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1.
Am J Pathol ; 194(4): 510-524, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38171450

RESUMO

Despite significant advances in medical treatments and drug development, atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death worldwide. Dysregulated lipid metabolism is a well-established driver of ASCVD. Unfortunately, even with potent lipid-lowering therapies, ASCVD-related deaths have continued to increase over the past decade, highlighting an incomplete understanding of the underlying risk factors and mechanisms of ASCVD. Accumulating evidence over the past decades indicates a correlation between amino acids and disease state. This review explores the emerging role of amino acid metabolism in ASCVD, uncovering novel potential biomarkers, causative factors, and therapeutic targets. Specifically, the significance of arginine and its related metabolites, homoarginine and polyamines, branched-chain amino acids, glycine, and aromatic amino acids, in ASCVD are discussed. These amino acids and their metabolites have been implicated in various processes characteristic of ASCVD, including impaired lipid metabolism, endothelial dysfunction, increased inflammatory response, and necrotic core development. Understanding the complex interplay between dysregulated amino acid metabolism and ASCVD provides new insights that may lead to the development of novel diagnostic and therapeutic approaches. Although further research is needed to uncover the precise mechanisms involved, it is evident that amino acid metabolism plays a role in ASCVD.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Fatores de Risco , Biomarcadores , Aminoácidos/uso terapêutico
2.
FASEB J ; 37(8): e23105, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37490000

RESUMO

Hepatocellular carcinoma (HCC) is one of the most fatal and fastest growing malignancies. Recently, nonalcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20-type kinases, MST3 and MST4, have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC. By analyzing public datasets and in-house cohorts, we found that hepatic MST3 and MST4 expression was positively correlated with the incidence and severity of HCC. We also found that the silencing of both MST3 and MST4, but also either of them individually, markedly suppressed the tumorigenesis of human HCC cells including attenuated proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3/MST4-deficient hepatocytes and identified GOLGA2 and STRIPAK complex as the binding partners of both MST3 and MST4. These findings reveal that MST3 and MST4 play a critical role in promoting the progression of HCC and suggest that targeting these kinases may provide a novel strategy for the treatment of liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Biópsia , Técnicas de Cultura de Células
3.
Langmuir ; 40(17): 8820-8826, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38619546

RESUMO

Hollow porous organic capsules (HPOCs) with an entrapped active catalyst have nanosized cavities, providing the benefits of a nanoreactor, as well as separation of the catalysts from the reaction medium via pores acting as a size-exclusion gate. Such purpose-built HPOCs with desired molecular weight cutoffs offer the advantages of semipermeable membrane separation and a sustainable chemical process that excludes energy-extensive separation. Here, we report a newly synthesized HPOC with an entrapped Pd(PPh3)2Cl2 as the catalyst for demonstrating a Suzuki-Miyaura coupling reaction as a proof of concept.

4.
Langmuir ; 40(18): 9481-9489, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38650463

RESUMO

Herein, we have isolated onion-like nanocarbon (ONC) from the exhaust soot of diesel engines and further doped it with nitrogen (N) and sulfur (S) to fabricate N,S-co-doped ONC (N-S-ONC). To explore its application feasibility, we have assembled an aqueous Zn-ion hybrid supercapacitor (ZIHSC) with a N-S-ONC cathode, which attains high specific capacitance with good rate capability. In-depth analyses suggest that the mechanism of charge storage in the ONC is governed by both capacitive-controlled and diffusion-controlled processes, with the capacitive processes leading at all sweep rates. The ZIHSC demonstrated a good energy density of 50 Wh/kg, a maximum power density of 3.6 kW/kg, and an impressive cycle life with 73% capacitance retention after 50,000 charge-discharge cycles. The study suggests the potential possibly for the long-term application of BC derived nanocarbon in electrochemical energy storage systems (EESSs).

5.
Langmuir ; 40(19): 9855-9872, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38687994

RESUMO

Two-dimensional (2D) layered materials like graphene, transition-metal dichalcogenides (TMDs), boron nitrides, etc., exhibit unique and fascinating properties, such as high surface-to-volume ratio, inherent mechanical flexibility and robustness, tunable bandgap, and high carrier mobility, which makes them an apt candidate for flexible electronics with low consumption of power. Because of these properties, they are in tremendous demand for advancement in energy, environmental, and biomedical sectors developed through various technologies. The production and scalability of these materials must be sustainable and ecofriendly to utilize these unique properties in the real world. Here, in this current review, we review molybdenum disulfide (MoS2 nanosheets) in detail, focusing on exfoliated MoS2 in water and the applicability of aqueous MoS2 suspensions in various fields. The exfoliation of MoS2 results in the formation of single or few-layered MoS2. Therefore, this Review focuses on the few layers of exfoliated MoS2 that have the additional properties of 2D layered materials and higher excellent compatibility for integration than existing conventional Si tools. Hence, a few layers of exfoliated MoS2 are widely explored in biosensing, gas sensing, catalysis, photodetectors, energy storage devices, a light-emitting diode (LED), adsorption, etc. This review covers the numerous methodologies to exfoliate MoS2, focusing on the various published methodologies to obtain nanosheets of MoS2 from water solutions and their use.

6.
Inorg Chem ; 63(24): 11102-11112, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38831586

RESUMO

Binuclear vanadyl(IV) porphyrin (V2BP), where two vanadium(IV) porphyrin macrocycles are linked through benzimidazole units at the ß-positions, has been prepared and characterized with various techniques, such as UV-vis, Fourier transform-infrared, electron paramagnetic resonance, cyclic voltammetry, density functional transform calculations, and mass spectrometry. V2BP exhibits a red shift (Δλmax = 10 nm) in the Soret band as compared with unsubstituted parent vanadyl(IV) meso-tetraphenylporphyrin (VP). The synthesized binuclear vanadyl(IV) porphyrin (V2BP) has further been studied as a catalyst to explore a single-pot multicomponent Biginelli reaction producing biologically active 3,4-dihydropyrimidin-2-(1H)-one (DHPM)-based biomolecules and the corresponding thiones under solvent-free conditions and its catalytic activity has been compared with vanadyl(IV) meso-tetraphenylporphyrin (VP). Several reaction conditions, such as the amount of catalyst, time, solvent, and temperature, have been optimized to obtain the maximum yield of DHPMs or thiones. The synthesized ß-functionalized V2BP porphyrin dimer manifests much higher conversion (84-95% yield) of DHPMs or the corresponding thiones under the optimized reaction conditions with high TON (4454-5037) and TOF (1113-1259 h-1) values for the one-pot multicomponent Biginelli reaction as compared to the literature. The catalyst exhibited excellent recyclability up to 10 cycles.

7.
Headache ; 64(7): 810-824, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38785386

RESUMO

OBJECTIVE: To evaluate the real-world effectiveness of eptinezumab for migraine prevention in Asian patients. BACKGROUND: Eptinezumab is a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), a potent vasodilator with an important role in migraine pathophysiology. Although there is robust clinical evidence from pivotal Phase 3 placebo-controlled trials of the efficacy of eptinezumab for migraine prevention, there are limited data on the real-world effectiveness of eptinezumab in Asian patient cohorts. METHODS: This was a non-interventional, prospective, multisite cohort study of adults with migraine (International Classification of Headache Disorders, 3rd edition criteria) in Singapore who were prescribed eptinezumab (100 mg at baseline and Month 3, administered intravenously) and were followed until Month 6. The primary endpoint was change from baseline in monthly migraine days (MMDs) at Month 3 and Month 6. Secondary endpoints were ≥30% and ≥50% responder rates, and change from baseline in the Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Migraine-Specific Quality of Life (MSQ), patient-identified most bothersome symptom (PI-MBS), acute medication use at Month 3 and Month 6, and safety. RESULTS: Enrolled patients (completed = 29/30) had on average 3.4 (SD 2.9) previous preventive treatments; 29/30 of the patients had trialed at least one previous preventive treatment without benefit. Most had previously trialed oral preventives (87%, 26/30) and anti-CGRP (70%, 21/30). Relative to baseline, mean MMDs decreased by 4.3 days (95% CI 2.1-6.4; p < 0.001) at Month 3 and 4.9 days (95% CI 2.1-7.7; p < 0.001) at Month 6. At Month 3 and Month 6, 14/30 (47%) and 15/29 (52%) of the patients were ≥30% responders, and 6/30 (20%) and 8/29 (28%) patients were ≥50% responders, respectively. The number of patients with severe life impairment based on the HIT-6 score (total score 60-78) decreased from 24/30 (80%) at baseline to 19/30 (63%) at Month 3 and 19/29 (66%) at Month 6. The mean MIDAS score decreased by 24.6 points (95% CI 2.82-46.38; p = 0.028) at Month 6, and the mean MSQ score increased by 12.2 points (95% CI 5.18-19.20; p = 0.001) at Month 3 and 13.6 points (95% CI 4.58-22.66; p = 0.004) at Month 6. Most patients reported improvement in the PI-MBS at Month 3 (73%, 22/30) and Month 6 (55%, 16/29). Acute medication use for headache relief decreased by 3.3 days/month (95% CI 1.0-5.6; p = 0.007) at Month 3 and 4.7 days/month (95% CI 1.7-7.7; p = 0.003) at Month 6. Treatment-emergent adverse events (TEAEs) were reported in 16/30 (54%) patients, mostly mild/moderate in severity. No serious TEAEs led to treatment discontinuation. CONCLUSION: Quarterly eptinezumab administration was effective and well-tolerated in Asian patients with chronic migraine.


Assuntos
Anticorpos Monoclonais Humanizados , Povo Asiático , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Masculino , Feminino , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos Prospectivos , Pessoa de Meia-Idade , Singapura , Povo Asiático/etnologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/administração & dosagem , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Qualidade de Vida , Resultado do Tratamento
8.
Phys Chem Chem Phys ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39036903

RESUMO

This study describes a numerical analysis on blue energy generation using a charged nanochannel with an integrated pH-sensitive polyelectrolyte layer (PEL), considering ion partitioning effects due to permittivity differences. The mathematical model for ionic and fluidic transport is solved using the finite element method, and the model validation is performed against existing theoretical and experimental results. The study investigates the influence of electrolyte concentration, permittivity ratio, and salt types (KCl, BeCl2, AlCl3) on the energy conversion process. The findings illustrate the substantial role of ion partitioning in modulating ionic concentration and potential fields, thereby affecting current profiles and energy conversion efficiencies. Remarkably, overlooking ion partitioning leads to significant overestimations of power density, highlighting the necessity of this consideration for accurate device performance predictions. This work introduces a promising configuration that achieves higher power densities, paving the way for the next generation of efficient energy-harvesting devices. The findings offer valuable insights into the development of state-of-the-art blue energy harvesting nanofluidic devices, advancing sustainable energy production.

9.
Environ Res ; 252(Pt 3): 118979, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38685303

RESUMO

Shark is a seafood commodity that is a good source of minerals and accumulates heavy metals and trace elements through biomagnification, which can pose health risk if taken above the permissible limit. A study was conducted on commonly landed eleven shark species (Scoliodon laticaudus, Rhizopriodon oligolinx, Sphyrna lewini (CR), Carcharhinus macloti, Carcharinus limbatus, Carcharhinus amblyrhynchoides, Carcharhinus sorrah, Carcharinus falciformes(VU), Glaucostegus granulatus, Chiloscyllium arabicum, Loxodon macrorhinus) and analyzed for their heavy metal content, Hazard Index, Total Hazard Quotient, Metal Pollution Index, and also calculated the health risk associated with the consumption. Most of the heavy metals and trace minerals were found to be within the acceptable limit. The Targeted Hazard Quotient (THQ) and the Hazard Index (HI) of all the species except two were less than 1 (HI ≤ 1.0). The Metal Pollution Index (MPI) is showing either no impact or very low contamination. An overall study on hazard identification and health risk characterization in terms of heavy metals shows contamination of some heavy metals in sharks, but there is no potential human health risk associated with consumption.


Assuntos
Metais Pesados , Tubarões , Poluentes Químicos da Água , Animais , Metais Pesados/análise , Tubarões/metabolismo , Poluentes Químicos da Água/análise , Medição de Risco , Humanos , Oligoelementos/análise , Monitoramento Ambiental , Minerais/análise
10.
Surg Endosc ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977504

RESUMO

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. METHODOLOGY: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. RESULTS: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. CONCLUSION: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings.

11.
Plant Cell Rep ; 43(7): 172, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874775

RESUMO

KEY MESSAGE: The heat stress transcription factor HSFA2e regulates both temperature and drought response via hormonal and secondary metabolism alterations. High temperature and drought are the primary yield-limiting environmental constraints for staple food crops. Heat shock transcription factors (HSF) terminally regulate the plant abiotic stress responses to maintain growth and development under extreme environmental conditions. HSF genes of subclass A2 predominantly express under heat stress (HS) and activate the transcriptional cascade of defense-related genes. In this study, a highly heat-inducible HSF, HvHSFA2e was constitutively expressed in barley (Hordeum vulgare L.) to investigate its role in abiotic stress response and plant development. Transgenic barley plants displayed enhanced heat and drought tolerance in terms of increased chlorophyll content, improved membrane stability, reduced lipid peroxidation, and less accumulation of ROS in comparison to wild-type (WT) plants. Transcriptome analysis revealed that HvHSFA2e positively regulates the expression of abiotic stress-related genes encoding HSFs, HSPs, and enzymatic antioxidants, contributing to improved stress tolerance in transgenic plants. The major genes of ABA biosynthesis pathway, flavonoid, and terpene metabolism were also upregulated in transgenics. Our findings show that HvHSFA2e-mediated upregulation of heat-responsive genes, modulation in ABA and flavonoid biosynthesis pathways enhance drought and heat stress tolerance.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico , Hordeum , Reguladores de Crescimento de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Hordeum/genética , Hordeum/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Resposta ao Choque Térmico/genética , Reguladores de Crescimento de Plantas/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Clorofila/metabolismo , Estresse Fisiológico/genética , Metabolismo Secundário/genética , Redes e Vias Metabólicas/genética , Resistência à Seca
12.
Anim Biotechnol ; 35(1): 2323592, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38770771

RESUMO

Nucleic acid aptamers have been used in the past for the development of diagnostic methods against a number of targets such as bacteria, pesticides, cancer cells etc. In the present study, six rounds of Cell-SELEX were performed on a ssDNA aptamer library against X-enriched sperm cells from Sahiwal breed cattle. Sequencing was used to examine the aptamer sequences that shown affinity for sperm carrying the X chromosome in order to find any possible X-sperm-specific sequences. Out of 35 identified sequences, 14 were selected based on bioinformatics analysis like G-Score and Mfold structures. Further validation of their specificity was done via fluorescence microscopy. The interaction of biotinylated-aptamer with sperm was also determined by visualizing the binding of streptavidin coated magnetic beads on the head region of the sperm under bright field microscopy. Finally, a real-time experiment was designed for the validation of X-sperm enrichment by synthesized aptamer sequences. Among the studied sequences, aptamer 29a exhibited a higher affinity for X sperm compared to Y sperm in a mixed population of sperm cells. By using aptamer sequence 29a, we obtained an enrichment of 70% for X chromosome bearing sperm cells.


Assuntos
Aptâmeros de Nucleotídeos , Técnica de Seleção de Aptâmeros , Espermatozoides , Cromossomo X , Masculino , Animais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Espermatozoides/química , Bovinos , Cromossomo X/genética , Técnica de Seleção de Aptâmeros/métodos
13.
J Oral Rehabil ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778703

RESUMO

BACKGROUND: In postmenopausal women (PMW), vasomotor symptoms, emotional oscillations and sleep disturbances can affect physiological and psychological functioning. However, the effect of menopause on oral health-related parameters is not been thoroughly studied. OBJECTIVE: To evaluate oral health, taste perception, eating habits, nutritional status and emotional well-being in PMW compared with a group of young and healthy pre-menopausal women (PrMW). MATERIALS AND METHODS: Two groups (Group I: PMW and Group II: PrMW) with 30 participants each, participated in the cross-sectional study. The study proforma contained measures of oral health, taste perception, nutritional status and anxiety levels of the women in both groups using validated and previously used tools were designed and implemented. The data were analysed with student t, Mann-Whitney U, and chi-squared tests to evaluate the differences between the two groups. RESULTS: The cross-sectional study indicates no major differences in oral health, taste perception, nutritional and emotional status between PMW and PrMW. Nonetheless, there was a significant difference in perception of 'front teeth lengthening in size' and change in hot and cold sensations between the groups. Furthermore, the study group with PMW tends to have fewer natural teeth than the reference group. CONCLUSION: Overall, menopause does not appear to affect oral health, taste perception, nutrition or emotional health. It is suggested that oral health and taste perception, as well as nutritional and emotional status, are associated with gradual aging processes that may or may not be affected by menopause.

14.
Eur J Neurosci ; 58(1): 2406-2425, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37203306

RESUMO

Alzheimer's disease (AD) is a neurological ailment that primarily affects the elderly and necessitates an efficient treatment regimen backed up by extensive care. Despite advancement in the in vivo imaging techniques focussing on early diagnosis of reliable biomarkers using novel magnetic resonance imaging (MRI) and positron emission topography (PET) scans, AD remains largely unexplained and effective preventative and treatment strategies are still lacking. Consequently, research groups are constantly attempting to improve its early detection, using both invasive and non-invasive techniques with established core markers like Aß and Tau (t-tau and p-tau) proteins. Unfortunately, African American and other black races are facing an increasing burden of closely associated risk factors, and only a few attempts have been made to find effective complementary and alternative therapies for AD cure and management. A greater epidemiology and natural product research are required to deal with the concurrent rise of dementia among quickly ageing African population, which so far have largely been ignored in addition to a disparity in the AD risk factors. We have tried to bring attention to the issue by reviewing up on this predisposition while generating a perspective on how race may affect AD risk and expression. This article also puts emphasis on finding new research leads from African phytodiversity while presenting several of the important species along with their biological agents found helpful in dementia related symptoms.


Assuntos
Doença de Alzheimer , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Proteínas tau , Imageamento por Ressonância Magnética , Biomarcadores , Diagnóstico Precoce , Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons
15.
Small ; 19(31): e2206680, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36932892

RESUMO

Carbon dots are defined as small carbon nanoparticles with effective surface passivation via organic functionalization. The definition is literally a description of what carbon dots are originally found for the functionalized carbon nanoparticles displaying bright and colorful fluorescence emissions, mirroring those from similarly functionalized defects in carbon nanotubes. In literature more popular than classical carbon dots are the diverse variety of dot samples from "one-pot" carbonization of organic precursors. On the two different kinds of samples from the different synthetic approaches, namely, the classical carbon dots versus those from the carbonization method, highlighted in this article are their shared properties and apparent divergences, including also explorations of the relevant sample structural and mechanistic origins for the shared properties and divergences. Echoing the growing evidence and concerns in the carbon dots research community on the major presence of organic molecular dyes/chromophores in carbonization produced dot samples, demonstrated and discussed in this article are some representative cases of dominating spectroscopic interferences due to the organic dye contamination that have led to unfound claims and erroneous conclusions. Mitigation strategies to address the contamination issues, including especially the use of more vigorous processing conditions in the carbonization synthesis, are proposed and justified.

16.
Chembiochem ; 24(18): e202300155, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37341379

RESUMO

Prodrugs are pharmacologically inactive, chemically modified derivatives of active drugs, which, following in vivo administration, are converted to the parent drugs through chemical or enzymatic cleavage. The prodrug approach holds tremendous potential to create the enhanced version of an existing pharmacological agent and leverage those improvements to augment the drug molecules' bioavailability, targeting ability, therapeutic efficacy, safety, and marketability. Especially in cancer therapy, prodrug application has received substantial attention. A prodrug can effectively broaden the therapeutic window of its parent drug by enhancing its release at targeted tumor sites while reducing its access to healthy cells. The spatiotemporally controlled release can be achieved by manipulating the chemical, physical, or biological stimuli present at the targeted tumor site. The critical strategy comprises drug-carrier linkages that respond to physiological or biochemical stimuli in the tumor milieu to yield the active drug form. This review will focus on the recent advancements in the development of various fluorophore-drug conjugates that are widely used for real-time monitoring of drug delivery. The use of different stimuli-cleavable linkers and the mechanisms of linker cleavage will be discussed. Finally, the review will conclude with a critical discussion of the prospects and challenges that might impede the future development of such prodrugs.


Assuntos
Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Neoplasias/tratamento farmacológico
17.
Electrophoresis ; 44(1-2): 44-52, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35775948

RESUMO

We have investigated the role of viscoelectric effect on diffusioosmotic flow (DOF) through a nanochannel connected with two reservoirs. The transport equations governing the flow dynamics are solved numerically using the finite element technique. We have extensively analyzed the variation of induced field due to electric double layer (EDL) phenomenon, relative viscosity as modulated by the viscoelectric effect as well as reservoir's concentration difference, and their eventual impact on the underlying flow characteristics. It is revealed that the induced electric field in the EDL enhances fluid viscosity substantially near the charged wall at a higher concentration. We have shown that neglecting viscoelectric effect in the paradigm of diffusioosmotic transport overestimates the net throughput, particularly at a higher concentration difference. Furthermore, we show that pertaining to chemiosmosis dominated regime, the average flow velocity modifies with the increase in concentration difference up to a critical value. In comparison, the rise in the strength of resistive electroosmotic actuation by the accumulation of anions in the upstream reservoir reduces the average flow velocity at a higher concentration difference. We have reported a reduction in critical concentration with the increase in viscoelectric effect. The inferences of this analysis are deemed pertinent to reveal the bearing of viscoelectric effect as a flow control mechanism pertaining to DOF at nanoscale.


Assuntos
Eletricidade , Eletro-Osmose , Eletro-Osmose/métodos
18.
Electrophoresis ; 44(21-22): 1629-1636, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36807917

RESUMO

Pertaining to the mixing of the non-Newtonian Carreau fluid under electrokinetic actuation inside a plane microchannel, we propose a new design of micromixer that involves inserting a two-part cylinder bearing zeta potential of the same sign but different magnitude in the upstream and downstream directions. We numerically solve the transport equations to predict the underlying mixing characteristics. We demonstrate that a substantial momentum difference between the microchannel's plane wall and cylinder leads to the development of a vortex in the flow pathway, which in turn, enhances mixing substantially. As shown, for a fluid having a highly shear-thinning nature, the vortex-assisted convection mixing strength increases with diffusivity of the candidate fluids. Moreover, it is shown that for the higher shear-thinning nature of the candidate fluid, an increase in cylinder radius enhances mixing efficiency and flow rate simultaneously, resulting in a "quick and efficient" mixing condition. Additionally, the fluid rheology significantly alters the kinetics of shear-induced binary aggregation. Our findings show that the shear-induced aggregation characteristic time sharply increases with increasing shear-thinning behavior of the fluid.


Assuntos
Eletro-Osmose , Reologia/métodos , Cinética , Movimento (Física)
19.
Crit Rev Biotechnol ; 43(5): 805-822, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35723574

RESUMO

The tannery is one of the leading revenue-generating sectors in developing countries. The ever-increasing demand for leather products in the global market requires converting large amounts of rawhide/skins into resilient non-putrescible finished leather. Only 20% of the raw material is converted into a finished product; the rest 80% is discarded as solid and liquid wastes during leather processing. A heavy discharge of improperly treated solid tannery waste (STW) causes a severe impact on the surrounding environment by polluting soil, surface water, and groundwater resources, posing severe hazards to human and animal health. STW comprises proteinaceous untanned and tanned waste, which requires proper treatment for eco-friendly disposal. Several strategies have been developed over the years for the reduction and recycling of STW for producing renewable energy (biogas and biohydrogen), biofuels (biodiesel and briquettes), construction material, fertilizers, commercial products (adsorbents, animal feeds, proteins, fats, and enzymes), and biodegradable packaging and non-packaging materials. In this review, we discuss various strategies adopted for recycling, reutilization, and reduction of STW in an environment-friendly manner. Furthermore, an overview of the current perspectives toward achieving a zero-waste policy is also presented to reduce the environmental burden using green-clean technology to aid the survival of present-day tanneries.


Assuntos
Resíduos Sólidos , Gerenciamento de Resíduos , Humanos , Solo , Resíduos Industriais
20.
Langmuir ; 39(47): 16797-16806, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37882459

RESUMO

For liquids used in biological applications, a smaller diffusion coefficient results in a longer mixing time. We discuss, in this endeavor, the promising potential of the AC electrothermal (ACET) effect toward modulating enhanced mixing of electrolytic liquids with higher convective strength in a novel wavy micromixer. To this end, we develop a modeling framework and numerically solve the pertinent transport equations in a three-dimensional (3D) configuration numerically. By benchmarking the developed modeling framework with the experimental results available in this paradigm, we aptly demonstrate the maximum temperature rise, flow topology, species concentration field, and mixing efficiency in the proposed configuration for a set of parameters pertinent to this analysis. We find that the maximum temperature increase in the wavy micromixer, owing to the electrothermal effect, is less than 10 K even for the higher strength of the applied voltage, implying nondegradation of biological substances within the liquid sample. We report that the formation of significant lateral flow closer to the electrodes leads to a highly three-dimensional ACET flow field, which has a significant impact on the mixing efficiency for the range of diffusive Peclet numbers considered. We also report that the wave amplitude of the mixer, when intervening with the diffusive Peclet number, strongly impacts the mixing efficiency. As witnessed in this endeavor, for the smaller diffusive Peclet number, the mixing efficiency increases with amplitude, while the effect becomes the opposite for the higher Peclet number. The results of this study seem to provide an adequate basis for the design of a novel micromixer intended for enhanced solute mixing in realistic microfluidic applications.

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