients. Chest and abdomen of men are a single aesthetic unit. Proper positioning of the nipples and umbilicus, as well as harmonious abdominal and torso proportions are critical for an optimal final aesthetic outcome.
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One of the most important health issues facing the world today is obesity. It is an important independent risk factor for developing type 2 diabetes. Harmine offers various pharmacological effects, such as anti-inflammatory and anti-tumor effects. The current study aims to investigate Harmine's anti-diabetic and anti-adipogenic properties in albino mice after inducing low-grade inflammation with a high-fat diet (HFD). About forty-eight male albino mice were divided into four groups. Group 1: control mice were injected with daily saline and fed a normal chow diet of 21% protein for 5 months. Group 2: mice were treated daily with IP-injected Harmine (30 mg/kg body weight) and were fed a normal chow diet for 5 months. Group 3: mice were fed HFD to induce type 2 Diabetes Mellitus (T2DM) for 5 months. Group 4: mice were fed HFD for 14 weeks and treated with Harmine for the last 6 weeks. A figh-fat diet caused a significant increase in body and organ weight, lipid profiles, and destructive changes within the pancreas, kidney, and liver tissue. The administration of Harmine led to a remarkable improvement in the histological and ultrastructural changes induced by HFD. The findings indicate that mice cured using Harmine had lower oxidative stress, a higher total antioxidant capacity, and a reduced lipid profile compared to HFD mice. Harmine led to the hepatocytes partly restoring their ordinary configuration. Furthermore, it was noticed that the pathological incidence of damage in the structure of both the kidney and pancreas sections reduced in comparison with the diabetic group. Additional research will be required to fully understand Harmine and its preventive effects on the two forms of diabetes.
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Background: Sodium arsenate (Na 3As0 4, Sodium As) is an important toxic substance that leads to nephrotoxicity. Due to having bioactive molecules, such as polyphenols and tyrosol, olive oil plays a significant role in scavenging free radicals. This study aimed to investigate the effects of olive oil and tyrosol on As-induced nephrotoxicity. Methods: In our study, 42 adult male BALB/c mice were randomly divided into six groups: control (normal saline), olive oil (0.4 ml/d, gavage), tyrosol (5 mg/kg/d), Sodium As (15 mg/kg), olive oil + Sodium As, and tyrosol + Sodium As (olive oil and tyrosol received one hour before Sodium As). Drugs were administreted once daily for 30 consecutive days. On the 31st day of the study, oxidative stress parameters in kidney tissue, FRAP in plasma, renal function parameters in serum, and histopathological assays were performed. Results: Sodium As-induced renal damage as characterized by a significant increase of creatinine and BUN (P < 0.001) and histopathological changes. Also, Sodium As markedly altered oxidative stress biomarkers such as a significant increase in MDA (P < 0.001) and significantly decreased in FRAP and GSH (P < 0.01). Olive oil and tyrosol administration significantly improved the renal antioxidant defense system and decreased MDA concentration, markedly preserving the tissue structure and functional markers of kidney. However, these effects were more effective for tyrosol than olive oil. Conclusions: Our results suggest that olive oil and tyrosol can be used as a protective agent in preventing Sodium As-induced nephrotoxicity due to antioxidant property.
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Paediatric complex wounds pose a challenge to the reconstructive surgeon due to the intricacy of reconstructive options required. Developments in microsurgery and microsurgical technique have brought free tissue transfer ever closer to the comfort zone of the reconstructive surgeon for reconstruction of paediatric traumatic complex wounds. We present our experience of microsurgical reconstruction in Lebanon for complex traumatic wounds in paediatric patients under the age of 10 years using the free anterolateral thigh (ALT) flap. The ALT flap has proven its value as a safe, adaptable, and aesthetically acceptable reconstructive option in paediatric complex trauma.
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Colgajo Perforante , Procedimientos de Cirugía Plástica , Humanos , Niño , Colgajo Perforante/cirugía , Muslo/cirugía , Microcirugia/métodos , LíbanoRESUMEN
AIMS: Ehrlich ascites carcinoma and its subcutaneous inoculated solid tumour form (SEC) are reliable models for chemotherapeutic molecular targets exploration. Novel chemotherapeutic approaches are identified as molecular targets for intrinsic apoptosis, like the modulation of the second mitochondria-derived activator of caspases (SMAC). SMAC is a physiological substrate of mitogen-activated protein kinases (MAPKs). Glutathione-S-transferase P1 (GSTP1) and its close association with MAPKs play an important role in malignant cell proliferation, metastasis, and resistance to chemotherapeutics. Nitazoxanide (NTZ) is an emerging cancer therapy and its targeted GSTP1 evidence remains a knowledge need. MAIN METHODS: In the present mice-established SEC, the chemotherapeutic roles of oral NTZ (200 mg/kg/day) and 5-fluorouracil (5-FU; 20 mg/kg/day, intraperitoneally) regimens were evaluated by measuring changes in tumour mass, the tumour MAPKs, cytochrome c, Bcl-2 interacting mediator of cell death (BIM), and SMAC signalling pathway in addition to its molecular downstream; caspases 3 and 9. KEY FINDINGS: Computational analysis for these target protein interactions showed direct-ordered interactions. After individual therapy with NTZ and 5-FU regimens, the histological architecture of the extracted tumour discs revealed decreases in viable tumour regions with significant necrosis surrounds. These findings were consistent with gross tumour sizes. Each separate regimen lowered the remarkable GSTP1 and elevated the low MAPKs expressions, cytochrome c, BIM, SMAC, and caspases 3, and 9 in EST tissues. SIGNIFICANCE: The chemotherapeutic activity of NTZ in SEC was proven. Additionally, NTZ possesses a SMAC modulatory activity that, following thorough research, should be taken into consideration as a chemotherapeutic approach in solid tumours.
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Carcinoma , Caspasas , Animales , Ratones , Caspasas/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Glutatión Transferasa , Citocromos c/metabolismo , Línea Celular Tumoral , Apoptosis , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Mitocondrias/metabolismo , Proteínas Quinasas Activadas por Mitógenos , Biología Computacional , Proteínas Mitocondriales/metabolismoRESUMEN
In this study, pH-responsive LC@O-CMCS/PU nanoparticles were prepared by encapsulating λ-cyhalothrin (LC) with O-carboxymethyl chitosan (O-CMCS) to form LC/O-CMCS and then covering it with polyurethane (PU). Characterization and performance test results demonstrate that LC@O-CMCS/PU had good alkaline release properties and pesticide loading performance. Compared to commercial formulations containing large amounts of emulsifiers (e.g., emulsifiable concentrate, EC), LC@O-CMCS/PU showed better leaf-surface adhesion. On the dried pesticide-applied surfaces, the acute contact toxicity of LC@O-CMCS/PU to Harmonia axyridis (H. axyridis) was nearly 20 times lower than that of LC EC. Due to the slow-releasing property of LC@O-CMCS/PU, only 16.38 % of LC was released at 48 h in dew and effectively reduced the toxicity of dew. On the pesticide-applied leaves with dew, exposure to the LC (EC) caused 86.66 % mortality of H. axyridis larvae significantly higher than the LC@O-CMCS/PU, which was only 16.66 % lethality. Additionally, quantitative analysis demonstrated 11.33 mg/kg of λ-cyhalothrin in the dew on LC@O-CMCS/PU lower than LC (EC) with 4.54 mg/kg. In summary, LC@O-CMCS/PU effectively improves the safety of λ-cyhalothrin to H. axyridis and has great potential to be used in pest control combining natural enemies and chemical pesticides.
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Escarabajos , Plaguicidas , Piretrinas , Animales , Piretrinas/toxicidad , Plaguicidas/toxicidad , Control de Plagas , Concentración de Iones de HidrógenoRESUMEN
A novel series of bioactive water-soluble mononuclear Ru(II)-mixed ligand complexes of 2,2'-bipyridyl and V-shaped Schiff base ligands were synthesized and structurally characterized. Biomedical activities of Ru(II) complexes have been tested in view of antioxidant activities, interaction with calf thymus DNA (CT-DNA), and anticancer performance. The optimized structure of these complexes has been further supported by density functional theory (DFT) calculations. Further, validation of the interaction studies of some complexes was accomplished by carrying out molecular docking studies with DNA using molecular operating environment (MOE) software are reported.Communicated by Ramaswamy H. Sarma.
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Complejos de Coordinación , ADN , Simulación del Acoplamiento Molecular , Ligandos , Teoría Funcional de la Densidad , ADN/química , Complejos de Coordinación/química , Bases de Schiff/químicaRESUMEN
In this work, an enzyme-responsive nanovehicle for improving captan (CAP) contact fungicide bioactivity and translocation in plant tissues was synthesized (CAP-MSNs-ß-glucan) by attaching ß-glucan to the outer surface of mesoporous silica nanoparticles. CAP-MSNs-ß-glucan properties were tested by FTIR, ζ-potential, DLS, XRD, TGA, FE-SEM, and HR-TEM. Cargo protection ability of CAP-MSNs-ß-glucan from photolysis and hydrolysis was examined in comparison to CAP commercial formulation (CAP-CF). CAP-MSNs-ß-glucan distribution in plant tissues, bioactivity against Fusarium graminearum, and biotoxicity toward zebrafish (Danio rerio) were tested and compared with that of CAP-CF. CAP-MSNs-ß-glucan results showed good loading efficacy reaching 18.39% and enzymatic-release dependency up to 83.8% of the total cargo after 20 days of ß-glucan unsealing. CAP-MSNs-ß-glucan showed significant release protection under pH changes. MSNs-ß-glucan showed excellent CAP protection from UV. CAP-MSNs-ß-glucan showed better distribution in corn tissues and 1.28 more inhibiting potency to Fusarium graminearum than CAP-CF. CAP-MSNs-ß-glucan showed 1.88 times lower toxicity than CAP-CF to zebrafish after 96 h of treatment. We recommend using such formulations to overcome shortcomings of contact fungicides and achieve better and sustainable farming.
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PARP inhibitors (PARPi) have modest antitumor activity in patients with advanced breast cancer and mutation in BRCA. It is unclear whether some subgroups derive greater benefit from treatment. MEDLINE and EMBASE were searched from inception to March 2021 to identify trials of PARPi in patients with metastatic breast cancer. Objective response rate (ORR) and clinical benefit rate (CBR) to PARPi were extracted and pooled in a meta-analysis using the Mantel Haenszel random effects model. Meta-regression explored the influence of patient and tumor characteristics on ORR and CBR. For randomized trials, hazard ratio comparing PARPi to control therapy were pooled using inverse variance and random effects. Analysis included 43 studies comprising 2409 patients. Among these, 1798 (75%) patients had BRCA mutations and 1146 (48%) were triple negative. In 10 studies (28%; n = 680 patients), the PARPi was given in combination with platinum-based chemotherapy. Weighted mean ORR was 45%; 64% when combined with platinum vs 37% with PARPi monotherapy (p < 0.001). Previous platinum-based chemotherapy was associated with lower ORR (p = 0.02). Compared to standard chemotherapy, progression-free survival was improved (HR 0.64, p < 0.001), but there was no difference in overall survival (HR 0.87, p = 0.06). There were no differences in ORR or CBR between BRCA1 and BRCA2 mutations. PARPi are more active in combination with platinum than as monotherapy, with lower response if given as monotherapy after platinum exposure. Significant improvements in ORR translated to modest improvement in progression-free, but not overall survival. There was no association between ORR and BRCA mutations.
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Understanding the lethal effects of pesticides nano formulations on the targeted organisms (pathogens) and the non-targeted organisms (fish, earthworms, etc) is essential in assessing the probable impact of new technologies on agriculture and environment. Here we evaluated the bioactivity and the biotoxicity of new type of fungicide smart-delivery formulation based on conjugating carboxymethylated-ß-glucans on the mesoporous silica nanoparticles (MSNs) surface after loading chlorothalonil (CHT) fungicide in the MSNs pores. The obtained formulation has been characterized with FE-SEM, and HR-TEM. The CHT loading efficiency has been measured with TGA. The bioactivity of the obtained formulation (CHT@MSNs-ß-glucans) has been tested against four pathogens, fusarium head blight (Fusarium graminearum), sheath rot (Sarocladium oryzae), rice sheath blight (Rhizoctonia solani), and soyabean anthracnose (Colletotrichum truncatum) compared with CHT WP 75% commercial formulation (CHT-WP) and technical CHT. The environmental biotoxicity of CHT@MSNs-ß-glucans compared with CHT-WP has been tested toward earthworm (Eisenia fetida) and zebra fish (Danio rerio). The results showed that CHT@MSNs-ß-glucans has an excellent bioactivity against the subjected pathogens with better inhabiting effects than CHT-WP. CHT@MSNs-ß-glucans toxicity to Eisenia fetida was found 2.25 times lower than CHT-WP toxicity. The LC50 of CHT@MSNs-ß-glucans to zebra fish after the first 24h was 2.93 times higher than CHT-WP. After 96h of treatment, the LC50 of CHT@MSNs-ß-glucans was 2.66 times higher than CHT-WP. This work highlighted the necessity to increase the mandatory bioassays of nano formulations with the major non-target organisms in the environmental risk assessment of new pesticide formulations.
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Fungicidas Industriales , Nanopartículas , beta-Glucanos , Animales , Colletotrichum , Portadores de Fármacos , Fungicidas Industriales/toxicidad , Fusarium , Hypocreales , Nanopartículas/toxicidad , Nitrilos , Porosidad , Rhizoctonia , Dióxido de Silicio/toxicidad , beta-Glucanos/toxicidadRESUMEN
Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.
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The present study examines the impacts of supplementing yogurt with 1% whey protein concentrate (WPC), Ca-caseinate (Ca-CN) and Spirulina platensis on the physiological performance of V-line rabbits receiving diets containing yogurt (at a dose of 5 g/kg body weight/day) and the different meat quality aspects. The results show that fat content was highest (p < 0.05) in yogurt fortified with Spirulina powder, but protein (%) was highest in yogurt enriched with WPC. Yogurt containing Spirulina powder showed a significant (p < 0.05) increase in total antioxidant activity. The final live body weight for G1 was higher than the other groups. However, additives affected the saddle, hind legs, liver and neck percentages significantly (p < 0.05). There were not significant differences for all groups in the forelegs, lung and heart percentages. LDL-cholesterol, total protein, globulin, albumin, creatinine and immunoglobulin M values were lowest (p < 0.05) in the WPC group. Significant improvements appeared in the small intestinal wall, microbiology, growth performance, serum biochemistry, organ histology and meat quality of the group receiving enriched yogurt. Yogurts enriched with WPC, Ca-CN and Spirulina platensis can be used as functional foods.
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Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.
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Antineoplásicos/farmacología , Hidrocarburos Aromáticos con Puentes/farmacología , Diseño de Fármacos , Inhibidores de Proteínas Quinasas/farmacología , Tiazoles/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proteínas Quinasas/metabolismo , Tiazoles/síntesis química , Tiazoles/química , Células Tumorales CultivadasRESUMEN
In this study, a pesticide controlled release system with dual response characteristics of pH and enzyme triggering was developed. Indoxacarb (IDC) was loaded into hollow mesoporous silica (HMS) nanoparticles, carboxylated ß-cyclodextrin (ß-CD) acted as a capping molecule to couple with the amino-functionalized HMS, and their well-defined morphological structures were confirmed by scanning electron microscopy and transmission electron microscopy. The results showed that the prepared IDC loaded HMS-CD had high loading efficiency (26.42%, w/w) and showed excellent dual response properties to pH and the α-amylase enzyme. IDC loaded HMS-CD nanoparticles showed better insecticidal activity against Spodoptera frugiperda than applying the same dose of IDC emulsifiable concentrate, and the toxicity of IDC loaded HMS-CD to zebrafish was reduced by more than 5-fold, indicating that insecticide delivery systems based on ß-CD-anchored HMS nanoparticles could potentially be applied for sustainable control of pests and reduce harm to non-target organisms and the environment.
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Portadores de Fármacos/química , Insecticidas/farmacología , Nanopartículas/química , Oxazinas/farmacología , Dióxido de Silicio/química , beta-Ciclodextrinas/química , Animales , Portadores de Fármacos/toxicidad , Nanopartículas/toxicidad , Porosidad , Dióxido de Silicio/toxicidad , Spodoptera/efectos de los fármacos , Pez Cebra , beta-Ciclodextrinas/toxicidadRESUMEN
BACKGROUND: Pediatric sarcomas are the most common malignancies of bones in childhood. With advances in adjuvant treatment, limb salvage surgery has become common, increasing the demand of skeletal reconstruction. Traditional practice included bone grafting and transport. Recently, microsurgical tissue transfer in pediatric patients has become a well-accepted practice, with the fibula as an ideal biologic construct for long bone reconstruction. We aim to assess the success rate of this operation, including flap survival, bony union, weight-bearing ambulation, and complications. METHODS: We identified 10 pediatric patients who underwent reconstruction of long bones (femur, humerus, or tibia) with a free fibula flap from January 2015 to January 2020. All patients received neoadjuvant chemotherapy 4 weeks prior to the surgical procedure followed by adjuvant chemotherapy. RESULTS: The average follow-up time was 15 months. We had no partial or total flap loss. Three of our patients passed away in the first post-operative year due to metastatic disease. In the remaining 7 patients, we had two long-term complications. The fibula of one patient did not exhibit hypertrophy, yet weight-bearing ambulation was achieved. The other patient had nonunion proximally that required bone grafting at 8 months post-operatively. After that, the same patient fractured her fibula and required surgical fixation. She was eventually able to achieve weight-bearing ambulation. CONCLUSION: The vascularized fibula flap is a reliable tool for reconstruction in children. Flap survival is similar to that of adults. Complication rate is low compared to that for other forms of reconstruction.
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Neoplasias Óseas , Peroné/trasplante , Colgajos Tisulares Libres , Efectos Adversos a Largo Plazo , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Sarcoma de Ewing , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Trasplante Óseo/efectos adversos , Trasplante Óseo/métodos , Niño , Extremidades/patología , Extremidades/cirugía , Femenino , Colgajos Tisulares Libres/efectos adversos , Colgajos Tisulares Libres/trasplante , Humanos , Líbano/epidemiología , Recuperación del Miembro/métodos , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/epidemiología , Efectos Adversos a Largo Plazo/etiología , Masculino , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/cirugía , Evaluación de Procesos y Resultados en Atención de Salud , Pediatría/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/patología , Sarcoma de Ewing/cirugíaRESUMEN
DNA methylation has a major role in cancer, and its inhibitors are used therapeutically. DNA methylation depends on methyl group flux through the transmethylation pathway, which forms adenosine. We hypothesized that an adenosine kinase isoform with nuclear expression (ADK-L) determines global DNA methylation in cancer cells. We quantified ADK-L expression (Western Blot) and global DNA methylation as percent 5-methyldeoxycytidine (5mdC, LC-MS/MS) in three cancer lines (HeLa, HepG2, and U373). ADK-L expression and global DNA methylation correlated positively with the highest levels in HeLa cells compared to U373 and HepG2 cells. To determine whether ADK increases global DNA methylation and to validate its potential therapeutics, we treated HeLa cells with potent ADK inhibitors MRS4203 and MRS4380 (IC50 88 and 140 nM, respectively). Both nucleosides, but not a structurally related poor ADK inhibitor, significantly reduced global DNA methylation in HeLa cells in a concentration-dependent manner. Thus, ADK-L is a potential target for the therapeutic manipulation of DNA methylation levels in cancer.
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BACKGROUND: Water hyacinth (Eichhornia crassipes) is considered the most damaging aquatic weed in many countries. Chemical methods are still the primary approach to control, although this directly exposes the natural enemy of water hyacinth (water hyacinth weevil) to herbicides. In addition, spray drift can easily damage non-target plants. In this study, herbicides, natural polymer materials (chitosan and carboxymethyl chitosan), sodium alginate and natural oils (citronella oil) were used to prepare novel floating polysaccharide granules as a solution for controlling water hyacinth. RESULTS: 2-Methyl-4-chlorophenoxy acetic acid (MCPA) floating granules with a spherical structure were prepared using a MCPA-chitosan-sodium alginate-oil cross-linking and embedding method. The granules produced showed the required properties of floatation and slow controlled herbicide release. In addition, the polysaccharide granules collected around water hyacinth plants and enabled targeted release of the active herbicide ingredients onto the stems and roots of the weed, thereby stopping the herbicide from reaching non-target plants and preventing regrowth of water hyacinth. CONCLUSION: We successfully prepared highly effective MCPA-loaded floating granules, which compared with an MCPA solution, exerted greater control on water hyacinth. Concomitantly, these granules provide a solution to spray drift and ensure the safety of natural enemies of water hyacinth, which is of great significance in research on herbicide formulations.