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1.
Int J Pharm ; 654: 123999, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38490403

RESUMO

Colorectal cancer (CC) is one of the most predominant malignancies in the world, with the current treatment regimen consisting of surgery, radiation therapy, and chemotherapy. Chemotherapeutic drugs, such as 5-fluorouracil (5-FU), have gained popularity as first-line antineoplastic agents against CC but have several drawbacks, including variable absorption through the gastrointestinal tract, inconsistent liver metabolism, short half-life, toxicological reactions in several organ systems, and others. Therefore, herein, we develop chitosan-coated zinc-substituted cobalt ferrite nanoparticles (CZCFNPs) for the pH-sensitive (triggered by chitosan degradation within acidic organelles of cells) and sustained delivery of 5-FU in CC cells in vitro. Additionally, the developed nanoplatform served as an excellent exogenous optical coherence tomography (OCT) contrast agent, enabling a significant improvement in the OCT image contrast in a CC tissue phantom model with a biomimetic microvasculature. Further, this study opens up new possibilities for using OCT for the non-invasive monitoring and/or optimization of magnetic targeting capabilities, as well as real-time tracking of magnetic nanoparticle-based therapeutic platforms for biomedical applications. Overall, the current study demonstrates the development of a CZCFNP-based theranostic platform capable of serving as a reliable drug delivery system as well as a superior OCT exogenous contrast agent for tissue imaging.


Assuntos
Quitosana , Cobalto , Compostos Férricos , Nanopartículas , Medicina de Precisão , Meios de Contraste , Zinco , Tomografia de Coerência Óptica , Sistemas de Liberação de Medicamentos , Fluoruracila/uso terapêutico , Concentração de Íons de Hidrogênio , Nanomedicina Teranóstica
2.
Soft Matter ; 20(11): 2610-2623, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426537

RESUMO

Adhesive dynamics of cells plays a critical role in determining different biophysical processes orchestrating health and disease in living systems. While the rolling of cells on functionalised substrates having similarity with biophysical pathways appears to be extensively discussed in the literature, the effect of an external stimulus in the form of an electric field on the same remains underemphasized. Here, we bring out the interplay of fluid shear and electric field on the rolling dynamics of adhesive cells in biofunctionalised micro-confinements. Our experimental results portray that an electric field, even restricted to low strengths within the physiologically relevant regimes, can significantly influence the cell adhesion dynamics. We quantify the electric field-mediated adhesive dynamics of the cells in terms of two key parameters, namely, the voltage-altered rolling velocity and the frequency of adhesion. The effect of the directionality of the electric field with respect to the flow direction is also analysed by studying cellular migration with electrical effects acting both along and against the flow. Our experiment, on one hand, demonstrates the importance of collagen functionalisation in the adhesive dynamics of cells through micro channels, while on the other hand, it reveals how the presence of an axial electric field can lead to significant alteration in the kinetic rate of bond breakage, thereby modifying the degree of cell-substrate adhesion and quantifying in terms of the adhesion frequency of the cells. Proceeding further forward, we offer a simple theoretical explanation towards deriving the kinetics of cellular bonding in the presence of an electric field, which corroborates favourably with our experimental outcome. These findings are likely to offer fundamental insights into the possibilities of local control of cellular adhesion via electric field mediated interactions, bearing critical implications in a wide variety of medical conditions ranging from wound healing to cancer metastasis.


Assuntos
Adesivos , Sinais (Psicologia) , Adesão Celular , Fenômenos Biofísicos , Movimento Celular/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38083666

RESUMO

Optical coherence tomography (OCT) is a medical imaging modality that allows us to probe deeper sub-structures of skin. The state-of-the-art wound care prediction and monitoring methods are based on visual evaluation and focus on surface information. However, research studies have shown that sub-surface information of the wound is critical for understanding the wound healing progression. This work demonstrated the use of OCT as an effective imaging tool for objective and non-invasive assessments of wound severity, the potential for healing, and healing progress by measuring the optical characteristics of skin components. We have demonstrated the efficacy of OCT in studying wound healing progress in vivo small animal models. Automated analysis of OCT datasets poses multiple challenges, such as limitations in the training dataset size, variation in data distribution induced by uncertainties in sample quality and experiment conditions. We have employed a U-Net-based model for segmentation of skin layers based on OCT images and to study epithelial and regenerated tissue thickness wound closure dynamics and thus quantify the progression of wound healing. In the experimental evaluation of the OCT skin image datasets, we achieved the objective of skin layer segmentation with an average intersection over union (IOU) of 0.9234. The results have been corroborated using gold-standard histology images and co-validated using inputs from pathologists.Clinical Relevance-To monitor wound healing progression without disrupting the healing procedure by superficial, non-invasive means via the identification of pixel characteristics of individual layers.


Assuntos
Aprendizado Profundo , Tomografia de Coerência Óptica , Animais , Tomografia de Coerência Óptica/métodos , Pele/diagnóstico por imagem , Pele/patologia , Cicatrização , Fatores de Risco
4.
Nano Lett ; 23(15): 6845-6851, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37467358

RESUMO

Magnetic domain wall (DW)-based logic devices offer numerous opportunities for emerging electronics applications allowing superior performance characteristics such as fast motion, high density, and nonvolatility to process information. However, these devices rely on an external magnetic field, which limits their implementation; this is particularly problematic in large-scale applications. Multiferroic systems consisting of a piezoelectric substrate coupled with ferromagnets provide a potential solution that provides the possibility of controlling magnetization through an electric field via magnetoelastic coupling. Strain-induced magnetization anisotropy tilting can influence the DW motion in a controllable way. We demonstrate a method to perform all-electrical logic operations using such a system. Ferromagnetic coupling between neighboring magnetic domains induced by the electric-field-controlled strain has been exploited to promote noncollinear spin alignment, which is used for realizing essential building blocks, including DW generation, propagation, and pinning, in all implementations of Boolean logic, which will pave the way for scalable memory-in-logic applications.

5.
Macromol Biosci ; 23(10): e2300119, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37269219

RESUMO

While a sticking plasteris enough for healing of most of the minor cuts they may get routinely, critical situations like surgical, gunshot, accidental or diabetic wounds;lacarations and other cutaneous deep cuts may require implants and simultaneous medications for healing. From the biophysical standpoint, an internal force-based physical surface stimulusis crucial for cellular sensing during wound repair. In this paper, the authors report the fabrication of a porous, biomimmetically patterned silk fibroin scaffold loaded with ampicillin, which exhibits controlled release of the drug along with possible replenishment of the same. In vitro swelling study reveals that the scaffolds with hierarchical surface patterns exhibit lower swelling and degradation than other types of scaffolds. The scaffolds, that show remarkable broad-spectrum antibacterial efficacy, exhibit Korsemeyer-Peppas model for the ampicillin release patterns due to the structural hydrophobicity imparted by the patterns. Four distinct cell-matrix adhesion regimes are investigated for the fibroblasts to eventually form cell sheets all over the hierarchical surface structures. 4',6-diamidino-2-phenylindole (DAPI) and Fluorescein Diacetate (FDA) fluorescent staining clearly demonstrate the superiority of patterned surface over its other variants. A comparative immunofluorescence study among collagen I, vinculin, and vimentin expressions substantiated the patterned surface to be superior to others.

6.
J Biomed Mater Res A ; 111(5): 725-739, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36573698

RESUMO

Clinical success of regenerative medicine for treating deep-tissue skin injuries depends on the availability of skin grafts. Though bioengineered constructs are tested clinically, lack of neovascularization provide only superficial healing. Thus constructs, which promotes wound healing and supports vascularization has gained priority in tissue engineering. In this study, chitosan-collagen-fibrinogen (CCF) scaffold was fabricated using freeze-drying method without using any chemical crosslinkers. CCF scaffolds proved cytocompatibility and faster healing in in vitro scratch assay of primary human adult dermal fibroblasts cells with progressively increasing vascular endothelial growth factor-A and reducing vascular endothelial growth factor receptor 1 expressions. Skin regeneration evaluated on in vivo full thickness wound model confirmed faster remodeling with angiogenic signatures in CCF scaffold-implanted mice. Histopathological observations corroborated with stereo-zoom and SS-optical coherence tomography images of wound sites to prove the maturation of healing-bed, after 12 days of CCF implantation. Therefore, it is concluded that CCF scaffolds are promising for skin tissue regeneration and demonstrates pro-angiogenic potential.


Assuntos
Quitosana , Hemostáticos , Humanos , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular , Fibrinogênio , Tecidos Suporte , Pele/metabolismo , Colágeno/metabolismo , Neovascularização Patológica
7.
J Tissue Viability ; 31(4): 657-672, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35870995

RESUMO

We report synergism in scarless cutaneous wound repair by alginate hydrogel (HGSAG) embedded with an optimized blend of characterized Jamun honey and characterized indigenously prepared ghee. Thorough screening and characterization of honey and ghee are carried out followed by obtaining a novel dual crosslinking percolative gel casting fabrication method to come up with HGSAG showing superior chemical stability, and mechanical strength (Nanoindentation study; lowest stiffness: 0.71 ± 0.19 µN/nm), and surface morphology (SEM; highest roughness: 0.13 ± 0.04 µm) to other variants. In vitro swelling study and degradation behavior study show intermediate swelling (swelling index: 0.59 ± 0.008 in 98 h) and required restricted degradation (PBS: 73.38 ± 0.55%, DMEM: 83.48 ± 0.69% in 10 days) for HGSAG which is necessary for providing nutrients to cells and in vivo therapeutic efficacy. We observe the remarkable antibacterial efficacy of HGSAG against Staphylococcus mutans and Escherichia coli. This particular substrate also shows decent 3T3 fibroblasts viability, cell-cell communication followed by cell-matrix interaction, and proliferation compared to other variants. Molecular gene expression studies by quantitative RT-PCR technique reveal strong upregulation of collagen I, CD26, and TGF-ß3 while downregulation in the case of TGF-ß1 which eventually substantiates scarless wound healing potential of HGSAG. Wound closure kinetics is most rapidly and successfully underpinned by HGSAG while compared to other alternatives including marketed healing patches. Regular close monitoring using histopathological studies and real-time imaging by Swept-Source Optical Coherence Tomography of in vivo wound model treated with HGSAG come up with the fascinating result of scarless healing (HGSAG treated epithelial thickness: 62.96 ± 0.67 µm, unwounded akin epithelial thickness: 62.56 ± 0.34 µm) within 12 days of wounding. Thus, the work highlights modified and stabilized alginate hydrogel embedded with honey and ghee blend as a potential scarless full-thickness cutaneous wound healing bio-scaffold.


Assuntos
Ghee , Mel , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Alginatos/farmacologia , Alginatos/uso terapêutico , Alginatos/química , Cicatrização
8.
Langmuir ; 38(27): 8252-8265, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35758025

RESUMO

The incorrect metabolic breakdown of the nonaromatic amino acid methionine (Met) leads to the disorder called hypermethioninemia via an unknown mechanism. To understand the molecular level pathogenesis of this disorder, we prepared a DMPC lipid membrane, the mimicking setup of the cell membrane, and explored the effect of the millimolar level of Met on it. We found that Met forms toxic fibrillar aggregates that disrupt the rigidity of the membrane bilayer, and increases the dynamic response of water molecules surrounding the membrane as well as the heterogeneity of the membrane. Such aggregates strongly deform red blood cells. This opens the requirement to consider therapeutic antagonists either to resist or to inhibit the toxic amyloid aggregates against hypermethioninemia. Moreover, such disrupting effect on membrane bilayer and cytotoxicity along with deformation effect on RBC by the cross amyloids of Met and Phenylalanine (Phe) was found to be most virulent. This exclusive observation of the enhanced virulent effect of the cross amyloids is expected to be an informative asset to explain the coexistence of two amyloid disorders.


Assuntos
Aminoácidos , Metionina , Erros Inatos do Metabolismo dos Aminoácidos , Amiloide/química , Glicina N-Metiltransferase/deficiência , Metionina/química , Fenilalanina , Fosfolipídeos
9.
Proc Natl Acad Sci U S A ; 119(2)2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34983869

RESUMO

Precise information on localized variations in blood circulation holds the key for noninvasive diagnostics and therapeutic assessment of various forms of cancer. While thermal imaging by itself may provide significant insights on the combined implications of the relevant physiological parameters, viz. local blood perfusion and metabolic balance due to active tumors as well as the ambient conditions, knowledge of the tissue surface temperature alone may be somewhat inadequate in distinguishing between some ambiguous manifestations of precancer and cancerous lesions, resulting in compromise of the selectivity in detection. This, along with the lack of availability of a user-friendly and inexpensive portable device for thermal-image acquisition, blood perfusion mapping, and data integration acts as a deterrent against the emergence of an inexpensive, contact-free, and accurate in situ screening and diagnostic approach for cancer detection and management. Circumventing these constraints, here we report a portable noninvasive blood perfusion imager augmented with machine learning-based quantitative analytics for screening precancerous and cancerous traits in oral lesions, by probing the localized alterations in microcirculation. With a proven overall sensitivity >96.66% and specificity of 100% as compared to gold-standard biopsy-based tests, the method successfully classified oral cancer and precancer in a resource-limited clinical setting in a double-blinded patient trial and exhibited favorable predictive capabilities considering other complementary modes of medical image analysis as well. The method holds further potential to achieve contrast-free, accurate, and low-cost diagnosis of abnormal microvascular physiology and other clinically vulnerable conditions, when interpreted along with complementary clinically evidenced decision-making perspectives.


Assuntos
Diagnóstico por Imagem/métodos , Programas de Rastreamento/métodos , Neoplasias Bucais/diagnóstico por imagem , Perfusão/métodos , Adulto , Idoso de 80 Anos ou mais , Algoritmos , Biópsia , Diagnóstico por Imagem/instrumentação , Detecção Precoce de Câncer , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Masculino , Programas de Rastreamento/instrumentação , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Perfusão/instrumentação , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem
10.
Nanomedicine (Lond) ; 17(2): 107-132, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35000429

RESUMO

Rapid vascular growth, infiltrative cells and high tumor heterogenicity are some glioblastoma multiforme (GBM) characteristics, making it the most lethal form of brain cancer. Low efficacy of the conventional treatment modalities leads to rampant disease progression and a median survival of 15 months. Magnetic nanoparticles (MNPs), due to their unique physical features/inherent abilities, have emerged as a suitable theranostic platform for targeted GBM treatment. Thus, new strategies are being designed to enhance the efficiency of existing therapeutic techniques such as chemotherapy, radiotherapy, and so on, using MNPs. Herein, the limitations of the current therapeutic strategies, the role of MNPs in mitigating those inadequacies, recent advances in the MNP-based theranostics of GBM and possible future directions are discussed.


Lay abstract Glioblastoma multiforme is the most aggressive and deadly form of brain cancer. Currently available treatment methods such as chemotherapy, surgery and radiotherapy are not often successful. This leads to fast disease progression and a maximum survival of 15 months. Magnetic nanoparticles, due to their unique features, could be a suitable tool for treating and diagnosing glioblastoma. This review article discusses their potential in this field.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas de Magnetita , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Nanopartículas de Magnetita/uso terapêutico , Medicina de Precisão
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 268: 120676, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34890873

RESUMO

Diabetic retinopathy (DR) is a common health concern. Unfortunately, the metabolic pathway causing DR is yet to be understood. The carotenoid level in the human body is known to protect the health of the eyes. In this work, resonance Raman spectroscopy and multivariate analysis of the spectral data of human serum are reported as next-generation spectropathologic tools to detect retinal degeneration efficiently. The proposed technique shows promise by endorsing ocular carotenoids as a critical biomarker for such pathosis. Furthermore, the multivariate analysis of the spectral data distinguishes between two different stages of the disease. The machine learning algorithm is used to estimate a significant accuracy of 94% of the proposed model for the classification. As the carotenoid level can be controlled by dietary intake, we believe that the reported results also indicate a therapeutic role of the same in DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Algoritmos , Antioxidantes , Carotenoides , Retinopatia Diabética/diagnóstico , Humanos , Aprendizado de Máquina
12.
Med Mol Morphol ; 55(1): 20-26, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34482436

RESUMO

This paper focuses on the status of epithelial markers, E-cadherin, and p63 in the backdrop of an abnormal amount of collagen in the sub-mucosa of dysplastic and non-dysplastic grades of OSF. Histologically confirmed OSF and normal oral mucosa samples were procured. Samples were stained by Van Gieson's stain (VG) and immunohistochemistry. The captured images were analyzed by ImageJ software to quantify their grayscale intensities. There was a gradual increase in the intensity of VG stain from normal to non-dysplastic and dysplastic OSF and the differences in their mean grayscale values were found to be significant (p < 0.00001). The intensity of E-cadherin was found to be the highest in non-dysplastic conditions and lowest in dysplastic conditions. The intensity difference of E-cadherin between normal and non-dysplastic OSF was found to be significant (p < 0.00001). The grayscale scale intensity values for p63 in whole epithelium depicted significant differences between normal and diseased conditions but for its intensity, in basal cells, significant differences were found between non-dysplastic and other classes of tissues. There was a positive correlation observed between VG and p63 staining intensity. The diseased oral epithelium demonstrated greater deposition of sub-epithelial collagen fibers along with subsequent loss of E-cadherin and an increased p63 expression.


Assuntos
Fibrose Oral Submucosa , Antígenos CD , Caderinas/metabolismo , Colágeno/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Membrana , Mucosa Bucal/metabolismo , Fibrose Oral Submucosa/metabolismo , Fibrose Oral Submucosa/patologia
13.
Biomolecules ; 11(6)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203873

RESUMO

The choice of tissue fixation is critical for preserving the morphology and biochemical information of tissues. Fragile oral tissues with lower tensile strength are challenging to process for histological applications as they are prone to processing damage, such as tissue tear, wrinkling, and tissue fall-off from slides. This leads to loss of morphological information and unnecessary delay in experimentation. In this study, we have characterized the new PAXgene tissue fixation system on oral buccal mucosal tissue of cancerous and normal pathology for routine histological and immunohistochemical applications. We aimed to minimize the processing damage of tissues and improve the quality of histological experiments. We also examined the preservation of biomolecules by PAXgene fixation using FTIR microspectroscopy. Our results demonstrate that the PAXgene-fixed tissues showed significantly less tissue fall-off from slides. Hematoxylin and Eosin staining showed comparable morphology between formalin-fixed and PAXgene-fixed tissues. Good quality and slightly superior immunostaining for cancer-associated proteins p53 and CK5/6 were observed in PAXgene-fixed tissues without antigen retrieval than formalin-fixed tissues. Further, FTIR measurements revealed superior preservation of glycogen, fatty acids, and amide III protein secondary structures in PAXgene-fixed tissues. Overall, we present the first comprehensive evaluation of the PAXgene tissue fixation system in oral tissues. This study concludes that the PAXgene tissue fixation system can be applied to oral tissues to perform diagnostic molecular pathology experiments without compromising the quality of the morphology or biochemistry of biomolecules.


Assuntos
Neoplasias Bucais , Proteínas de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fixação de Tecidos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
14.
Int J Biol Macromol ; 185: 251-263, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34161821

RESUMO

The habit of chewing arecanut leads to fibrosis in the oral tissues, which can lead to cancer. Despite high mortality, fibrosis has limited clinical success owing to organ-specific variations, genetic predispositions, and slow progression. Fibrosis is a progressive condition that is unresponsive to medications in the severe phase. To understand underlying macromolecular changes we studied the extracellular matrix's (ECM) key molecular modifications in the early and late phase of arecanut-induced fibrosis in skin. To study the fibrosis, we topically applied arecanut extract on the mice skin. We observed that the matrix changes observe early and late phases based on ECM characteristics including the matrix proteins and the glycans. A spike in the levels of proteoglycans and ß-sheet structures are noted in the early phase. A significant drop in the proteoglycans and strengthening of amide covalent interactions is observed in the late phase. Although, almost no physical changes are noticeable only in the early phase; the late phase observes thick collagen bundling and a 4-fold stiffening of the skin tissue. The study indicates that the temporal interplay of proteins and glycans determine the matrix's severity state while opening avenues to research directed towards the phase-specific clinical discovery.


Assuntos
Areca/química , Matriz Extracelular/metabolismo , Extratos Vegetais/efeitos adversos , Pele/patologia , Células 3T3 , Amidas/metabolismo , Animais , Cromatografia Líquida , Colágeno/metabolismo , Matriz Extracelular/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Espectrometria de Massas , Camundongos , Proteoglicanas/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo
15.
Pneumonia (Nathan) ; 13(1): 8, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947476

RESUMO

BACKGROUND: Bacteria and respiratory viruses co-occur in the nasopharynx, and their interactions may impact pathogenesis of invasive disease. Associations of viruses and bacteria in the nasopharynx may be affected by HIV. METHODS: We conducted a nested case-control study from a larger cohort study of banked nasopharyngeal swabs from families with and without HIV in West Bengal India, to look at the association of viruses and bacteria in the nasopharynx of parents and children when they are asymptomatic. Quantitative polymerase chain reaction for 4 bacteria and 21 respiratory viruses was run on 92 random nasopharyngeal swabs from children--49 from children living with HIV (CLH) and 43 from HIV uninfected children (HUC)-- and 77 swabs from their parents (44 parents of CLH and 33 parents of HUC). RESULTS: Bacteria was found in 67% of children, viruses in 45%, and both in 27% of child samples. Staphylococcus aureus (53%) was the most common bacteria, followed by Streptococcus pneumoniae (pneumococcus) (37%) in children and parents (53, 20%). Regardless of HIV status, viruses were detected in higher numbers (44%) in children than their parents (30%) (p = 0.049), particularly rhinovirus (p = 0.02). Human rhinovirus was the most frequently found virus in both CLH and HUC. Children with adenovirus were at six times increased risk of also having pneumococcus (Odds ratio OR 6, 95% CI 1.12-31.9) regardless of HIV status. In addition, the presence of rhinovirus in children was associated with increased pneumococcal density (Regression coeff 4.5, 1.14-7.9). In CLH the presence of rhinovirus increased the risk of pneumococcal colonization by nearly sixteen times (OR 15.6, 1.66-146.4), and, pneumococcus and S. aureus dual colonization by nearly nine times (OR 8.7). CONCLUSIONS: Children more frequently carried viruses regardless of HIV status. In CLH the presence of rhinovirus, the most frequently detected virus, significantly increased co-colonization with pneumococcus and S. aureus.

16.
Protein J ; 40(5): 741-755, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33840009

RESUMO

Post-translational modifications (PTMs) impart structural heterogeneities that can alter plasma proteins' functions in various pathophysiological processes. However, the identification and mapping of PTMs in untargeted plasma proteomics is still a challenge due to the presence of diverse components in blood. Here, we report a label-free method for identifying and mapping hydroxylated proteins using tandem mass spectrometry (MS/MS) in the human plasma sample. Our untargeted proteomics approach led us to identify 676 de novo sequenced peptides in human plasma that correspond to 201 proteins, out of which 11 plasma proteins were found to be hydroxylated. Among these hydroxylated proteins, Immunoglobulin A1 (IgA1) heavy chain was found to be modified at residue 285 (Pro285 to Hyp285), which was further validated by MS/MS study. Molecular dynamics (MD) simulation analysis demonstrated that this proline hydroxylation in IgA1 caused both local and global structural changes. Overall, this study provides a comprehensive understanding of the protein profile containing Hyp PTMs in human plasma and shows the future perspective of identifying and discriminating Hyp PTM in the normal and the diseased proteomes.


Assuntos
Proteínas Sanguíneas , Hidroxiprolina , Processamento de Proteína Pós-Traducional , Proteoma , Proteômica , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Cromatografia Líquida , Humanos , Hidroxiprolina/análise , Hidroxiprolina/metabolismo , Proteoma/análise , Proteoma/metabolismo , Espectrometria de Massas em Tandem
18.
Eur J Cell Biol ; 100(1): 151146, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33418093

RESUMO

Oral sub-mucous fibrosis (OSF) is a pathophysiological state of oral cavity or oropharynx having a high chance of conversion to oral squamous cell carcinoma (OSCC). It involves fibrotic transformation of sub-epithelial matrix along with epithelial abnormalities. The present work aims to unveil the mechanistic domain regarding OSF to OSCC conversion exploring the scenario of hypoxia associated oxidative stress, epithelial-mesenchymal transition (EMT), metastasis and stemness acquisition. The study involves histopathological analysis of the diseased condition along with the exploration of oxidative stress status, assessment of mitochondrial condition, immunohistochemical analysis of HIF-1α, E-cadherin, vimentin, ERK, ALDH-1, CD133, Shh, Gli-1 and survivin expressions in the oral epithelial region together with the quantitative approach towards collagen deposition in the sub-epithelial matrix. Oxidative stress was found to be associated with type-II EMT in case of OSF attributing the development of sub-epithelial fibrosis and type-III EMT in case of OSCC favoring malignancy associated metastasis. Moreover, the acquisition of stemness during OSCC can also be correlated with EMT. Alteration of Shh and Gli-1 expression pattern revealed the mechanistic association of hypoxia with the phenotypic plasticity and disease manifestation in case of OSF as well as OSCC. Shh/ Gli-1 signaling can also be correlated with survivin mediated cytoprotective phenomenon under oxidative stress. Overall, the study established the correlative network of hypoxia associated oxidative stress, EMT and manifestation of oral pre-cancerous and cancerous condition in a holistic approach that may throw rays of hope in the therapeutic domain of the concerned diseases.


Assuntos
Carcinoma de Células Escamosas/fisiopatologia , Hipóxia Celular/fisiologia , Fibrose/fisiopatologia , Proteínas Hedgehog/metabolismo , Neoplasias Bucais/fisiopatologia , Transição Epitelial-Mesenquimal , Humanos , Estresse Oxidativo
19.
J Biophotonics ; 14(4): e202000357, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33332734

RESUMO

Imaging the structural modifications of underlying tissues is vital to monitor wound healing. Optical coherence tomography (OCT) images high-resolution sub-surface information, but suffers a loss of intensity with depth, limiting quantification. Hence correcting the attenuation loss is important. We performed swept source-OCT of full-thickness excision wounds for 300 days in mice skin. We used single-scatter attenuation models to determine and correct the attenuation loss in the images. The phantom studies established the correspondence of corrected-OCT intensity (reflectivity) with matrix density and hydration. We histologically validated the corrected-OCT and measured the wound healing rate. We noted two distinct phases of healing-rapid and steady-state. We also detected two compartments in normal scars using corrected OCT that otherwise were not visible in the OCT scans. The OCT reflectivity in the scar compartments corresponded to distinct cell populations, mechanical properties and composition. OCT reflectivity has potential applications in evaluating the therapeutic efficacy of healing and characterizing scars.


Assuntos
Cicatriz , Tomografia de Coerência Óptica , Animais , Cicatriz/diagnóstico por imagem , Camundongos , Pele/diagnóstico por imagem , Pele/patologia , Cicatrização
20.
IEEE J Biomed Health Inform ; 25(1): 152-162, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750913

RESUMO

Bright-field microscopy (BFM) encrypts the optical transillumination profile of the transmitted light attenuated by the complex micro-structural tissue convolutions, manifested by the dense and compact regions of the specimen under examination. The connotations of idiosyncratic tissue interaction dynamics with the onset of pre-cancerous activity are encoded in the BFM acquired oral mucosa histopathological images (OMHI). In the present study, our analysis is focused on the sub-epithelium region of the oral mucosa, which has high clinical significance but sparsely explored in the literature from the textural domain. Histopathology being the gold-standard technique till date, we have used the light microscopic histopathology images for tissue characterization. The tissue-index transmission patches (TITP) from the sub-epithelium region are cropped under the guidance of oral onco-pathologists. After that, the TITPs are characterized for its multi-scale spatial-deformation dynamics, while keeping the intrinsic anisotropic geometry, and local contour connectivity within tolerable limits. With recent studies exhibiting multifractal's potency in diverse biological system analysis, here, we exploit the 2D multifractal detrended fluctuation analysis (2D-MFDFA) on TITPs for exploring a discriminative set of multifractal signatures for healthy, oral potentially malignant disorders and oral cancer tissue sample. The predictive model's competency is validated on an experimentally collected corpus of TITP samples and substantiated via confirmatory data statistics and analysis, showing its inter-class segregation efficacy. Moreover, the 2D-MFDFA analysis evinces the complex multifractal patterns in TITPs, which is due to the presence of composite long-range correlations in the oral mucosa tissue fabric.


Assuntos
Mucosa Bucal , Neoplasias , Tecido Conjuntivo , Epitélio , Humanos , Microscopia
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