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1.
Rev Endocr Metab Disord ; 25(3): 457-465, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38609701

RESUMO

The diagnostic approach to hypopituitarism involves many disciplines. Clinical symptoms rarely are specific. Imaging techniques are helpful but cannot prove the specific functional defects. Therefore, the definitive diagnosis of pituitary insufficiency is largely based on laboratory tests. However, also laboratory methods come with inherent limitations, and it is essential for the clinician to know and recognize typical pitfalls. Most factors potentially impairing the quality of hormone measurements are introduced in the preanalytical phase, i.e. before the hormones are measured by the laboratory. For example, the timing of blood drawing with respect to circadian rhythm, stress, and medication can have an influence on hormone concentrations. During the actual analysis of the hormones, cross-reactions with molecules present in the sample presenting the same or similar epitopes than the intended analyte may affect immunoassays. Interference can also come from heterophilic or human anti-animal antibodies. Unexpected problems can also be due to popular nutritional supplements which interfere with the measurement procedures. An important example in this respect is the interference from biotin. It became only clinically visible when the use of this vitamin became popular among patients. The extreme serum concentrations reached when patients take it as a supplement can lead to incorrect measurements in immunoassays employing the biotin-streptavidin system. To some extent, hormone analyses using liquid chromatography mass spectrometry (LCMS) can overcome problems, although availability and cost-effectiveness of this method still imposes restrictions. In the post-analytical phase, appropriateness of reference intervals and cut-offs with respect to the specific analytical method used is of outmost importance. Furthermore, for interpretation, additional biological and pharmacological factors like BMI, age and concomitant diseases must be considered to avoid misinterpretation of the measured concentrations. It is important for the clinician and the laboratory to recognize when one or more laboratory values do not match the clinical picture. In an interdisciplinary approach, the search for the underlying cause should be initiated.


Assuntos
Hipopituitarismo , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/sangue , Imunoensaio/métodos , Imunoensaio/normas
2.
Pestic Biochem Physiol ; 200: 105836, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582598

RESUMO

The striped stem borer, Chilo suppressalis (Walker), a notorious pest infesting rice, has evolved a high level of resistance to many commonly used insecticides. In this study, we investigate whether tyrosine hydroxylase (TH), which is required for larval development and cuticle tanning in many insects, could be a potential target for the control of C. suppressalis. We identified and characterized the full-length cDNA (CsTH) of C. suppressalis. The complete open reading frame of CsTH (MW690914) was 1683 bp in length, encoding a protein of 560 amino acids. Within the first to the sixth larval instars, CsTH was high in the first day just after molting, and lower in the ensuing days. From the wandering stage to the adult stage, levels of CSTH began to rise and reached a peak at the pupal stage. These patterns suggested a role for the gene in larval development and larval-pupal cuticle tanning. When we injected dsCsTH or 3-iodotyrosine (3-IT) as a TH inhibitor or fed a larva diet supplemented with 3-IT, there were significant impairments in larval development and larval-pupal cuticle tanning. Adult emergence was severely impaired, and most adults died. These results suggest that CsTH might play a critical role in larval development as well as larval-pupal tanning and immunity in C. suppressalis, and this gene could form a potential novel target for pest control.


Assuntos
Inseticidas , Mariposas , Oryza , Animais , Larva/genética , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Pupa , Mariposas/metabolismo , Oryza/metabolismo
3.
Medisan ; 28(2)abr. 2024.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1558515

RESUMO

Introducción: La odontología holística es parte de la medicina biológica o neurofocal, dirigida a la prevención, el diagnóstico y el tratamiento relacionados con las enfermedades del sistema estomatognático en correlación con otras estructuras anatómicas, a fin de tratar al paciente de manera integral, en cuerpo, mente y alma. Objetivo: Identificar la presencia de gingivitis crónica y de otros campos de interferencia en pacientes con artritis del hombro. Métodos: Se realizó un estudio observacional, descriptivo y transversal de 24 pacientes con artritis del hombro, pertenecientes al área de salud del Policlínico Docente Carlos Juan Finlay en Santiago de Cuba, quienes fueron atendidos en la Clínica Estomatológica Provincial Docente Mártires del Moncada, desde noviembre del 2021 hasta mayo del 2022. Resultados: En la serie predominaron el sexo femenino (62,5 %) y el grupo etario de 35-59 años (75,0 %). De igual modo, la mayoría de los pacientes padecía gingivitis crónica (87,5 %), en tanto, los otros campos de interferencia mayormente hallados fueron la placa dentobacteriana (100 %) y la caries dental (58,3 %), que figuraron en todos los molares según el holograma del microsistema de dientes alemán. Conclusiones: Los campos de interferencia identificados con más frecuencia en la casuística fueron la gingivitis crónica grave, la placa dentobacteriana y la caries dental, los cuales estuvieron asociados a la artritis del hombro que aquejaba a los pacientes.


Introduction: Holistic dentistry is part of the biological or neurofocal medicine, directed to the prevention, diagnosis and treatment related to the diseases of the stomatognatic system in correlation with other anatomical structures, in order to treat the patient in an integral way, in body, mind and soul. Objective: To identify the presence of chronic gingivitis and other interference fields in patients with shoulder arthritis. Methods: An observational, descriptive and cross-sectional study of 24 patients with shoulder arthritis was carried out, who belonged to the health area of Carlos Juan Finlay Teaching Polyclinic in Santiago de Cuba. They were assisted in Mártires del Moncada Teaching Provincial Stomatological Clinic, from November, 2021 to May, 2022. Results: In the series there was a prevalence of the female sex (62.5%) and the 35-59 age group (75.0%). In a same way, most of the patients suffered from chronic gingivitis (87.5%), as long as the other mostly found interference fields were the dentobacterial plaque (100%) and dental cavity (58.3%) that were in all the molars according to the hologram of the German teeth microsystem. Conclusions: Severe chronic gingivitis, dentobacterial plaque and dental cavity were the most frequently identified interference fields in the case material, which were associated to the shoulder arthritis in patients.

4.
Microorganisms ; 12(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38543639

RESUMO

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O3-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA interference, and microinjection. The O3-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O3-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O3Pc-MSP gene (Oms3) induced additional O3 mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates that this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O3Pc-MSP (Oms3) gene had nine silent mutations compared to the complementary mating type of the E3 homologue gene.

5.
Adv Sci (Weinh) ; 11(17): e2400862, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38408138

RESUMO

Hematoma, a risk factor of implant-associated infections (IAIs), creates a Fe-rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)-loaded layered double hydroxide (LDH)-based nanomedicine (DFP@Ga-LDH) that targets the Fe-rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga-LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga-LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe-associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga-LDH functions as a nano-adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga-LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga-LDH-Cefi. Antimicrobial and biosafety efficacies of DFP@Ga-LDH-Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma-created Fe-rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano-adjuvants as antibacterial agents.


Assuntos
Antibacterianos , Biofilmes , Ferro , Infecções Relacionadas à Prótese , Pseudomonas aeruginosa , Biofilmes/efeitos dos fármacos , Camundongos , Ferro/metabolismo , Animais , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Deferiprona/farmacologia , Modelos Animais de Doenças , Cefiderocol , Infecções por Pseudomonas/tratamento farmacológico , Humanos , Nanomedicina/métodos
6.
Eur J Case Rep Intern Med ; 11(1): 004188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38223283

RESUMO

Introduction: High blood concentrations of vitamin B12 are often caused by over-supplementation. However, there are instances in which augmented vitamin B12 levels are seen in the absence of supplements. Macro-vitamin B12 is an underrated cause of supra-physiological cobalamin plasma levels. Case description: A 70-year-old man was referred to an ambulatory internal medicine centre because of high vitamin B12 levels yet he denied taking supplements. An X-ray showed a tumour in the right upper lobe of the lung, which triggered further examinations. An MRI scan of the brain came back normal as well as a CT scan of the abdomen, and colonoscopy. The pulmonologist requested a PET-CT scan, which showed an isolated 18-FDG uptake in the area of the lung mass that was detected earlier. The patient underwent surgery with adjuvant cis-platinum and gemcitabine and is still making good progress. The vitamin B12 levels persisted after successful treatment of lung adenocarcinoma; determination of vitamin B12 after PEG (polyethylene glycol) precipitation showed normal concentrations. Discussion: A high vitamin B12 plasma concentration in the absence of vitamin supplementation can be a daunting diagnostic problem for the internist, as there are several possible underlying causes. In this case the diagnosis of lung carcinoma was made, the patient was treated appropriately, yet this pathology had no correlation with the cobalamin levels. Conclusion: A high vitamin B12 concentration can be the impetus of thorough medical inquiries. Internists should be careful not to forget macro-vitamin B12 as a possible source of falsely elevated vitamin B12 values. LEARNING POINTS: When encountering an otherwise unexplainable B12 hypervitaminosis, the diagnosis of macro-vitamin B12 should be taken into account to avoid unnecessary extensive medical examinations.PEG precipitation can distinguish between a 'real' high vitamin B12 and macro-vitamin B12.A high vitamin B12 concentration is no guarantee for adequate cobalamin storage. In case of suspicion, a vitamin B12 measurement after PEG precipitation should be considered.

7.
Pest Manag Sci ; 80(2): 905-909, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37822012

RESUMO

BACKGROUND: Implementation of resistance management tools is crucial for the continued efficacy of insect control technologies. An important aspect of insect resistance management (IRM) is the combined or sequential use of different modes-of-action to reduce selection pressure and delay evolution of resistance. This is especially important for insect pests with established ability to develop resistance to insecticides, such as the Colorado potato beetle (Leptinotarsa decemlineata, CPB). A new class of insecticides, based on double-stranded RNA (dsRNA) activating the gene silencing RNA-interference (RNAi) pathway, are currently under review for regulatory approval and commercial use in the USA against CPB. However, there is no information available on the potential for cross-resistance between RNAi insecticides and other classes of insecticides used against CPB. Herein, we aim to fill this knowledge gap by capitalizing on the availability of a CPB strain highly resistant to dsRNAs and test its susceptibility to diverse small-molecule insecticide classes compared to reference dsRNA-susceptible CPB strains. RESULTS: Differences in activity were observed among the four insecticides tested, with abamectin demonstrating highest activity against all three strains of CPB. However, no differences were observed among the dsRNA-resistant and susceptible CPB strains for any of the tested compounds. Overall, these results demonstrate lack of cross-resistance to commonly used chemical insecticides in the dsRNA-resistant strain of CPB. CONCLUSION: These data support the use of these different insecticide classes along with RNAi-based insecticides as part of an effective insect resistance management framework aimed at delaying resistance in CPB. © 2023 Society of Chemical Industry.


Assuntos
Besouros , Inseticidas , Praguicidas , Solanum tuberosum , Animais , Besouros/genética , Larva , Inseticidas/farmacologia , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/farmacologia , Praguicidas/farmacologia , Solanum tuberosum/genética , Interferência de RNA
8.
Plant Sci ; 340: 111937, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043729

RESUMO

Due to the increasing demand for high-quality and high fiber-yielding cotton (Gossypium spp.), research into the development of stress-resilient cotton cultivars has acquired greater significance. Various biotic and abiotic stressors greatly affect cotton production and productivity, posing challenges to the future of the textile industry. Moreover, the content and quality of cottonseed oil can also potentially be influenced by future environmental conditions. Apart from conventional methods, genetic engineering has emerged as a potential tool to improve cotton fiber quality and productivity. Identification and modification of genome sequences and the expression levels of yield-related genes using genetic engineering approaches have enabled to increase both the quality and yields of cotton fiber and cottonseed oil. Herein, we evaluate the significance and molecular mechanisms associated with the regulation of cotton agronomic traits under both normal and stressful environmental conditions. In addition, the importance of gossypol, a toxic phenolic compound in cottonseed that can limit consumption by animals and humans, is reviewed and discussed.


Assuntos
Gossypium , Gossipol , Humanos , Gossypium/metabolismo , Óleo de Sementes de Algodão/metabolismo , Fibra de Algodão , Gossipol/metabolismo , Genômica
9.
J Agric Food Chem ; 71(50): 20000-20010, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38059819

RESUMO

Olfaction is crucial for Empoasca onukii Matsuda to recognize odors from the host and nonhost plants, and it has been proposed that odorant binding proteins are directly required for odorant discrimination and represent potential targets of interest for pest control. Here, we cloned EonuOBP43 and expressed the recombinant EonuOBP43 protein. Furthermore, competitive fluorescence binding assays with 19 ligands indicated that terpenoids and alkanes showed a relatively higher than for other classes of chemicals. Additionally, ligand docking and site-directed mutagenesis results revealed that seven hydrophobic residues, including Val-86, Met-89, Phe-90, Ile-104, Ile-105, Leu-130, and Val-134, played a key role in the binding of EonuOBP43 to plant volatiles. In olfactometer tests, E. onukii were significantly attracted to α-farnesene and repelled to ß-caryophyllene, and dsOBP43 treated adult lost response to α-farnesene and ß-caryophyllene. In summary, our results demonstrated that EonuOBP43 may function as a carrier in the process of sensing plant compounds of E. onukii.


Assuntos
Hemípteros , Animais , Hemípteros/fisiologia , Chá
10.
Nanomicro Lett ; 16(1): 57, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110610

RESUMO

The severe dependence of traditional phase change materials (PCMs) on the temperature-response and lattice deficiencies in versatility cannot satisfy demand for using such materials in complex application scenarios. Here, we introduced metal ions to induce the self-assembly of MXene nanosheets and achieve their ordered arrangement by combining suction filtration and rapid freezing. Subsequently, a series of MXene/ K+/paraffin wax (PW) phase change composites (PCCs) were obtained via vacuum impregnation in molten PW. The prepared MXene-based PCCs showed versatile applications from macroscale technologies, successfully transforming solar, electric, and magnetic energy into thermal energy stored as latent heat in the PCCs. Moreover, due to the absence of binder in the MXene-based aerogel, MK3@PW exhibits a prime solar-thermal conversion efficiency (98.4%). Notably, MK3@PW can further convert the collected heat energy into electric energy through thermoelectric equipment and realize favorable solar-thermal-electric conversion (producing 206 mV of voltage with light radiation intensity of 200 mw cm-2). An excellent Joule heat performance (reaching 105 °C with an input voltage of 2.5 V) and responsive magnetic-thermal conversion behavior (a charging time of 11.8 s can achieve a thermal insulation effect of 285 s) for contactless thermotherapy were also demonstrated by the MK3@PW. Specifically, as a result of the ordered arrangement of MXene nanosheet self-assembly induced by potassium ions, MK3@PW PCC exhibits a higher electromagnetic shielding efficiency value (57.7 dB) than pure MXene aerogel/PW PCC (29.8 dB) with the same MXene mass. This work presents an opportunity for the multi-scene response and practical application of PCMs that satisfy demand of next-generation multifunctional PCCs.

11.
Curr Issues Mol Biol ; 45(11): 8733-8754, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37998726

RESUMO

An immunoassay is an analytical test method in which analyte quantitation is based on signal responses generated as a consequence of an antibody-antigen interaction. They are the method of choice for the measurement of a large panel of diagnostic markers. Not only are they fully automated, allowing for a short turnaround time and high throughput, but offer high sensitivity and specificity with low limits of detection for a wide range of analytes. Many immunoassay manufacturers exploit the extremely high affinity of biotin for streptavidin in their assay design architectures as a means to immobilize and detect analytes of interest. The biotin-(strept)avidin system is, however, vulnerable to interference with high levels of supplemental biotin that may cause elevated or suppressed test results. Since this system is heavily applied in clinical diagnostics, biotin interference has become a serious concern, prompting the FDA to issue a safety report alerting healthcare workers and the public about the potential harm of ingesting high levels of supplemental biotin contributing toward erroneous diagnostic test results. This review includes a general background and historical prospective of immunoassays with a focus on the biotin-streptavidin system, interferences within the system, and what mitigations are applied to minimize false diagnostic results.

12.
Biomolecules ; 13(10)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37892115

RESUMO

Glutamine: fructose-6-phosphate aminotransferase (GFAT), the fourth enzyme in the chitin synthesis pathway, exerts wide-ranging effects on the growth and development of organisms. However, the role of GFAT in Sogatella furcifera remains unknown. In this study, the functional significance of the GFAT gene of S. furcifera was analyzed using a reverse transcription-polymerase chain reaction and RNA interference (RNAi) analyses. The complementary DNA sequence of SfGFAT was 3162 bp in length and contained a 2067 bp open reading frame encoding 688 amino acid residues. Structural domain analysis indicated that the SfGFAT protein consisted of one glutamine aminotransferase class 2 domain and two sugar isomerase domains. Expression profile analysis revealed that SfGFAT was expressed throughout the egg, nymph, and adult phases and was strongly expressed on the first day of each nymph stage and in the integuments of five tissues. RNAi results revealed that SfGFAT gene silencing significantly inhibited the mRNA expression of the target gene and resulted in severe mortality among S. furcifera. In summary, these findings demonstrate that SfGFAT plays a critical role in the development of S. furcifera. Moreover, these results may aid in the development of methods to control the spread of S. furcifera.


Assuntos
Glutamina , Hemípteros , Animais , Sequência de Aminoácidos , Glutamina/metabolismo , Hemípteros/genética , Transaminases/metabolismo , Crescimento e Desenvolvimento
13.
Pestic Biochem Physiol ; 195: 105558, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37666594

RESUMO

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is an extremely destructive notifiable quarantine pest. Over the last two decades, neonicotinoid insecticides, particularly thiamethoxam and imidacloprid, have been used to control it in Xinjiang, and local field populations have developed different levels of resistance in consequence. However, the contributions of nicotinic acetylcholine receptors (nAChRs) to neonicotinoid resistance are currently poorly understood in CPB. Previous studies have shown that nAChRα1, α3, α8 and ß1 are major target subunits for neonicotinoids in some model and important agricultural insects including nAChRα1 subunit of L. decemlineata (Ldα1). In this study, the expression levels of Ldα3, Ldα8 and Ldß1 following 72 h of treatments with median lethal doses of thiamethoxam and imidacloprid were compared using real-time quantitative PCR. These genes were then individually and simultaneously knocked down with Ldα1 by RNA interference (RNAi) using a double-stranded RNA (dsRNA) feeding method for six days to explore their roles in CPB susceptibility to imidacloprid and thiamethoxam. The results showed that the expressions of Ldα3, Ldα8 and Ldß1 were significantly decreased by 36.99-74.89% after thiamethoxam and imidacloprid treatments, compared with the control. The significant downregulation of the target genes resulting from RNAi significantly reduced the mortality of adults exposed to thiamethoxam and imidacloprid by 34.53% -56.44% and 28.78%-43.93%, respectively. Furthermore, the adult survival rates were not affected by every dsRNA-feeding treatment, while the body weight of the test adults significantly deceased after four and six days of individual gene RNAi. This study showed that Ldα3, Ldα8 and Ldß1 are down-regulated by thiamethoxam and imidacloprid and play important roles in the tolerance of CPB to neonicotinoids.


Assuntos
Besouros , Solanum tuberosum , Animais , Besouros/genética , Tiametoxam , Neonicotinoides/farmacologia
14.
Acta Pharm Sin B ; 13(9): 3945-3955, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37719367

RESUMO

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

15.
Genes (Basel) ; 14(8)2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37628707

RESUMO

CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with CASK-related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of CASK-related disorders, research groups have employed diverse methods, including the generation of CASK knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate CASK mutant mice carrying missense mutations from patients with CASK-related disorders, allow us to understand the pathophysiology of CASK-related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of CASK-related disorders.


Assuntos
Microcefalia , Feminino , Animais , Camundongos , Masculino , Microcefalia/genética , Mutação , Camundongos Knockout , Fenótipo , Doenças Raras
16.
Small ; 19(49): e2304370, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37587781

RESUMO

Reprogramming the immunologically "cold" environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator (CuS/Z@M4T1 ) is detailed by engineering a Zn2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M4T1 rapidly causes intracellular Zn2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Humanos , Adjuvantes Imunológicos , Biomimética , Fototerapia , Neoplasias/terapia , Imunoterapia , Linhagem Celular Tumoral
17.
ACS Appl Mater Interfaces ; 15(29): 34578-34587, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37439604

RESUMO

Monitoring the force of fingertip manipulation without disturbing the natural sense of touch is crucial for digitizing the skills of experienced craftsmen. However, conventional force sensors need to be put between the skin and the objects, which affects the natural sense of the skin. Here, we proposed a fingertip force sensing method based on changes of blood volume and designed a wearable photoelectric fingertip force sensing system (PFFS) for digitalization of traditional Chinese medicine (TCM) pulse diagnosis. The PFFS does not interfere with the fingertips' tactile sense while detecting fingertip force. This PFFS detects the change of blood volume in fingertip by photoelectric plethysmography and can obtain the change of output current under different fingertip forces. We also studied the effect of various factors on PFFS output signals, including emission lights of different wavelengths, ambient temperature, and the user's heartbeat artifact. We further established the relationship between the change of blood volume and fingertip force by combining experimental and theoretical methods. Moreover, we demonstrated the feasibility of the PFFS to detect fingertip forces under commonly used conditions in TCM pulse diagnosis without sensory interference. This PFFS also shows promise for perceiving the viscosity of objects and recognizing gestures in human-computer interaction. This work paves the way for the digitalization of fingertip forces during TCM pulse diagnosis and other fingertip forces under natural conditions.


Assuntos
Dedos , Dispositivos Eletrônicos Vestíveis , Humanos , Tato , Fenômenos Mecânicos , Volume Sanguíneo
18.
J Spinal Cord Med ; : 1-12, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37428448

RESUMO

CONTEXT: Neuropathic pain is a common and debilitating condition following SCI. While treatments for neuropathic pain intensity have been reviewed, the impact on pain interference has not been summarized. OBJECTIVE: To systematically review the effect of neuropathic pain interventions on pain interference in individuals with spinal cord injury. METHODS: This systematic review included randomized controlled trials and quasi-experimental (non-randomized) studies which assessed the impact of an intervention on pain interference in individuals with spinal cord injury and neuropathic pain. Articles were identified by searching MEDLINE (1996 to April 11, 2022), EMBASE (1996 to April 11, 2022), PsycInfo (1987 to April, week 2, 2022). Studies were assessed for methodologic quality using a modified GRADE approach and were given quality of evidence (QOE) scores on a 4-point scale ranging from very low to high. RESULTS: Twenty studies met the inclusion criteria. These studies fell into the following categories: anticonvulsants (n = 2), antidepressants (n = 1), analgesics (n = 1), antispasmodics (n = 1), acupuncture (n = 2), transcranial direct current stimulation (n = 1), active cranial electrotherapy stimulation (n = 2), transcutaneous electrical nerve stimulation (n = 2), repetitive transcranial magnetic stimulation (n = 1), functional electrical stimulation (n = 1), meditation and imagery (n = 1), self-hypnosis and biofeedback (n = 1), and interdisciplinary pain programs (n = 4). CONCLUSION: When considering studies of moderate to high quality, pregabalin, gabapentin, intrathecal baclofen, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (in 1 of 2 studies) were shown to have beneficial effects on pain interference. However, due to the low number of high-quality studies further research is required to confirm the efficacy of these interventions prior to recommending their use to reduce pain interference.

19.
J Steroid Biochem Mol Biol ; 233: 106360, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37429547

RESUMO

Retinoid X receptor (RXR) is a member of the ligand-dependent nuclear receptor family. Previous studies revealed that RXRs are involved in reproduction in vertebrates. However, information on the function of RXRs in turtles is scarce. In this study, the Rxrγ cDNA sequence of Pelodiscus sinensis was cloned and analyzed, and a polyclonal antibody was constructed. RXRγ protein showed a positive signal in both mature and differentiated gonads of the turtle. Subsequently, the function of the Rxrγ gene in gonadal differentiation was confirmed using short interfering RNA (RNAi). The full-length cDNA sequence of the Rxrγ gene in P. sinensis was 2152 bp, encoding 407 amino acids and containing typical nuclear receptor family domains, including the DNA-binding domain (DBD), ligand-binding domain (LBD), and activation function 1 (AF1). Moreover, gonadal Ps-Rxrγ showed sexual dimorphism expression patterns in differentiated gonads. Real-time quantitative PCR results revealed that the Rxrγ gene was highly expressed in the turtle ovary. RNAi treatment increased the number of Sertoli cells in ZZ embryonic gonads. Furthermore, RNA interference upregulated Dmrt1 and Sox9 in ZZ and ZW embryonic gonads. However, Foxl2, Cyp19a1, Stra8, and Cyp26b1 were downregulated in embryonic gonads. The results indicated that Rxrγ participated in gonadal differentiation and development in P. sinensis.


Assuntos
Tartarugas , Masculino , Animais , Feminino , Tartarugas/genética , DNA Complementar , Ligantes , Gônadas , Diferenciação Celular
20.
Ann Clin Lab Sci ; 53(3): 482-484, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37437939

RESUMO

OBJECTIVE: We reported significant interference of biotin in FT3 and FT4 assays using Beckman DXI 800 analyzer. Recently we acquired Alinity i analyzer where TSH, FT3 and FT4 assays are not biotin based. We hypothesized that if thyroid function tests on DXI 800 and Alinity i are harmonized, then it is possible to eliminate biotin interference. METHODS: We investigated assay harmonization by analyzing 35 specimens for TSH, FT4 and FT3 using both analyzers. We prepared one serum pool using left-over specimens where thyroid tests were ordered. Then aliquots of the pool were supplemented with various amounts of biotin followed by measuring thyroid function tests again. RESULTS: We observed assay harmonization between both analyzers for TSH, FT3 and FT4 Tests. TSH assay was not affected in the presence of biotin, but FT3 and FT4 values were significantly elevated using DXI 800 analyzer. In contrast, TSH, FT3 and FT4 assays were not affected by biotin using Alinity i analyzer. CONCLUSIONS: Elevated FT3 and FT4 using DXI 800 analyzer may be due to biotin interference which can be eliminated by observing normal values using Alinity i analyzer. However, normal or slightly elevated TSH with elevated FT3 and FT4 using both analyzers may indicate rare type of TSH producing tumor of pituitary, not biotin interference.


Assuntos
Bioensaio , Testes de Função Tireóidea , Humanos , Biotina , Suplementos Nutricionais , Tireotropina
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