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1.
Small Methods ; 8(2): e2300417, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37330645

RESUMO

Gas sensors are of great interest to portable and miniaturized sensing technologies with applications ranging from air quality monitoring to explosive detection and medical diagnostics, but the existing chemiresistive NO2 sensors still suffer from issues such as poor sensitivity, high operating temperature, and slow recovery. Herein, a high-performance NO2 sensors based on all-inorganic perovskite nanocrystals (PNCs) is reported, achieving room temperature operation with ultra-fast response and recovery time. After tailoring the halide composition, superior sensitivity of ≈67 at 8 ppm NO2 is obtained in CsPbI2 Br PNC sensors with a detection level down to 2 ppb, which outperforms other nanomaterial-based NO2 sensors. Furthermore, the remarkable optoelectronic properties of such PNCs enable dual-mode operation, i.e., chemiresistive and chemioptical sensing, presenting a new and versatile platform for advancing high-performance, point-of-care NO2 detection technologies.

2.
Front Cardiovasc Med ; 10: 1266549, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028488

RESUMO

Objective: Patients with connective tissue disease have a poor prognosis after receiving cardiac surgery. This study described the clinical scenarios and investigated factors correlated with acute kidney injury (AKI) after on-pump cardiac surgery in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods: Patients with SLE or vasculitis who underwent on-pump cardiac surgery from March 2002 to March 2022 were enrolled, while patients with preoperative renal dysfunction were excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Uni- and multivariable analyses were performed to identify potential factors associated with postoperative AKI. Results: Among 123 patients enrolled, 39 (31.7%) developed AKI within seven days after receiving on-pump cardiac surgery. Four patients died in the hospital, resulting in an overall in-hospital mortality of 3.3%, and all deaths occurred in the AKI group. Patients in the AKI group also had longer ICU stays (median difference 3.0 day, 95% CI: 1.0-4.0, P < 0.001) and extubation time (median difference 1.0 days, 95% CI: 0-2.0, P < 0.001) than those in the non-AKI group. Multivariable logistic regression revealed that BMI over 24 kg/m2 (OR: 3.00, 95% CI: 1.24-7.28) and comorbid SLE (OR: 4.73, 95% CI: 1.73-12.93) were independently correlated with postoperative AKI. Conclusion: Factors potentially correlated with AKI following on-pump cardiac surgery in patients with connective tissue disease were explored. Clinicians should pay more attention to preoperative evaluation and intraoperative management in patients with risk factors.

3.
Int J Parasitol ; 53(8): 451-458, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37201563

RESUMO

Hookworms (genera Ancylostoma and Necator) are amongst the most prevalent and important parasites of humans globally. These intestinal parasites ingest blood, resulting in anemia, growth stunting, malnutrition, and adverse pregnancy outcomes. They are also critical parasites of dogs and other animals. In addition, hookworms and hookworm products are being explored for their use in treatment of autoimmune and inflammatory diseases. There is thus a significant and growing interest in these mammalian host-obligate parasites. Laboratory research is hampered by the lack of good means of cryopreservation and recovery of parasites. Here, we describe a robust method for long-term (≥3 year) cryopreservation and recovery of both Ancylostoma and Necator hookworms that is also applicable to two other intestinal parasites that passage through the infective L3 stage, Strongyloides ratti and Heligmosomoides polygyrus bakeri. The key is a revised recovery method, in which cryopreserved L1s are thawed and raised to the infective L3 stage using activated charcoal mixed with uninfected feces from a permissive host. This technique will greatly facilitate research on and availability of gastrointestinal parasitic nematodes with great importance to global health, companion animal health, and autoimmune/inflammatory disease therapies.


Assuntos
Infecções por Uncinaria , Enteropatias Parasitárias , Nematoides , Animais , Humanos , Cães , Ancylostomatoidea , Infecções por Uncinaria/veterinária , Ancylostoma , Enteropatias Parasitárias/veterinária , Criopreservação , Mamíferos
4.
PLoS Pathog ; 19(4): e1011285, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37011090

RESUMO

Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal of anthelmintic drugs that have historically reduced parasite burdens. However, anthelmintic resistance (AR) is increasing, and little is known about the molecular and genetic causes of resistance for most drugs. The free-living roundworm Caenorhabditis elegans has proven to be a tractable model to understand AR, where studies have led to the identification of molecular targets of all major anthelmintic drug classes. Here, we used genetically diverse C. elegans strains to perform dose-response analyses across 26 anthelmintic drugs that represent the three major anthelmintic drug classes (benzimidazoles, macrocyclic lactones, and nicotinic acetylcholine receptor agonists) in addition to seven other anthelmintic classes. First, we found that C. elegans strains displayed similar anthelmintic responses within drug classes and significant variation across drug classes. Next, we compared the effective concentration estimates to induce a 10% maximal response (EC10) and slope estimates of each dose-response curve of each strain to the laboratory reference strain, which enabled the identification of anthelmintics with population-wide differences to understand how genetics contribute to AR. Because genetically diverse strains displayed differential susceptibilities within and across anthelmintics, we show that C. elegans is a useful model for screening potential nematicides before applications to helminths. Third, we quantified the levels of anthelmintic response variation caused by genetic differences among individuals (heritability) to each drug and observed a significant correlation between exposure closest to the EC10 and the exposure that exhibited the most heritable responses. These results suggest drugs to prioritize in genome-wide association studies, which will enable the identification of AR genes.


Assuntos
Anti-Helmínticos , Nematoides , Infecções por Nematoides , Humanos , Animais , Caenorhabditis elegans , Estudo de Associação Genômica Ampla , Anti-Helmínticos/farmacologia , Nematoides/genética , Antinematódeos/farmacologia , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/genética , Infecções por Nematoides/parasitologia , Resistência a Medicamentos/genética
5.
Biotechnol Genet Eng Rev ; : 1-24, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36971244

RESUMO

Secondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity.Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production.

6.
bioRxiv ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36778351

RESUMO

Hookworms (genera Ancylostoma and Necator ) are amongst of the most prevalent and important parasites of humans globally. These intestinal parasites ingest blood, resulting in anemia, growth stunting, malnutrition, and adverse pregnancy outcomes. They are also critical parasites of dogs and other animals. In addition, hookworms and hookworm products are being explored for their use in treatment of autoimmune and inflammatory diseases. There is thus a significant and growing interest in these mammalian host-obligate parasites. Laboratory research is hampered by the lack of good means of cryopreservation. Here, we describe a robust method for long-term (≥3 year) cryoprotection and recovery of both Ancylostoma and Necator hookworms that is also applicable to two other intestinal parasites that passages through the infective third larval stage, Strongyloides ratti and H eligmosomoides polygyrus bakeri . The key is the use cryo-preserved first-staged larvae raised to the infective third larval stage using activated charcoal mixed with uninfected feces from a permissive host. This technique will greatly facilitate research on and availability of gastrointestinal parasitic nematodes with great importance to global health, companion animal health, and autoimmune/inflammatory disease therapies.

7.
Nanomicro Lett ; 15(1): 16, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36580150

RESUMO

Metal halide perovskites have generated significant attention in recent years because of their extraordinary physical properties and photovoltaic performance. Among these, inorganic perovskite quantum dots (QDs) stand out for their prominent merits, such as quantum confinement effects, high photoluminescence quantum yield, and defect-tolerant structures. Additionally, ligand engineering and an all-inorganic composition lead to a robust platform for ambient-stable QD devices. This review presents the state-of-the-art research progress on inorganic perovskite QDs, emphasizing their electronic applications. In detail, the physical properties of inorganic perovskite QDs will be introduced first, followed by a discussion of synthesis methods and growth control. Afterwards, the emerging applications of inorganic perovskite QDs in electronics, including transistors and memories, will be presented. Finally, this review will provide an outlook on potential strategies for advancing inorganic perovskite QD technologies.

8.
Microbiol Spectr ; 10(4): e0235622, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35946940

RESUMO

Bacillus thuringiensis (Bt) is a Gram-positive soil bacterium that is widely and safely applied in the environment as an insecticide for combatting insect pests that damage crops or are disease vectors. Dominant active ingredients made by Bt are insect-killing crystal (Cry) proteins released as crystalline inclusions upon bacterial sporulation. Some Bt Cry proteins, e.g., Cry5B (formally Cry5Ba1), target nematodes (roundworms) and show exceptional promise as anthelmintics (cures for parasitic nematode diseases). We have recently described inactivated bacteria with cytosolic crystal(s) (IBaCC) in which bioactive Bt Cry crystals (containing Cry5B) are fully contained within the cytosol of dead bacterial ghosts. Here, we demonstrate that these IBaCC-trapped Cry5B crystals can be liberated and purified away from cellular constituents, yielding purified cytosolic crystals (PCC). Cry5B PCC contains ~95% Cry5B protein out of the total protein content. Cry5B PCC is highly bioactive against parasitic nematode larvae and adults in vitro. Cry5B PCC is also highly active in vivo against experimental human hookworm and Ascaris infections in rodents. The process was scaled up to the 100-liter scale to produce PCC for a pilot study to treat two foals infected with the ascarid Parascaris spp. Single-dose Cry5B PCC brought the fecal egg counts of both foals to zero. These studies describe the process for the scalable production of purified Bt crystals and define a new and attractive pharmaceutical ingredient form of Bt Cry proteins. IMPORTANCE Bacillus thuringiensis crystal proteins are widely and safely used as insecticides. Recent studies have shown they also can cure gastrointestinal parasitic worm (nematode) infections when ingested. However, reproducible, scalable, and practical techniques for purifying these proteins have been lacking. Here, we address this severe limitation and present scalable and practical methods for large-scale purification of potently bioactive B. thuringiensis crystals and crystal proteins. The resultant product, called purified cytosolic crystals (PCC), is highly compatible with ingestible drug delivery and formulation. Furthermore, there are growing applications in agriculture and insect control where access to large quantities of purified crystal proteins is desirable and where these methods will find great utility.


Assuntos
Anti-Helmínticos , Bacillus thuringiensis , Nematoides , Animais , Anti-Helmínticos/uso terapêutico , Proteínas de Bactérias , Citosol , Cavalos , Humanos , Projetos Piloto
9.
Nanoscale ; 14(33): 11953-11962, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35899800

RESUMO

Accumulation of heavy metal ions, including copper ions (Cu2+), presents a serious threat to human health and to the environment. A substantial amount of research has focused on detecting such species in aqueous solutions. However, progress towards ultrasensitive and easy-to-use sensors for non-aqueous solutions is still limited. Here, we focus on the detection of copper species in hexane, realising ultra-sensitive detection through a fluorescence-based approach. To achieve this, a novel macroporous composite material has been developed featuring luminescent CsPbBr3 nanocrystals (NCs) chemically adhered to a polymerized high internal phase emulsion (polyHIPE) substrate through surface thiol groups. Due to this thiol functionality, sub-monolayer NC formation is realised, which also renders outstanding stability of the composite in the ambient environment. Copper detection is achieved through a direct solution based immersion of the CsPbBr3-(SH)polyHIPE composite, which results in concentration-dependent quenching of the NC photoluminescence. This newly developed sensor has a limit of detection (LOD) for copper as low as 1 × 10-16 M, and a wide operating window spanning 10-2 to 10-16 M. Moreover, the composite exhibits excellent selectivity among different transition metals.

10.
Cancer Biomark ; 32(3): 327-337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151835

RESUMO

BACKGROUND: Recent studies demonstrated the involvement of mesenchymal stem/stromal cells (MSCs) in carcinogenesis, but the molecular mechanism behind this transformation is still obscured. OBJECTIVE: To screen both the expression levels of polycomb and trithorax epigenetic regulators and TrP53 mutations in early and late MSC culture passages in an attempt to decipher the mechanism of spontaneous transformation. METHODS: The study was conducted on early and late passages of MSC culture model from C57BL/6J mice. The expression profile of 84 epigenetic regulators was examined using RT2 profiler PCR array. TrP53 mutations in the DNA binding domain was screened. Codons, amino acids positions and the corresponding human variants were detected in P53 sequences. RESULTS: Sixty-two epigenetic regulators were dysregulated. Abnormalities were detected starting the third passage. Nine regulators were dysregulated in all passages. (C>G) substitution P53 mutation was detected in passage 3 resulting in Ser152Arg substitution. Passages 6, 9, 12 and the last passage showed T>C substitution resulting in Cys235Arg substitution. The last passage had T deletion and A insertion resulting in frame shift mutations changing the p.Phe286Ser and p.Asn103Lys respectively. CONCLUSION: In vitro expanded MSCs undergo transformation through alteration of epigenetic regulators which results in genomic instability and frequent P53 mutations.


Assuntos
Epigênese Genética/genética , Proteína Supressora de Tumor p53/genética , Animais , Proliferação de Células , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Mutação
11.
Foods ; 10(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071798

RESUMO

Terpenes are naturally occurring compounds produced by plants that are of great commercial interest in the food, agricultural, cosmetic, and pharmaceutical industries due to their broad spectra of antibacterial, antifungal, anthelmintic, membrane permeation enhancement, and antioxidant biological activities. Applications of terpenes are often limited by their volatility and the need for surfactants or alcohols to produce stable, soluble (non-precipitated) products. Yeast particles (YPs) are hollow, porous microspheres that have been used for the encapsulation of terpenes (YP terpenes) by passive diffusion of terpenes through the porous YP cell walls. We here report the development of a second generation YP encapsulated terpene technology that incorporates the stimuli-responsive control of terpene release using biodegradable pro-terpene compounds (YP pro-terpenes). YP terpenes and YP pro-terpenes were both produced, in which high levels of carvacrol, eugenol, thymol and geraniol were encapsulated. The YP pro-terpenes show higher encapsulation stability than YP terpenes due to pro-terpenes being non-volatile solids at room temperature and stable in suspensions at neutral pH. YP pro-terpenes and YP terpenes were evaluated for biological activity in antibacterial, antifungal and anthelmintic assays. The YP pro-terpenes retained the full biological activity of the parent terpene compound.

12.
One Health ; 12: 100241, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33889707

RESUMO

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world.

13.
ACS Nano ; 15(1): 1454-1464, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33439631

RESUMO

The extensive use of halomethanes (CH3X, X = F, Cl, Br, I) as refrigerants, propellants, and pesticides has drawn serious concern due to their adverse biological and atmospheric impact. However, there are currently no portable rapid and accurate monitoring systems for their detection. This work introduces an approach for the selective and sensitive detection of halomethanes using photoluminescence spectral shifts in cesium lead halide perovskite nanocrystals. Focusing on iodomethane (CH3I) as a model system, it is shown that cesium lead bromide (CsPbBr3) nanocrystals can undergo rapid (<5 s) halide exchange, but only after exposure to oleylamine to induce nucleophilic substitution of the CH3I and release the iodide species. The extent of the halide exchange is directly dependent on the CH3I concentration, with the photoluminescence emission of the CsPbBr3 nanocrystals exhibiting a redshift of more than 150 nm upon the addition of 10 ppmv of CH3I. This represents the widest detection range and the highest sensitivity to the detection of halomethanes using a low-cost and portable approach reported to date. Furthermore, inherent selectivity for halomethanes compared to other organohalide analogues is achieved through the dramatic differences in their alkylation reactivity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33318013

RESUMO

Gastrointestinal nematodes (GINs) of humans, e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole anthelmintics. However, benzimidazole efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold chain, and massively scalable. Bacillus thuringiensis crystal protein 5B (Cry5B) has anthelmintic properties that could fill this void. Here, we developed an active pharmaceutical ingredient (API) containing B. thuringiensis Cry5B compatible with MDA. We expressed Cry5B in asporogenous B. thuringiensis during vegetative phase, forming cytosolic crystals. These bacteria with cytosolic crystals (BaCC) were rendered inviable (inactivated BaCC [IBaCC]) with food-grade essential oils. IBaCC potency was validated in vitro against nematodes. IBaCC was also potent in vivo against human hookworm infections in hamsters. IBaCC production was successfully scaled to 350 liters at a contract manufacturing facility. A simple fit-for-purpose formulation to protect against stomach digestion and powdered IBaCC were successfully made and used against GINs in hamsters and mice. A pilot histopathology study and blood chemistry workup showed that five daily consecutive doses of 200 mg/kg body weight Cry5B IBaCC (the curative single dose is 40 mg/kg) was nontoxic to hamsters and completely safe. IBaCC is a safe, inexpensive, highly effective, easy-to-manufacture, and scalable anthelmintic that is practical for MDA and represents a new paradigm for treating human GINs.


Assuntos
Anti-Helmínticos , Infecções por Uncinaria , Nematoides , Parasitos , Animais , Anti-Helmínticos/uso terapêutico , Proteínas de Bactérias , Criança , Cricetinae , Infecções por Uncinaria/tratamento farmacológico , Humanos , Camundongos
15.
Int J Parasitol Drugs Drug Resist ; 14: 230-236, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33242790

RESUMO

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.


Assuntos
Anti-Helmínticos , Hemoncose , Haemonchus , Nematoides , Probióticos , Doenças dos Ovinos , Animais , Anti-Helmínticos/uso terapêutico , Bovinos , Fezes , Feminino , Cabras , Hemoncose/tratamento farmacológico , Hemoncose/veterinária , Contagem de Ovos de Parasitas , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia
16.
Nanoscale ; 12(8): 4859-4867, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-31971209

RESUMO

The ligand assisted reprecipitation (LARP) technique is an accessible and facile method that can synthesize metal halide perovskite nanocrystals (PNCs) under ambient conditions. However, low product yields of less than 30% for LARP and its contemporary methods are indicative of highly inefficient reactions. In this work we apply the principles of green chemistry to the LARP technique for synthesizing CsPbBr3 PNCs and help address this issue. Through these efforts, high product yields of ∼70% are achieved using stochiometric Cs : Pb precursor ratios. This is realized by (i) substituting the conventional toluene (TOL) anti-solvent with ethyl acetate (EA) and (ii) replacing the conventionally used unsaturated oleylamine ligand with the shorter saturated octylamine ligand. These changes also result in a 60% molar reduction in total ligand concentration and a 62.5% reduction in solvent waste during purification. The synthesized PNCs are comparable to the TOL-LARP reference in crystal quality, morphology and phase, with their photoluminescence quantum yields being readily enhanced to over 80% through additions of RNH3Br ligands. The spectral versatility of these materials is demonstrated through post-synthetic chloride and iodide halide anion exchange, which readily yields tunable CsPbX3 derivatives across the visible spectrum. Our EA-LARP protocol is further shown to be readily upscaled to ∼0.5 L, while maintaining good nanocrystal properties and a product yield of 60%.

17.
Cell Cycle ; 18(23): 3313-3324, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590627

RESUMO

Long non-coding RNA (lncRNA) SNHG4 has been shown to be associated with the development of a variety of cancers. The purpose of this study was to investigate the effect of SNHG4 on cervical cancer (CC) and the corresponding mechanism. The qRT-PCR was used to determine the expressions of SNHG4 and miR-148a-3p in CC cell lines and tissues. Cell apoptosis and proliferation were measured by flow cytometry and MTT assay, respectively. The interaction between SNHG4, miR-148a-3p and c-Met was verified by bioinformatics, dual-luciferase reporter gene and RNA immunoprecipitation (RIP), and the effect of SNHG4 on the growth of CC tumor in vivo was explored. The expression of SNHG4 was increased in both CC cell lines and tissues, while the expression of miR-148a-3p was down-regulated. Meanwhile, silencing SNHG4 remarkably inhibited CC cell proliferation and promoted apoptosis. In addition, miR-148a-3p was a direct target gene of SNHG4, and down-regulation of miR-148a-3p could observably reverse the effect of silencing SNHG4 on the proliferation and apoptosis of CC cells. More importantly, SNHG4 could up-regulate the expression of c-Met by targeting and interacting with miR-148a-3p. Finally, in vivo experiments confirmed that silence SNHG4 down-regulated the expression of c-Met by promoting miR-148a-3p, and ultimately suppressed the growth of CC tumor in vivo. In conclusion, SNHG4 could be used as a competitive endogenous RNA to bind to miR-148a-3p, thereby up-regulating the expression of c-Met and ultimately promoting the progression of CC, which provided a potential therapeutic target for the targeted treatment of CC.


Assuntos
MicroRNAs/genética , Proteínas Proto-Oncogênicas c-met/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/patologia
18.
Electron. j. biotechnol ; 35: 10-17, sept. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1047827

RESUMO

Alanine mother liquor, a type of industrial waste from alanine fermentation, was used as a nitrogen source to produce docosahexaenoic acid (DHA) by Schizochytrium sp. B4D1. The results indicated that yeast extract could trigger the utilization of the alanine mother liquor. Additionally, the alanine can be quenched during the culture, which aids in DHA accumulation. The medium components were optimized via response surface methodology as follows: 99.98-g/L glucose, 0.05-g/L yeast extract and a 183.17 dilution factor of the alanine mother liquid (v/v, with an alanine content of 0.72 g/L) and 17.98% inoculum concentration (v/v). Finally, in a 50-mL shake-flask fermentation, the DHA yield was 2.29 g/L.


Assuntos
Ácidos Docosa-Hexaenoicos/biossíntese , Alanina/metabolismo , Estramenópilas/metabolismo , Leveduras , Peptídeos e Proteínas de Sinalização Intercelular/isolamento & purificação , Alanina/análise , Fermentação , Glucose , Resíduos Industriais
19.
World J Gastroenterol ; 21(22): 6884-91, 2015 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-26078564

RESUMO

AIM: To study the potential prognostic role of microRNA-382 (miR-382) in esophageal squamous cell carcinoma (ESCC). METHODS: Forty six patients were divided into 2 groups according to postoperative survival time: the poor outcome group (28 patients), who showed early metastasis but no recurrence, and died within 1 year after surgery, 12 patients of the group received postoperative chemotherapy treatment that was given after early metastasis happening; the good outcome group (18 patients), who had no clinical metastasis and recurrence, and survived 5 years or more after surgery, all patients did not receive any postoperative treatment. Total RNA was extracted from the patients' formalin-fixed and paraffin-embedded esophageal cancer tissues. miR-382 level was evaluated using high-throughput real-time quantitative polymerase chain reaction analysis. The correlation between miR-382 level and clinicopathologic features was analyzed through COX regression model, and Kaplan-Meier analysis was used to analyze the relationship between miR-382 level and patient survival time. RESULTS: miR-382 was differentially expressed in the two groups. Overall the average miR-382 level in the ESCC patients with good outcome was 9.8 ± 3.8, while miR-382 level in the ESCC patients with poor outcome was 3.0 ± 0.8. The differences of miR-382 levels between two groups were significant (P < 0.05). Kaplan-Meier analysis results showed that miR-382 expression level generally had a significant reverse-correlation with ESCC patient survival time (P < 0.001), in which the patients with higher expressions of miR-382 had a longer survival time either among individuals with the same tumor stage or among the overall patients. CONCLUSION: miR-382 levels are reverse-correlated with ESCC poor outcomes, suggesting that miR-382 could be a potential predictive biomarker for both prognosis and treatment of ESCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Regulação para Baixo , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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