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1.
J Vis Exp ; (207)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829118

RESUMO

Developing objective and quantitative methods of early gross motor assessment is essential to better understand neurodevelopment and to support early therapeutic interventions. Here, we present a method to quantify gross motor performance using a multisensor wearable, MAIJU (Motility Assessment of Infants with a JUmpsuit), which offers an automated, scalable, quantitative, and objective assessment using a fully automated cloud-based pipeline. This wearable suit is equipped with four movement sensors that record synchronized data to a mobile phone utilizing a low-energy Bluetooth connection. An offline analysis in the cloud server generates fully analyzed results within minutes for each recording. These results include a graphical report of the recording session and a detailed result matrix that gives second-by-second classifications for posture, movement, infant carrying, and free playtime. Our recent results show the virtue of such quantified motor assessment providing a potentially effective method for distinguishing variations in the infant's gross motor development.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Lactente , Destreza Motora/fisiologia , Desenvolvimento Infantil/fisiologia
2.
Appl Environ Microbiol ; 90(6): e0024424, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38780510

RESUMO

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase, and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, demonstrate complex formation between TclI, TclJ, and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core. IMPORTANCE: Thiopeptides are a family of antimicrobial peptides characterized for having sulfur-containing heterocycles and for being highly post-translationally modified. Numerous thiopeptides have been identified; almost all of which inhibit protein synthesis in gram-positive bacteria. These intrinsic antimicrobial properties make thiopeptides promising candidates for the development of new antibiotics. The thiopeptide micrococcin is synthesized by the ribosome and undergoes several post-translational modifications to acquire its bioactivity. In this study, we identify key interactions within the enzymatic complex that carries out cysteine to thiazole conversion in the biosynthesis of micrococcin.


Assuntos
Bacteriocinas , Cisteína , Tiazóis , Tiazóis/metabolismo , Cisteína/metabolismo , Bacteriocinas/metabolismo , Bacteriocinas/química , Bacteriocinas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Processamento de Proteína Pós-Traducional , Escherichia coli/genética , Escherichia coli/metabolismo
3.
Cureus ; 16(4): e57475, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38699131

RESUMO

Background Low back pain (LBP) is a common musculoskeletal condition that affects individuals worldwide, causing difficulties in daily tasks and social interactions. It can be categorized based on chronicity, with acute, subacute, and chronic forms. The causes of backache vary among patients and can include inflammatory conditions, radiculopathy, pregnancy, trauma, osteoporosis, nerve root compression, cancer, plexopathy, infection, and other spinal diseases. Aim The aim is to investigate the association between COVID-19 infection and LBP between all Saudi adults and foreign adults who had positive COVID-19 tests in the eastern region of Saudi Arabia. Methods A cross-sectional study was conducted in the Eastern Province of Saudi Arabia over the period from March 2023 to August 2023. Participants were selected by using a convenience sampling method, a sample (n=500) of individuals. The structured questionnaire was used to gather information on sociodemographic variables and COVID-related features. All the statistical calculations were performed using the SPSS software (by IBM) version 29.0.0. Results 482 participants completed the questionnaire. Out of 482 participants, the majority were females with a number of 372 (77.2%) aged between 20 and 29 years (38.4%). Out of the remaining participants, 110 (22.8%) were males. Most of the participants with a number of 301 (62.4%) were from the Hasa province. This was followed by Qatif (79, 16.4%), Dammam (56, 11.6%), Jubail (25, 5.2%), and others (21, 4.4%). The study revealed that 10.1% of participants reported experiencing back pain. The duration of backaches varied among respondents, with 122 (25.3%) experiencing them from a day to a week, 28 (5.8%) enduring them for six weeks, and 65 (13.5%) reporting a duration of six to 12 weeks. The majority, comprising 267 (55.4%) respondents, were uncertain about the period of their backaches. The prevalence of COVID-19 infection among the participants was 357 (74.1%), and 477 (99.0%) had been vaccinated against COVID-19. Approximately 44.4% of the participants experienced back pain, and out of those, 28.2% reported having pain during quarantine. Among the individuals with back pain, 24.7% attributed it to COVID-19. Conclusion This study highlights the significant correlation between back pain and COVID-19, even after the resolution of other symptoms. It underscores the importance of further research into the long-term effects and mechanisms of this association. The findings emphasize the need for healthcare professionals to consider back pain as a potential aspect of the post-COVID-19 symptom profile, ensuring comprehensive care for affected individuals.

4.
Cureus ; 16(4): e59385, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694651

RESUMO

The field of organ transplantation, particularly heart transplantation, has brought to light interesting phenomena challenging traditional understandings of memory, identity, and consciousness. Studies indicate that heart transplant recipients may exhibit preferences, emotions, and memories resembling those of the donors, suggesting a form of memory storage within the transplanted organ. Mechanisms proposed for this memory transfer include cellular memory, epigenetic modifications, and energetic interactions. Moreover, the heart's intricate neural network, often referred to as the "heart brain," communicates bidirectionally with the brain and other organs, supporting the concept of heart-brain connection and its role in memory and personality. Additionally, observations from hemispherectomy procedures highlight the brain's remarkable plasticity and functional preservation beyond expectations, further underscoring the complex interplay between the brain, body, and identity. However, ethical and philosophical questions regarding the implications of these findings, including the definition of death and the nature of personal identity, remain unresolved. Further interdisciplinary research is needed to unravel the intricacies of memory transfer, neuroplasticity, and organ integration, offering insights into both organ transplantation and broader aspects of neuroscience and human identity. Understanding these complexities holds promise for enhancing patient care in organ transplantation and deepens our understanding of fundamental aspects of human experience and existence.

5.
EBioMedicine ; 102: 105061, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537603

RESUMO

BACKGROUND: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. METHODS: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). FINDINGS: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69-1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30-1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90-2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). INTERPRETATION: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. FUNDING: This research was supported by the National Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.


Assuntos
Encéfalo , Gráficos de Crescimento , Humanos , Criança , Adolescente , Estudos Transversais , Redes Neurais de Computação , Eletroencefalografia
6.
Clin Proteomics ; 21(1): 23, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481131

RESUMO

BACKGROUND: Human tear protein biomarkers are useful for detecting ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strip; SS and microcapillary tube; MCT) have significant drawbacks, such as pain, risk of injury, sampling difficulty, and proteomic disparities between methods. Here, we present an alternative tear protein sampling method using soft contact lenses (SCLs). RESULTS: We optimized the SCL protein sampling in vitro and performed in vivo studies in 6 subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60 ± 31 µg of protein per eye. We also performed objective and subjective assessments of all sampling methods. Signs of irritation post-sampling were observed with SS but not with MCT and SCLs. Proteomic analysis by mass spectrometry (MS) revealed that all sampling methods resulted in the detection of abundant tear proteins. However, smaller subsets of unique and shared proteins were identified, particularly for SS and MCT. Additionally, there was no significant intrasubject variation between MCT and SCL sampling. CONCLUSIONS: These experiments demonstrate that SCLs are an accessible tear-sampling method with the potential to surpass current methods in sampling basal tears.

7.
J Mammary Gland Biol Neoplasia ; 29(1): 5, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416267

RESUMO

The three-dimensional (3D) structure of the ductal epithelium and the surrounding extracellular matrix (ECM) are integral aspects of the breast tissue, and they have important roles during mammary gland development, function and malignancy. However, the architecture of the branched mammary epithelial network is poorly recapitulated in the current in vitro models. 3D bioprinting is an emerging approach to improve tissue-mimicry in cell culture. Here, we developed and optimized a protocol for 3D bioprinting of normal and cancerous mammary epithelial cells into a branched Y-shape to study the role of cell positioning in the regulation of cell proliferation and invasion. Non-cancerous cells formed continuous 3D cell networks with several organotypic features, whereas the ductal carcinoma in situ (DCIS) -like cancer cells exhibited aberrant basal polarization and defective formation of the basement membrane (BM). Quantitative analysis over time demonstrated that both normal and cancerous cells proliferate more at the branch tips compared to the trunk region of the 3D-bioprinted cultures, and particularly at the tip further away from the branch point. The location-specific rate of proliferation was independent of TGFß signaling but invasion of the DCIS-like breast cancer cells was reduced upon the inhibition of TGFß. Thus, our data demonstrate that the 3D-bioprinted cells can sense their position in the branched network of cells and proliferate at the tips, thus recapitulating this feature of mammary epithelial branching morphogenesis. In all, our results demonstrate the capacity of the developed 3D bioprinting method for quantitative analysis of the relationships between tissue structure and cell behavior in breast morphogenesis and cancer.


Assuntos
Bioimpressão , Carcinoma Intraductal não Infiltrante , Humanos , Células Epiteliais , Epitélio , Fator de Crescimento Transformador beta
8.
Gastroenterology ; 166(5): 826-841.e19, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38266738

RESUMO

BACKGROUND & AIMS: Incapacitated regulatory T cells (Tregs) contribute to immune-mediated diseases. Inflammatory Tregs are evident during human inflammatory bowel disease; however, mechanisms driving the development of these cells and their function are not well understood. Therefore, we investigated the role of cellular metabolism in Tregs relevant to gut homeostasis. METHODS: Using human Tregs, we performed mitochondrial ultrastructural studies via electron microscopy and confocal imaging, biochemical and protein analyses using proximity ligation assay, immunoblotting, mass cytometry and fluorescence-activated cell sorting, metabolomics, gene expression analysis, and real-time metabolic profiling utilizing the Seahorse XF analyzer. We used a Crohn's disease single-cell RNA sequencing dataset to infer the therapeutic relevance of targeting metabolic pathways in inflammatory Tregs. We examined the superior functionality of genetically modified Tregs in CD4+ T-cell-induced murine colitis models. RESULTS: Mitochondria-endoplasmic reticulum appositions, known to mediate pyruvate entry into mitochondria via voltage-dependent anion channel 1 (VDAC1), are abundant in Tregs. VDAC1 inhibition perturbed pyruvate metabolism, eliciting sensitization to other inflammatory signals reversible by membrane-permeable methyl pyruvate supplementation. Notably, interleukin (IL) 21 diminished mitochondria-endoplasmic reticulum appositions, resulting in enhanced enzymatic function of glycogen synthase kinase 3 ß, a putative negative regulator of VDAC1, and a hypermetabolic state that amplified Treg inflammatory response. Methyl pyruvate and glycogen synthase kinase 3 ß pharmacologic inhibitor (LY2090314) reversed IL21-induced metabolic rewiring and inflammatory state. Moreover, IL21-induced metabolic genes in Tregs in vitro were enriched in human Crohn's disease intestinal Tregs. Adoptively transferred Il21r-/- Tregs efficiently rescued murine colitis in contrast to wild-type Tregs. CONCLUSIONS: IL21 triggers metabolic dysfunction associated with Treg inflammatory response. Inhibiting IL21-induced metabolism in Tregs may mitigate CD4+ T-cell-driven chronic intestinal inflammation.


Assuntos
Colite , Mitocôndrias , Animais , Humanos , Camundongos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Doença Crônica , Colite/imunologia , Colite/metabolismo , Colite/patologia , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Interleucinas/metabolismo , Interleucinas/farmacologia , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Linfócitos T Reguladores/imunologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Canal de Ânion 1 Dependente de Voltagem/genética
9.
Digit Health ; 9: 20552076231216681, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047163

RESUMO

Objective: The objective of this study was to evaluate the effectiveness of deep learning methods in detecting dental caries from radiographic images. Methods: A total of 771 bitewing radiographs were divided into two groups: adult (n = 554) and pediatric (n = 217). Two distinct semantic segmentation models were constructed for each group. They were manually labeled by general dentists for semantic segmentation. The inter-examiner reliability of the two examiners was also measured. Finally, the models were trained using transfer learning methodology along with computer science advanced tools, such as ensemble U-Nets with ResNet50, ResNext101, and Vgg19 as the encoders, which were all pretrained on ImageNet weights using a training dataset. Results: Intersection over union (IoU) score was used to evaluate the outcomes of the deep learning model. For the adult dataset, the IoU averaged 98%, 23%, 19%, and 51% for zero, primary, moderate, and advanced carious lesions, respectively. For pediatric bitewings, the IoU averaged 97%, 8%, 17%, and 25% for zero, primary, moderate, and advanced caries, respectively. Advanced caries was more accurately detected than primary caries on adults and pediatric bitewings P < 0.05. Conclusions: The proposed deep learning models can accurately detect advanced caries in permanent or primary bitewing radiographs. Misclassification mostly occurs between primary and moderate caries. Although the model performed well in correctly classifying the lesions, it can misclassify one as the other or does not accurately capture the depth of the lesion at this early stage.

10.
bioRxiv ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37961320

RESUMO

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, we demonstrate complex formation between TclI, TclJ and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core.

11.
Crit Rev Food Sci Nutr ; : 1-25, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37599624

RESUMO

Nanoencapsulation has found numerous applications in the food and nutraceutical industries. Micro and nanoencapsulated forms of bioactives have proven benefits in terms of stability, release, and performance in the body. However, the encapsulated ingredient is often subjected to a wide range of processing conditions and this is followed by storage, consumption, and transit along the gastrointestinal tract. A strong understanding of the fate of nanoencapsulates in the biological system is mandatory as it provides valuable insights for ingredient selection, formulation, and application. In addition to their efficacy, there is also the need to assess the safety of ingested nanoencapsulates. Given the rising research and commercial focus of this subject, this review provides a strong focus on their interaction factors and mechanisms, highlighting their prospective biological fate. This review also covers various approaches to studying the fate of nanoencapsulates in the body. Also, with emphasis on the overall scope, the need for a new advanced integrated common methodology to evaluate the fate of nanoencapsulates post-administration is discussed.

12.
Adv Orthop ; 2023: 6793645, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275323

RESUMO

Background: Early and proper screening for developmental dysplasia of the hip (DDH) is very critical to prevent catastrophic complication on the developing hip joint. Many factors (either maternal or child-related) that hinder timely DDH screening have been previously investigated. Methods: A cross-sectional descriptive study design was adopted. 175 babies presented for DDH screening coming with their mothers were investigated. Maternal age, age group, and educational level were recorded. In addition, multiple child-related variables such as age of screening, gender, positive family history, preterm delivery, and mode of delivery were recorded as well. Analysis for association between delayed vs. early screening was made against the maternal and the child-related variables. Results: A total number of 175 children with their mothers were investigated. The mean maternal age was 27.9 years, about one third of the mothers had a graduate level of education (36.3%), while 41.1% had high school education, and 22.3% had middle school education. On the other hand, 40.0% of the investigated babies were first born and two thirds of our sample babies were females (66.9%). Of the included babies, 100 (57.1%) were screened at the appropriate 4-month age, while 75 (42.9%) missed the 4-month screening. Chi-square analysis showed that delayed DDH screening was associated with a lower maternal educational level (P ≤ 0.001), younger maternal age (P ≤ 0.001), and first born baby (P ≤ 0.001). Positive family history was protective against delayed DDH screening (P = 0.032). Conclusion: The lower maternal educational level, younger maternal age group, and first born babies are risk factors for delayed DDH screening.

13.
J Enzyme Inhib Med Chem ; 38(1): 2220084, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37318308

RESUMO

Boronic acids/esters have recently emerged in the field of medicinal and pharmaceutical research due to their exceptional oxophilicity, low toxicity, and unique structure. They are known as potent enzyme inhibitors, cancer therapy capture agents, and can mimic certain types of antibodies to fight infections. They have been designed and developed into drugs, and this approach has emerged in the last 20 years. Five boronic acid drugs have been approved by the FDA and Health Canada, two of which are used to treat cancer, specifically multiple myeloma. The purpose of this review is to investigate boronic acid/ester derivatives as potential pharmaceutical agents as well as the mechanism of action. It will concentrate on six types of cancer: multiple myeloma, prostate cancer, breast cancer, lung cancer, cervical cancer, and colon cancer. Some newly developed boron-containing compounds have already demonstrated highly promising activities, but further investigation is required before final conclusions can be drawn.


Assuntos
Mieloma Múltiplo , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Ésteres/química , Mieloma Múltiplo/tratamento farmacológico , Ácidos Borônicos/farmacologia , Compostos de Boro/química
14.
EBioMedicine ; 92: 104591, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37137181

RESUMO

BACKGROUND: Early neurodevelopmental care and research are in urgent need of practical methods for quantitative assessment of early motor development. Here, performance of a wearable system in early motor assessment was validated and compared to developmental tracking of physical growth charts. METHODS: Altogether 1358 h of spontaneous movement during 226 recording sessions in 116 infants (age 4-19 months) were analysed using a multisensor wearable system. A deep learning-based automatic pipeline quantified categories of infants' postures and movements at a time scale of seconds. Results from an archived cohort (dataset 1, N = 55 infants) recorded under partial supervision were compared to a validation cohort (dataset 2, N = 61) recorded at infants' homes by the parents. Aggregated recording-level measures including developmental age prediction (DAP) were used for comparison between cohorts. The motor growth was also compared with respective DAP estimates based on physical growth data (length, weight, and head circumference) obtained from a large cohort (N = 17,838 infants; age 4-18 months). FINDINGS: Age-specific distributions of posture and movement categories were highly similar between infant cohorts. The DAP scores correlated tightly with age, explaining 97-99% (94-99% CI 95) of the variance at the group average level, and 80-82% (72-88%) of the variance in the individual recordings. Both the average motor and the physical growth measures showed a very strong fit to their respective developmental models (R2 = 0.99). However, single measurements showed more modality-dependent variation that was lowest for motor (σ = 1.4 [1.3-1.5 CI 95] months), length (σ = 1.5 months), and combined physical (σ = 1.5 months) measurements, and it was clearly higher for the weight (σ = 1.9 months) and head circumference (σ = 1.9 months) measurements. Longitudinal tracking showed clear individual trajectories, and its accuracy was comparable between motor and physical measures with longer measurement intervals. INTERPRETATION: A quantified, transparent and explainable assessment of infants' motor performance is possible with a fully automated analysis pipeline, and the results replicate across independent cohorts from out-of-hospital recordings. A holistic assessment of motor development provides an accuracy that is comparable with the conventional physical growth measures. A quantitative measure of infants' motor development may directly support individual diagnostics and care, as well as facilitate clinical research as an outcome measure in early intervention trials. FUNDING: This work was supported by the Finnish Academy (314602, 335788, 335872, 332017, 343498), Finnish Pediatric Foundation (Lastentautiensäätiö), Aivosäätiö, Sigrid Jusélius Foundation, and HUS Children's Hospital/HUS diagnostic center research funds.


Assuntos
Desenvolvimento Infantil , Dispositivos Eletrônicos Vestíveis , Lactente , Humanos , Criança , Gráficos de Crescimento , Postura
15.
J Chromatogr A ; 1701: 464044, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37196519

RESUMO

Offline peptide separation (PS) using high-performance liquid chromatography (HPLC) is currently used to enhance liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of proteins. In search of more effective methods for enhancing MS proteome coverage, we developed a robust method for intact protein separation (IPS), an alternative first-dimension separation technique, and explored additional benefits that it offers. Comparing IPS to the traditional PS method, we found that both enhance detection of unique protein IDs to a similar magnitude, though in diverse ways. IPS was especially effective in serum, which has a small number of extremely high abundance proteins. PS was more effective in tissues with fewer dominating high-abundance proteins and was more effective in enhancing detection of post-translational modifications (PTMs). Combining the IPS and PS methods together (IPS+PS) was especially beneficial, enhancing proteome detection more than either method could independently. The comparison of IPS+PS versus six PS fractionation pools increased total number of proteins IDs by nearly double, while also significantly increasing number of unique peptides detected per protein, percent peptide sequence coverage of each protein, and detection of PTMs. This IPS+PS combined method requires fewer LC-MS/MS runs than current PS methods would need to obtain similar improvements in proteome detection, and it is robust, time- and cost-effective, and generally applicable to various tissue and sample types.


Assuntos
Proteoma , Proteômica , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Proteoma/análise , Proteômica/métodos , Espectrometria de Massas em Tandem , Peptídeos/análise
16.
Diagnostics (Basel) ; 13(4)2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36832075

RESUMO

Binding densities to dopamine D1-like and D2-like receptors (D1DR and D2DR) were studied in brain regions of animals with genetic generalized audiogenic (AGS) and/or absence (AbS) epilepsy (KM, WAG/Rij-AGS, and WAG/Rij rats, respectively) as compared to non-epileptic Wistar (WS) rats. Convulsive epilepsy (AGS) exerted a major effect on the striatal subregional binding densities for D1DR and D2DR. An increased binding density to D1DR was found in the dorsal striatal subregions of AGS-prone rats. Similar changes were seen for D2DR in the central and dorsal striatal territories. Subregions of the nucleus accumbens demonstrated consistent subregional decreases in the binding densities of D1DR and D2DR in epileptic animals, irrespective of epilepsy types. This was seen for D1DR in the dorsal core, dorsal, and ventrolateral shell; and for D2DR in the dorsal, dorsolateral, and ventrolateral shell. An increased density of D2DR was found in the motor cortex of AGS-prone rats. An AGS-related increase in binding densities to D1DR and D2DR in the dorsal striatum and motor cortex, areas responsible for motor activity, possibly reflects the activation of brain anticonvulsive loops. General epilepsy-related decreases in binding densities to D1DR and D2DR in the accumbal subregions might contribute to behavioral comorbidities of epilepsy.

17.
Food Chem ; 406: 135035, 2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-36481513

RESUMO

Considering the growing concern of iron and folic acid deficiency, encapsulation of these nutrients and fortification into foods is emerging as an effective counter-strategy. The present work focuses on a scalable approach for the production of iron, ascorbic acid, and folic acid core-shell encapsulates using novel 3-fluid nozzle (3FN) spray drying with whey protein as core and either pectin or hydroxypropyl methylcellulose (HPMC) as shell polymers. The effect of shell formation was observed by comparing core-shell encapsulates with conventional 2-fluid nozzle (2FN) encapsulates. Also, the effect of pH of whey protein on the color of encapsulates is noteworthy; reducing the pH to 4.0 significantly improved the lightness value (52.91 ± 0.13) when compared with the encapsulates with native pH (38.91 ± 0.58). Furthermore, sample with pectin as shell polymer exhibited fair flowability with lowest values of Hausner ratio (1.25 ± 0.04) and Carr's index (20.06 ± 2.71) and highest encapsulation efficiency for folic acid (86.07 ± 5.24%). Whereas, encapsulates having HPMC as shell polymer showed highest lightness value (60.80 ± 0.32) and highest encapsulation efficiency for iron (87.28 ± 4.15%). The formation of core-shell structure was confirmed by evaluation of the surface composition which showed reduced amine bonds and increased aliphatic and carbonyl bonds in the encapsulates prepared by 3FN spray drying. The encapsulates prepared without adjusting whey protein pH showed the least release (∼51 % in 24 h) and bioaccessibility (∼56%) of iron indicating the iron-whey protein complex formation. Based on appearance, smooth surface morphology, flowability, and release behavior, a combination of whey protein and pectin is recommended for co-encapsulation of iron, folic acid and ascorbic acid.


Assuntos
Secagem por Atomização , Vitaminas , Proteínas do Soro do Leite/química , Ácido Fólico/química , Ácido Ascórbico , Polímeros , Pectinas
18.
Cureus ; 15(12): e49922, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38174175

RESUMO

BACKGROUND: Social media is a network that allows information to be shared globally with millions of users. It is becoming evident that social media plays quite a prominent role these days in skincare. Social media surely has come to benefit millions of its users around the globe, but the downside of social media is that it has the potential to put users at risk while they follow popular trends. AIM: This study aims to assess the impact of social media on choosing skincare and cosmetic products in Saudi Arabia with the most used social media platforms. METHODS: A questionnaire-based cross-sectional study was conducted targeting adult female residents across Saudi Arabia. Data were collected from the participants who met our criteria via electronic data collection Google forms did not show any nominative information that was distributed through social media platforms. The questionnaire covered participants' demographic data, social media use, source of information, and degree of trust with the influence of social media on using cosmetics. The eligible females were asked to fill out the study questionnaire received till no more new answers were obtained. RESULTS: A total of 1,174 females fulfilling the inclusion criteria completed the study questionnaire. Participants' ages ranged from 18 to more than 40 years with a mean age of 22.5 %C2%B1 13.9 years old. Exact of 655 (55.8%) were single, and 463 (39.4%) were married. The most used social media platforms included Snapchat (39.4%), TikTok (26.7%), and Instagram (19.6%). A total of 881 (75%) of the study females reported they use social media for more than an hour a day. Exact 51% of the study females became familiar with skin care products from social media platforms. Also, 91.3% of the study female's confidence in information related to cosmetic and skin care products was affected by visual presentation. CONCLUSION: In conclusion, the study showed that most of the study participants used social media for many hours daily mainly Snapchat, TikTok, and Instagram. Also, social media was the main source of information regarding skin care products mainly dermatologists on social media.

19.
Crit Rev Food Sci Nutr ; : 1-15, 2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36503314

RESUMO

Among various approaches to understand the health status of an individual, nutritional biomarkers can provide valuable information, particularly in terms of deficiencies, if any, and their severity. Commonly, the approach revolves around molecular sciences, and the information gained can support prognosis, diagnosis, remediation, and impact assessment of therapies. Microfluidic platforms can offer benefits of low sample and reagent requirements, low cost, high precision, and lower detection limits, with simplicity in handling and the provision for complete automation and integration with information and communication technologies (ICTs). While several advances are being made, this work details the underlying concepts, with emphasis on different point-of-care devices for the analysis of macro and micronutrient biomarkers. In addition, the scope of using different wearable microfluidic sensors for real-time and noninvasive determination of biomarkers is detailed. While several challenges remain, a strong focus is given on recent advances, presenting the state-of-the-art of this field. With more such biomarkers being discovered and commercialization-driven research, trends indicate the wide prospects of this advancing field in supporting clinicians, food technologists, nutritionists, and others.

20.
Dev Cell ; 57(20): 2350-2364.e7, 2022 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-36283390

RESUMO

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. During invasion, the encapsulating DCIS basement membrane (BM) is compromised, and tumor cells invade the surrounding stroma. The mechanisms that regulate functional epithelial BMs in vivo are poorly understood. Myosin-X (MYO10) is a filopodia-inducing protein associated with metastasis and poor clinical outcome in invasive breast cancer (IBC). We identify elevated MYO10 expression in human DCIS and IBC, and this suggests links with disease progression. MYO10 promotes filopodia formation and cell invasion in vitro and cancer-cell dissemination from progressively invasive human DCIS xenografts. However, MYO10-depleted xenografts are more invasive. These lesions exhibit compromised BMs, poorly defined borders, and increased cancer-cell dispersal and EMT-marker-positive cells. In addition, cancer spheroids are dependent on MYO10-filopodia to generate a near-continuous extracellular matrix boundary. Thus, MYO10 is protective in early-stage breast cancer, correlating with tumor-limiting BMs, and pro-invasive at later stages, facilitating cancer-cell dissemination.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Pseudópodes/metabolismo , Neoplasias da Mama/patologia , Miosinas/metabolismo , Membrana Basal/metabolismo , Carcinoma Ductal de Mama/metabolismo
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