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1.
Anal Methods ; 16(16): 2533-2542, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38591099

RESUMEN

The development of paper-based devices has drawn a significant amount of attention, ranging from the creation of paper electronics to microfluidic devices. The flow of fluids through the paper substrate can be controlled by establishing a variety of barriers, which can be accomplished by either cutting or producing layers that are hydrophobic. Through the utilisation of this feature, a number of investigations, including mixing, modifying, and analytical studies, have been carried out on the paper substrate. However, because of the difficulties associated with its wettability, it is seldom investigated for the purpose of conducting evaporation studies of droplets. Traditionally, evaporation studies are carried out on a solid substrate like glass or silicon. Here we report a paper chip employing an impedance method to determine the characteristics of the droplet. It is also possible to determine the identity of the droplet by utilising the dielectric property of the liquid on a paper chip. A comparison is made between the traditional method of evaporation and the usage of the paper chip for the purpose of studying the evaporation of various liquids, ranging from ionic chemicals to volatile compounds. A subsequent step involves the utilisation of an electrical equivalent circuit in order to acquire the complex system attribute of the evaporation of the cellulose fibres. Finally, this reveals that paper chips have a significant amount of promise for use in scientific applications regarding evaporation analysis.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38687684

RESUMEN

Thorium (Th) and uranium (U) are important strategic resources in nuclear energy-based heavy industries such as energy and defense sectors that also generate significant radioactive waste in the process. The management of nuclear waste is therefore of paramount importance. Contamination of groundwater/surface water by Th/U is increasing at an alarming rate in certain geographical locations. This necessitates the development of strategic adsorbent materials with improved performance for capturing Th/U species from radioactive waste and groundwater. This report describes the design of a unique, robust, and radiation-resistant porous organic polymer (POP: TP-POP-SO3NH4), which demonstrates ultrafast removal of Th(IV) (<30 s)/U(VI) (<60 s) species present in simulated radioactive wastewater/groundwater samples. Thermal, chemical, and radiation stabilities of these POPs were studied in detail. The synthesized ammoniated POP revealed exceptional capture efficiency for trace-level Th (<4 ppb) and U (<3 ppb) metal ions through the cation-exchange mechanism. TP-POP-SO3NH4 shows a significant sorption capacity [Th (787 mg/g) and U (854 mg/g)] with an exceptionally high distribution coefficient (Kd) of 107 mL/g for Th. This work also demonstrates a facile protocol to convert a nonperforming POP, by simple chemical modifications, into a superfast adsorbent for efficient uptake/removal of U/Th.

3.
Soft Matter ; 20(11): 2610-2623, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38426537

RESUMEN

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.


Asunto(s)
Adhesivos , Señales (Psicología) , Adhesión Celular , Fenómenos Biofísicos , Movimiento Celular/fisiología
4.
Int J Pharm ; 654: 123999, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38490403

RESUMEN

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.


Asunto(s)
Quitosano , Cobalto , Compuestos Férricos , Nanopartículas , Medicina de Precisión , Medios de Contraste , Zinc , Tomografía de Coherencia Óptica , Sistemas de Liberación de Medicamentos , Fluorouracilo/uso terapéutico , Concentración de Iones de Hidrógeno , Nanomedicina Teranóstica
5.
Int J Biol Macromol ; 260(Pt 2): 129470, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38237817

RESUMEN

Polydimethylsiloxane (PDMS), even though widely used in microfluidic applications, its hydrophobic nature restricts its utility in some cases. To address this, PDMS may be used in conjunction with a hydrophilic material. Herein, the PDMS surface is modified by plasma treatment followed by cross-linking with the cataractous eye protein isolate (CEPI). CEPI-PDMS composites are prepared at three pH and the effects of CEPI on the chemical, physical, and electrical properties of PDMS are extensively investigated. The cross-linking between PDMS and the protein are confirmed by FTIR, and the contact angle measurements indicate the improved hydrophilic nature of the composite films as compared to PDMS. Atomic Force Microscopy results demonstrate that the surface roughness is enhanced by the incorporation of the protein and is a function of the pH. The effective elastic modulus of the composites is improved by the incorporation of protein into the PDMS matrix. Measurements of the dielectric properties of these composites indicate that they behave as capacitors at lower frequency range while demonstrating resistive characteristics at higher frequency. These composites provide preliminary ideas in developing flexible devices for potential applications in diverse areas such as energy storage materials, and thermo-elective wireless switching devices.


Asunto(s)
Dimetilpolisiloxanos , Microfluídica , Propiedades de Superficie , Dimetilpolisiloxanos/química , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas del Ojo
6.
Elife ; 132024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38289036

RESUMEN

Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These SrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of Srf knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases, SrfGFAP-ERCKO astrocytes abrogate nigral dopaminergic neuron death and reduce ß-amyloid plaques in mouse models of Parkinson's and Alzheimer's disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Astrocitos , Animales , Humanos , Ratones , Enfermedad de Alzheimer/metabolismo , Astrocitos/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Ratones Noqueados , Neuroprotección , Factor de Respuesta Sérica/metabolismo
7.
Int J Pharm ; 651: 123737, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38176480

RESUMEN

The progressive inflammatory disease atherosclerosis promotes myocardial infarction, stroke, and heart attack. Anti-inflammatory drugs treat severe atherosclerosis. They are inadequate bioavailability and cause adverse effects at higher doses. A new nanomaterial coupled pH-apperceptive drug delivery system for atherosclerotic plaque is outlined here. We have synthesized a Graphene Oxide-Gelatin-Atorvastatin (GO-Gel-ATR) nanodrug characterized by spectroscopic and imaging techniques. The encapsulation efficiency of GO-Gel-ATR (79.2%) in the loading process is observed to be better than GO-ATR (66.8%). The internal milieu of the plaque cells has a pH of 6.8. The GO-Gel-ATR displays sustained and cumulative release profile at pH 6.8 compared to ATR and GO-ATR. Our proposed nanocomposite demonstrated high cytocompatibility up to 100µg/mL in foam cells induced by Oxidized-Low Density Lipoprotein (Ox-LDL) and Lipopolysaccharides (LPS) compared to normal macrophages for 24 and 48 h. The uptake efficacy of the nanodrugs is shown to be enhanced in foam cells compared to normal macrophage. Oil red O staining of foam cells with and without drugs confirmed therapeutic efficacy. Foam cells treated with nanocomposite had more lipids efflux than ATR. The finding of the in-vitro study reveals that the GO-Gel-ATR nanocomposite carriers have the potential to deliver anti-atherosclerotic drugs effectively and inhibit atherosclerotic plaque progression.


Asunto(s)
Aterosclerosis , Grafito , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Gelatina , Preparaciones Farmacéuticas , Aterosclerosis/tratamiento farmacológico , Lipoproteínas LDL , Concentración de Iones de Hidrógeno
8.
Int J Biol Macromol ; 256(Pt 2): 128271, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38000604

RESUMEN

The dynamic equilibrium between an array of molecular forces precisely organizes the native structure of the protein. The charge on the protein, an interconnected network continuum, is crucial in determining its secondary and tertiary structure. The photolysis of the protein by ultraviolet (UV) light occurs by generating reactive oxygen intermediates from the interaction of matter and light. Herein, we have investigated the photolysis of the protein and its prevention by the pre-treatment with silver nanoparticle (AgNP) using non-faradaic electrical impedance spectroscopy (Nf-EIS). Five microliters of protein solution are used to measure its impedimetric parameters via Nf-EIS. The photoionization process sparks off an altered surface charge continuum of the protein molecules in tandem with the genesis of solvated electrons and protons, spurring an upward shift in conductivity. The AgNP pre-treatment has reduced the damaging effects of the UV radiation, which is reflected as lesser conductivity in contrast to the photolyzed protein solution. Raman Spectroscopy and circular dichroism tests affirm the trend of Nf-EIS results. These results show that Nf-EIS can evaluate protein structure analysis utilized in quality assurance and toxicity analysis for biologics.


Asunto(s)
Nanopartículas del Metal , Plata , Plata/química , Nanopartículas del Metal/química , Fotólisis , Impedancia Eléctrica , Rayos Ultravioleta
9.
Indian J Surg Oncol ; 14(3): 752-754, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37900645

RESUMEN

Background: Ewing sarcoma is a malignancy that commonly affects the skeletal system and primary extraskeletal involvement is rare. Extraskeletal Ewing sarcoma (EES) arises in soft tissue anywhere in the body. These are very rarely seen aggressive tumours. There have been only 7 reported cases of EES of penis. Case Presentation: We report a 22-year-young patient who presented to our hospital with a ulcero-proliferative growth in the shaft of penis. There were no other complaints indicating any metastasis. Incisional biopsy was suggestive of invasive malignancy. He was scheduled for a partial penectomy. Final HPE and IHC were suggestive of EES. Conclusion: EES as a subtype of Ewing sarcoma is rare and it can occur in any soft tissue site. Hence, clinicians need to differentiate this entity from other soft tissue sarcomas. Early diagnosis and timely treatment of EES are pivotal for a favourable prognosis due to its aggressive nature. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01793-x.

10.
Ann Pediatr Cardiol ; 16(2): 127-130, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767178

RESUMEN

COVID-19 infection has myriad manifestations from self-limiting illness to stormy multi-organ failure. A 28-year-old woman negative for COVID reverse transcription-polymerase chain reaction underwent an uneventful elective device closure of atrial septal defect on intubation anesthesia. While a brief postprocedural endotracheal bleed was noted, significant hypoxia and respiratory distress ensued after extubation with biventricular dysfunction, pleural effusion, and radiographic evidence of acute respiratory distress syndrome. COVID antibodies were positive, and inflammatory markers were elevated. After a conservative multipronged medical management including anticoagulation, antibiotics, aspirin, beta-blocker, diuretics, and sildenafil, she improved in 1 week. The clinical course during this pandemic era gives a possibility of a post-COVID inflammatory syndrome as a potential etiology.

11.
ACS Appl Mater Interfaces ; 15(36): 43060-43074, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37643137

RESUMEN

The sensing behavior of a MoS2-functionalized paper sensor towards dopamine was explored through a combinatorial approach of theoretical analysis, subsequent experimental validation, and machine-learning-driven predictive modeling of the measured electrochemical outputs. The suitability of the chosen 2D material for efficient detection of dopamine was confirmed using density functional theory. The physisorption behavior along with electrostatic interaction due to the incorporation of dopamine on MoS2 was unraveled under the purview of theoretically estimated noncovalent interaction and charge density difference plot. The theoretical Löwdin population analysis elucidates the alteration in oxidation potential of dopamine, as observed in electrochemical experiments. The electrochemical responses of the developed sensor with the spiked serum samples showed an average accuracy of more than 96% with a limit of detection of 10 nM. Furthermore, implementation of a machine-intelligent interactive web app interface improved the resolution of the sensing platform significantly with an enhanced accuracy of nearly 99%.


Asunto(s)
Dopamina , Aplicaciones Móviles , Molibdeno , Inteligencia Artificial , Aprendizaje Automático
12.
Anal Methods ; 15(29): 3532-3542, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37435749

RESUMEN

The blood hematocrit (Hct) level provides vital information about a person's health. Traditional Hct measurement equipment relies heavily on infrastructure and skilled manpower, limiting its broad implementation in resource-limited contexts. Therefore, we developed a simple, reagent-free, non-destructive, smartphone-integrated paper-based device for Hct measurement by analyzing blood-spreading area on a paper substrate. Blood spreading area was found to be dependent on the Hct value, paper properties, and assay duration. This device was calibrated using a custom-made Python algorithm with 10 µl of blood, which produced a sensitivity of -1.90 ± 0.03 mm2/Hct (%) with a LOD as low as 2.17% Hct. The device linear range (8.8 to 58% Hct) is wide enough to cover the clinically relevant range of blood Hct (%). Furthermore, this Python algorithm was coupled with a user-friendly and clinically beneficial Android application (app) to establish an automated tool for quantitative estimation. Comparing the app performance with the result obtained from the gold standard hematology analyzer using blood from 87 subjects reveals a strong correlation (r = 0.99), an average bias of 0.15 with limits of agreement of -2.5 to 2.79 at 95% CI. The device exhibits an accuracy of 96.85% and acceptable reproducibility, with CV ranging from 0.8 to 7.5%. An integrated detection cum readout guiding pattern may allow this device to be suitable for simultaneous quantitative and qualitative estimation and to be employed in both developed and resource-limited clinical settings for Hct measurement in routine checkups and regular monitoring during critical care, as well as in the initial screening of large anemic populations.


Asunto(s)
Pruebas con Sangre Seca , Teléfono Inteligente , Humanos , Hematócrito , Reproducibilidad de los Resultados , Algoritmos
13.
Biomacromolecules ; 24(5): 2003-2008, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-37126604

RESUMEN

The therapeutic value of delivering recombinant uricase to human patients has been appreciated for decades. The development of therapeutic uricases has been hampered by the fact that humans do not encode an endogenous uricase and therefore most recombinant forms of the protein are recognized as foreign by the immune system and are therefore highly immunogenic. In order to both shield and stabilize the active enzyme, we encapsulated a functional ancestral uricase in recombinant, noninfectious Qß capsid nanoparticles and characterized its catalytic activity. Oral delivery of the nanoparticles moderated key symptoms of kidney dysfunction in uricase-knockout mice by lowering uric acid levels. Histological kidney samples of the treated mice suggest that delivery of recombinant uricase had a protective effect against the destructive effects of uric acid that lead to renal failure caused by hyperuricemia.


Asunto(s)
Hiperuricemia , Nanopartículas , Humanos , Ratones , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/genética , Ácido Úrico , Urato Oxidasa/genética , Ratones Noqueados
14.
J Colloid Interface Sci ; 640: 246-260, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36863181

RESUMEN

A liquid filament may pinch off into different shapes on interacting with a soft surface, as modulated by the interplay of inertial, capillary, and viscous forces. While similar shape transitions may intuitively be realized for more complex materials such as soft gel filaments as well, their intricate controllability towards deriving precise and stable morphological features remains challenging, as attributed to the complexities stemming from the underlying interfacial interactions over the relevant length and time scales during the sol-gel transition process. Circumventing these deficits in the reported literature, here we report a new means of precisely-controlled fabrication of gel microbeads via exploiting thermally-modulated instabilities of a soft filament atop a hydrophobic substrate. Our experiments reveal that abrupt morphological transitions of the gel material set in at a threshold temperature, resulting in spontaneous capillary thinning and filament breakup. We show that this phenomenon may be precisely modulated by an alteration in the hydration state of the gel material that may be preferentially dictated by its intrinsic glycerol content. Our results demonstrate that the consequent morphological transitions give rise to topologically-selective microbeads as an exclusive signature of the interfacial interactions of the gel material with the deformable hydrophobic interface underneath. Thus, intricate control may be imposed on the spatio-temporal evolution of the deforming gel, facilitating the inception of highly ordered structures of specific shapes and dimensionalities on demand. This is likely to advance the strategies of long shelf-life analytical biomaterial encapsulations via realizing one-step physical immobilization of bio-analytes on the bead surfaces as a new route to controlled materials processing, without demanding any resourced microfabrication facility or delicate consumable materials.

15.
Appl Radiat Isot ; 196: 110725, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36878089

RESUMEN

The present article describes the development of robust lyophilized kit for convenient formulation of [68Ga]Ga-DOTA-E-[c(RGDfK)]2 (E = glutamic acid, R = arginine, G = glycine, D = aspartic acid, f = phenylalanine, K = lysine) radiopharmaceutical for clinical use in non-invasive monitoring of malignancies overexpressing integrin αvß3 receptors. Five batches of the kit were prepared with optimized kit contents, all of which showed high 68Ga-radiolabeling yield (>98%). Pre-clinical evaluation of the [68Ga]Ga-radiotracer in SCID mice bearing FTC133 tumour exhibited significant accumulation in the tumor xenograft. Preliminary human clinical investigation carried out in a 60 year old male patient with metastatic lung cancer revealed high radiotracer uptake in the tumor along with satisfactory target to non-target contrast. The developed kit formulation also showed a long shelf-life of at least 12 months on storage at 0 °C. All these results point towards the promising attributes of the developed kit formulation for convenient preparation of [68Ga]Ga-DOTA-E-[c(RGDfK)]2 for routine clinical use.


Asunto(s)
Radioisótopos de Galio , Tomografía de Emisión de Positrones , Masculino , Ratones , Animales , Humanos , Persona de Mediana Edad , Ratones SCID , Tomografía de Emisión de Positrones/métodos , Compuestos Heterocíclicos con 1 Anillo , Línea Celular Tumoral
16.
Biomacromolecules ; 24(4): 1934-1941, 2023 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-36988581

RESUMEN

Enzyme activity requires sequential binding and chemical transformation of substrates. While directed evolution and random mutagenesis are common methods for improving catalytic activity, these methods do not allow for independent control of KM and kcat. To achieve such control, we envisioned that the colocalization of aptamers and enzymes that act on the same molecule could increase catalytic efficiency through preconcentration of substrate. We explored this concept with cocaine esterase and anticocaine aptamers having varying KD values, both encapsulated in MS2 virus-like particles. Rate enhancements were observed with magnitudes dependent on both aptamer:enzyme stoichiometry and aptamer KD, peaking when aptamer KD and enzyme KM were roughly equivalent. This beneficial effect was lost when either aptamer binding was too tight or the aptamers were not constrained to be close to the catalyst. This work demonstrates a modular way to enhance catalysis by independently controlling substrate capture and release to the processing enzyme.


Asunto(s)
Aptámeros de Nucleótidos , Catálisis , Aptámeros de Nucleótidos/química , Cinética
17.
Bioorg Med Chem Lett ; 86: 129240, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36931350

RESUMEN

Folate receptors (FRs) are known to be over-expressed in several human malignancies and therefore serve as an important target for small radiolabeled folate derivatives for non-invasive imaging of tumor, which is an important tool for future treatment recourse. In the present article, we report the synthesis of a new 99mTc-labeled radiotracer for the aforementioned application following the well-established 99mTc-'4+1' chemistry. Formation of the desired [99mTc]Tc-complex with >95% radiochemical purity was confirmed by radio-HPLC and its structure was ascertained by characterizing a natural rhenium analogue of the said complex. Although the ligand exhibited a weaker affinity towards FRs compared to native folic acid (IC50 8.09 µM vs 29.46 nM), the 99mTc-labeled complex was found to bind folate receptor-positive KB cells with high specificity (∼90%). Similar studies in a folate receptor negative cell line viz. A549 further corroborated the receptor-specificity of the synthesized complex. In vivo studies in KB tumor xenograft showed moderate uptake of ∼2.6% upto 3 h post-injection with high specificity (∼80%). The favorable features observed warrant further screening of the current design towards achieving an improved molecular probe for the said application.


Asunto(s)
Ácido Fólico , Neoplasias , Humanos , Receptores de Folato Anclados a GPI/metabolismo , Ácido Fólico/química , Radiofármacos , Proteínas Portadoras/metabolismo , Tecnecio/química
18.
Front Cell Dev Biol ; 11: 1032504, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36819109

RESUMEN

Neurons in the mammalian brain exhibit enormous structural and functional diversity across different brain regions. Compared to our understanding of the morphological diversity of neurons, very little is known about the heterogeneity of neuronal nuclear morphology and how nuclear size changes in aging and diseased brains. Here, we report that the neuronal cell nucleus displays differences in area, perimeter, and circularity across different anatomical regions in the mouse brain. The pyramidal neurons of the hippocampal CA3 region exhibited the largest area whereas the striatal neuronal nuclei were the smallest. These nuclear size parameters also exhibited dichotomous changes with age across brain regions-while the neocortical and striatal neurons showed a decrease in nuclear area and perimeter, the CA3 neurons showed an increase with age. The nucleus of parvalbumin- and calbindin-positive interneurons had comparable morphological features but exhibited differences between brain regions. In the context of activity-dependent transcription in response to a novel environment, there was a decrease in nuclear size and circularity in c-Fos expressing neurons in the somatosensory cortex and hippocampal CA1 and CA3. In an APP/PS1 mutant mouse model of Alzheimer's disease (AD), the neuronal nuclear morphology varies with plaque size and with increasing distance from the plaque. The neuronal nuclear morphology in the immediate vicinity of the plaque was independent of the plaque size and the morphology tends to change away from the plaque. These changes in the neuronal nuclear size and shape at different ages and in AD may be attributed to changes in transcriptional activity. This study provides a detailed report on the differences that exist between neurons in nuclear morphology and can serve as a basis for future studies.

19.
Exp Cell Res ; 424(1): 113488, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36736226

RESUMEN

Glioma is difficult-to-treat because of its infiltrative nature and the presence of the blood-brain barrier. Temozolomide is the only FDA-approved drug for its management. Therefore, finding a novel chemotherapeutic agent for glioma is of utmost importance. Magnolol, a neolignan, has been known for its apoptotic role in glioma. In this work, we have explored a novel anti-glioma mechanism of Magnolol associated with its role in autophagy modulation. We found increased expression levels of Beclin-1, Atg5-Atg12, and LC3-II and lower p62 expression in Magnolol-treated glioma cells. PI3K/AKT/mTOR pathway proteins were also downregulated in Magnolol-treated glioma cells. Next, we treated the glioma cells with Insulin, a stimulator of PI3K/AKT/mTOR signaling, to confirm that Magnolol induced autophagy by inhibiting this pathway. Insulin reversed the effect on Magnolol-mediated autophagy induction. We also established the same in in vivo glioma model where Magnolol showed an anti-glioma effect by inducing autophagy. To confirm the cytotoxic effect of Magnolol-induced autophagy, we used Chloroquine, a late-stage autophagy inhibitor. Chloroquine efficiently reversed the anti-glioma effects of Magnolol both in vitro and in vivo. Our study revealed the cytotoxic effect of Magnolol-induced autophagy in glioma, which was not previously reported. Additionally, Magnolol showed no toxicity in non-cancerous cell lines as well as rat organs. Thus, we concluded that Magnolol is an excellent candidate for developing new therapeutic strategies for glioma management.


Asunto(s)
Antineoplásicos , Glioma , Insulinas , Lignanos , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Antineoplásicos/farmacología , Lignanos/farmacología , Lignanos/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/metabolismo , Autofagia , Cloroquina/farmacología , Cloroquina/uso terapéutico , Insulinas/farmacología , Insulinas/uso terapéutico , Línea Celular Tumoral , Apoptosis
20.
Lab Chip ; 23(2): 318-329, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36562505

RESUMEN

We report a highly accurate single-step label-free testing technology for simultaneous and independent hematocrit (Hct) and hemoglobin (Hb) level detection from a drop of whole blood by employing a disposable paper strip sensor interfaced with a portable impedimetric device. The paper strip is fabricated by in situ automated printing of a customized electrode template on the non-glossy side of a commercially available photo paper substrate followed by graphite deposition. The integrated platform device technology additionally includes a compact detection cum readout unit comprising a high precision impedance converter system that combines an on-board frequency generator with an analog-to-digital converter evaluation board, collectively interfaced with a central processor, calibration circuit, and smartphone. Employing a dispensed blood sample volume of 25 µL, the device is shown to have a sensitivity of 92 Ω/Hct and 287 Ω/Hb at an optimal frequency of 57 kHz. The respective linear response regimes appear to be wide enough to cover physiologically relevant limits, with excellent stability and reproducibility. Validation with clinical samples reveals limits of detection of Hct and Hb levels as low as 4.66% and 1.89 g dL-1, respectively, which are beyond the quantitative capability of commonly used affordable point of care test kits. The envisaged paradigm of rapid, robust, highly accurate, energy-efficient, simple, user-friendly, multiplex portable detection, obviating any possible ambiguities in interpretation due to common artefacts of colorimetric detection technologies such as optical interference with the image analytical procedure due to the inherent redness of blood samples and background illumination, renders this ideal for deployment in resource-limited settings.


Asunto(s)
Hemoglobinas , Teléfono Inteligente , Hematócrito , Reproducibilidad de los Resultados , Hemoglobinas/análisis , Pruebas en el Punto de Atención
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