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1.
Environ Sci Technol ; 58(15): 6835-6842, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38570313

RESUMO

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.


Assuntos
Canais Iônicos , Metais , Nitritos , Elementos de Transição , Íons , Cátions Bivalentes , Membranas Artificiais , Concentração de Íons de Hidrogênio
2.
Anal Chem ; 96(15): 5922-5930, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38575388

RESUMO

Mitochondrial therapy is a promising new strategy that offers the potential to achieve precise disease diagnosis or maximum therapeutic response. However, versatile mitochondrial theranostic platforms that integrate biomarker detection and therapy have rarely been exploited. Here, we report a charge-reversal nanomedicine activated by an acidic microenvironment for mitochondrial microRNA (mitomiR) detection and ion-interference therapy. The transporter liposome (DD-DC) was constructed from a pH-responsive polymer and a positively charged phospholipid, encapsulating NaCl nanoparticles with coloading of the aggregation-induced emission (AIE) fluorogens AIEgen-DNA/G-quadruplexes precursor and brequinar (NAB@DD-DC). The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na+ in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.


Assuntos
Compostos de Bifenilo , Quadruplex G , MicroRNAs , Nanopartículas , Neoplasias , Quinaldinas , Humanos , Cloreto de Sódio , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Mitocôndrias , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente Tumoral
3.
Environ Sci Technol ; 58(15): 6487-6498, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38579165

RESUMO

The current understanding of multistress interplay assumes stresses occur in perfect synchrony, but this assumption is rarely met in the natural marine ecosystem. To understand the interplay between nonperfectly overlapped stresses in the ocean, we manipulated a multigenerational experiment (F0-F3) to explore how different temporal scenarios of ocean acidification will affect mercury toxicity in a marine copepod Pseudodiaptomus annandalei. We found that the scenario of past acidification aggravated mercury toxicity but current and persistent acidification mitigated its toxicity. We specifically performed a proteomics analysis for the copepods of F3. The results indicated that current and persistent acidification initiated the energy compensation for development and mercury efflux, whereas past acidification lacked the barrier of H+ and had dysfunction in the detoxification and efflux system, providing a mechanistic understanding of mercury toxicity under different acidification scenarios. Furthermore, we conducted a meta-analysis on marine animals, demonstrating that different acidification scenarios could alter the toxicity of several other metals, despite evidence from nonsynchronous scenarios remaining limited. Our study thus demonstrates that time and duration of ocean acidification modulate mercury toxicity in marine copepods and suggests that future studies should move beyond the oversimplified scenario of perfect synchrony in understanding multistress interaction.


Assuntos
Mercúrio , Animais , Mercúrio/toxicidade , Água do Mar , Ecossistema , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Metais
4.
J Nanobiotechnology ; 22(1): 180, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622591

RESUMO

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Fototerapia/métodos , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Oxigênio , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral
5.
J Environ Manage ; 357: 120786, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583386

RESUMO

An innovative task was undertaken to convert ubiquitous and toxic electronic waste, waste toner powder (WTP), into novel adsorbents. Alkaline modification with KOH, NaOH, and NH4OH was employed for the first time to synthesize a series of surface-modified WTP with enhanced dispersibility and adsorption capacity. XRD, XRF, FTIR, and BET analyses confirmed that the prepared KOH-WTP, NaOH-WTP, and NH4OH-WTP were oxygen-functionalized self-doped iron oxide-graphite nanocomposites. The prepared adsorbents were used to remove methylene blue and tetracycline from aqueous solutions. KOH-WTP (0.1 g/100 mL) adsorbed 80% of 10 mg/L methylene blue within 1 h, while 0.1 g/100 mL NH4OH-WTP removed 72% of 10 mg/L tetracycline in 3 h. Exploring surface chemistry by altering solution pH and temperature suggested that hydrogen bonding, electrostatic interactions, π-π electron stacking, and pore filling were plausible adsorption mechanisms. Scanning electron microscopy revealed a diminishing adsorbents porosity after adsorption proving the filling of pores by the adsorbates. KOH-WTP and NH4OH-WTP removed 77% and 61% of methylene blue and tetracycline respectively in the fourth reuse. The adsorption data of methylene blue and tetracycline fitted the Freundlich isotherm model. The maximum adsorption capacities of KOH-WTP and NH4OH-WTP for methylene blue and tetracycline were 59 mg/g and 43 mg/g respectively. The prepared adsorbents were also compared with other adsorbents to assess their performance. The transformation of waste toner powder into magnetically separable oxygen-functionalized WTP with outstanding recyclability and adsorption capacity showcases a significant advancement in sustainable wastewater treatment. This further aligns with the principles of the circular economy through the utilization of toxic e-waste in value-added applications. Additionally, magnetic separation of surface-modified WTP post-treatment can curtail filtration and centrifugation expenses and adsorbent loss during wastewater treatment.


Assuntos
Compostos Férricos , Grafite , Nanocompostos , Poluentes Químicos da Água , Azul de Metileno , Adsorção , Pós , Hidróxido de Sódio , Tetraciclina , Antibacterianos , Oxigênio , Poluentes Químicos da Água/análise , Cinética , Concentração de Íons de Hidrogênio
6.
Microbiome ; 12(1): 75, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627822

RESUMO

BACKGROUND: Microbes play vital roles across coral reefs both in the environment and inside and upon macrobes (holobionts), where they support critical functions such as nutrition and immune system modulation. These roles highlight the potential ecosystem-level importance of microbes, yet most knowledge of microbial functions on reefs is derived from a small set of holobionts such as corals and sponges. Declining seawater pH - an important global coral reef stressor - can cause ecosystem-level change on coral reefs, providing an opportunity to study the role of microbes at this scale. We use an in situ experimental approach to test the hypothesis that under such ocean acidification (OA), known shifts among macrobe trophic and functional groups may drive a general ecosystem-level response extending across macrobes and microbes, leading to reduced distinctness between the benthic holobiont community microbiome and the environmental microbiome. RESULTS: We test this hypothesis using genetic and chemical data from benthic coral reef community holobionts sampled across a pH gradient from CO2 seeps in Papua New Guinea. We find support for our hypothesis; under OA, the microbiome and metabolome of the benthic holobiont community become less compositionally distinct from the sediment microbiome and metabolome, suggesting that benthic macrobe communities are colonised by environmental microbes to a higher degree under OA conditions. We also find a simplification and homogenisation of the benthic photosynthetic community, and an increased abundance of fleshy macroalgae, consistent with previously observed reef microbialisation. CONCLUSIONS: We demonstrate a novel structural shift in coral reefs involving macrobes and microbes: that the microbiome of the benthic holobiont community becomes less distinct from the sediment microbiome under OA. Our findings suggest that microbialisation and the disruption of macrobe trophic networks are interwoven general responses to environmental stress, pointing towards a universal, undesirable, and measurable form of ecosystem changed. Video Abstract.


Assuntos
Antozoários , Microbiota , Animais , Recifes de Corais , Ecossistema , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Água do Mar , Antozoários/fisiologia
7.
Chemosphere ; 355: 141832, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38570044

RESUMO

Climate change and plastic pollution are likely the most relevant challenges for the environment in the 21st century. Developing cost-effective technologies for the bioconversion of methane (CH4) into polyhydroxyalkanoates (PHAs) could simultaneously mitigate CH4 emissions and boost the commercialization of biodegradable polymers. Despite the fact that the role of temperature, nitrogen deprivation, CH4:O2 ratio or micronutrients availability on the PHA accumulation capacity of methanotrophs has been carefully explored, there is still a need for optimization of the CH4-to-PHA bioconversion process prior to becoming a feasible platform in future biorefineries. In this study, the influence of different cultivation broth pH values (5.5, 7, 8.5 and 10) on bacterial biomass growth, CH4 bioconversion rate, PHA accumulation capacity and bacterial community structure was investigated in a stirred tank bioreactor under nitrogen deprivation conditions. Higher CH4 elimination rates were obtained at increasing pH, with a maximum value of 50.4 ± 2.7 g CH4·m-3·h-1 observed at pH 8.5. This was likely mediated by an increased ionic strength in the mineral medium, which enhanced the gas-liquid mass transfer. Interestingly, higher PHB accumulations were observed at decreasing pH, with the highest PHB contents recorded at a pH 5.5 (43.7 ± 3.4 %w·w-1). The strong selective pressure of low pH towards the growth of Type II methanotrophic bacteria could explain this finding. The genus Methylocystis increased its abundance from 34 % up to 85 and 90 % at pH 5.5 and 7, respectively. On the contrary, Methylocystis was less abundant in the community enriched at pH 8.5 (14 %). The accumulation of intracellular PHB as energy and carbon storage material allowed the maintenance of high CH4 biodegradation rates during 48 h after complete nitrogen deprivation. The results here obtained demonstrated for the first time a crucial and multifactorial role of pH on the bioconversion performance of CH4 into PHA.


Assuntos
Methylocystaceae , Poli-Hidroxialcanoatos , Poli-Hidroxibutiratos , Carbono/metabolismo , Metano/metabolismo , Methylocystaceae/metabolismo , Nitrogênio/metabolismo , Concentração de Íons de Hidrogênio
8.
PLoS One ; 19(4): e0302240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625910

RESUMO

CO2 anesthesia is the most common method for immobilizing Drosophila for research purposes. But CO2 exposure has consequences-it can impact fertility, behavior, morphogenesis, and cytoskeletal dynamics. In this respect, Drosophila is an outstanding model for studying the impact of CO2 exposure on tissues. In this study we explored the response of intracellular pH (pHi) to a one-minute CO2 pulse using a genetically encoded, ubiquitously expressed pH sensor, tpHusion, to monitor pHi within a live, intact, whole fly. We compared wild-type flies to flies lacking Imaginal disc growth factors (Idgfs), which are chitinase-like proteins that facilitate developmental processes and the innate immune response. Morphogenetic and cytoskeletal defects in Idgf-null flies are enhanced after CO2 exposure. We found that pHi drops sharply within seconds of the beginning of a CO2 pulse and recovers over several minutes. The initial profile was nearly identical in control and Idgf-null flies but diverged as the pHi returned to normal. This study demonstrates the feasibility of monitoring pH in live adult Drosophila. Studies exploring pH homeostasis are important for understanding human pathologies associated with pH dysregulation.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Humanos , Drosophila/metabolismo , Dióxido de Carbono , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Concentração de Íons de Hidrogênio , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo
9.
Braz Oral Res ; 38: e028, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38597547

RESUMO

Acidic pH can modify the properties of repair cements. In this study, volumetric change and solubility of the ready-to-use bioceramic repair cement Bio-C Repair (BCR, Angelus, Londrina, PR, Brazil) were evaluated after immersion in phosphate-buffered saline (PBS) (pH 7.0) or butyric acid (pH 4.5). Solubility was determined by the difference in initial and final mass using polyethylene tubes measuring 4 mm high and 6.70 mm in internal diameter that were filled with BCR and immersed in 7.5 mL of PBS or butyric acid for 7 days. The volumetric change was established by using bovine dentin tubes measuring 4 mm long with an internal diameter of 1.5 mm. The dentin tubes were filled with BCR at 37°C for 24 hours. Scanning was performed with micro-computed tomography (micro-CT; SkyScan 1176, Bruker, Kontich, Belgium) with a voxel size of 8.74 µm. Then, the specimens were immersed in 1.5 mL of PBS or butyric acid at and 37 °C for 7 days. After this period, a new micro-CT scan was performed. Bio-C Repair showed greater mass loss after immersion in butyric acid when compared with immersion in PBS (p<0.05). Bio-C Repair showed volumetric loss after immersion in butyric acid and increase in volume after immersion in PBS (p<0.05). The acidic pH influenced the solubility and dimensional stability of the Bio-C Repair bioceramic cement, promoting a higher percentage of solubility and decrease in volumetric values.


Assuntos
Óxidos , Materiais Restauradores do Canal Radicular , Animais , Bovinos , Solubilidade , Óxidos/química , Compostos de Cálcio/química , Microtomografia por Raio-X , Ácido Butírico , Teste de Materiais , Cimentos Dentários/química , Cimentos de Ionômeros de Vidro , Concentração de Íons de Hidrogênio , Silicatos/química , Materiais Restauradores do Canal Radicular/química
10.
Microb Biotechnol ; 17(4): e14404, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38588312

RESUMO

Acid phosphatases are enzymes that play a crucial role in the hydrolysis of various organophosphorous molecules. A putative acid phosphatase called FS6 was identified using genetic profiles and sequences from different environments. FS6 showed high sequence similarity to type C acid phosphatases and retained more than 30% of consensus residues in its protein sequence. A histidine-tagged recombinant FS6 produced in Escherichia coli exhibited extremophile properties, functioning effectively in a broad pH range between 3.5 and 8.5. The enzyme demonstrated optimal activity at temperatures between 25 and 50°C, with a melting temperature of 51.6°C. Kinetic parameters were determined using various substrates, and the reaction catalysed by FS6 with physiological substrates was at least 100-fold more efficient than with p-nitrophenyl phosphate. Furthermore, FS6 was found to be a decamer in solution, unlike the dimeric forms of crystallized proteins in its family.


Assuntos
Fosfatase Ácida , Extremófilos , Fosfatase Ácida/metabolismo , Extremófilos/genética , Extremófilos/metabolismo , Hidrólise , Sequência de Aminoácidos , Especificidade por Substrato , Concentração de Íons de Hidrogênio
11.
Water Environ Res ; 96(4): e11019, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590287

RESUMO

The Langmuir isotherm, originally developed to study the adsorption of gases, has been modified in this research to investigate the adsorption of solutes in the solution phase. The modification considers the adsorption of solvent molecules and the interactions between adsorbed particles and the species in the solution. Three equations have been obtained to calculate the contribution of these additional effects on the Gibbs free energy, enthalpy, and entropy of solute adsorption based on the new isotherm. The study evaluated the efficiency of the new isotherm in the adsorption of some metal ions in an aqueous solution and found that it is more accurate than the Langmuir isotherm and provides a deeper insight into the adsorption process in the solution phase. PRACTITIONER POINTS: Modification of the Langmuir isotherm for adsorption in solution. Comparison of the efficiency of the Langmuir and modified Langmuir isotherms. Accurate determination of ∆ H ads o $$ \Delta {H}_{ads}^o $$ and ∆ S ads o $$ \Delta {S}_{ads}^o $$ for Pb(II), Cd(II), and Ni(II) adsorption.


Assuntos
Metais , Adsorção , Cinética , Termodinâmica , Soluções , Concentração de Íons de Hidrogênio
12.
Environ Geochem Health ; 46(5): 169, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592569

RESUMO

Density functional theory (DFT) was employed to elucidate the mechanisms for ozonolysis reaction of p-nitrophenol (PNP) and its anion form aPNP. Thermodynamic data, coupled with Average Local Ionization Energies (ALIE) analysis, reveal that the ortho-positions of the OH/O- groups are the most favorable reaction sites. Moreover, rate constant calculations demonstrate that the O3 attack on the C2-C3 bond is the predominant process in the reaction between neutral PNP and O3. For the aPNP + O3 reaction, the most favorable pathways involve O3 attacking the C1-C2 and C6-C1 bonds. The rate constant for PNP ozonolysis positively correlates with pH, ranging from 5.47 × 108 to 2.86 × 109 M-1 s-1 in the natural aquatic environment. In addition, the formation of hydroxyl radicals in the ozonation process of PNP and the mechanisms of its synergistic reaction of PNP with ozone were investigated. Furthermore, the ozonation and hydroxylation processes involving the intermediate OH-derivatives were both thermodynamically and kinetic analyzed, which illustrate that OH radicals could promote the elimination of PNP. Finally, the toxic of PNP and the main products for fish, daphnia, green algae and rat were assessed. The findings reveal that certain intermediates possess greater toxicity than the original reactant. Consequently, the potential health risks these compounds pose to organisms warrant serious consideration.


Assuntos
Daphnia , Nitrofenóis , Ozônio , Animais , Ratos , Meio Ambiente , Concentração de Íons de Hidrogênio
13.
Mol Biol Rep ; 51(1): 496, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587695

RESUMO

BACKGROUND: The iono- and osmoregulatory capacities of marine teleosts, such as European sea bass (Dicentrarchus labrax) are expected to be challenged by high carbon dioxide exposure, and the adverse effects of elevated CO2 could be amplified when such fish migrate into less buffered hypo-osmotic estuarine environments. Therefore, the effects of increased CO2 on the physiological responses of European sea bass (Dicentrarchus labrax) acclimated to 32 ppt, 10 ppt and 2.5 ppt were investigated. METHODS: Following acclimation to different salinities for two weeks, fish were exposed to present-day (400 µatm) and future (1000 µatm) atmospheric CO2 for 1, 3, 7 and 21 days. Blood pH, plasma ions (Na+, K+, Cl-), branchial mRNA expression of ion transporters such as Na+/K+-ATPase (NKA), Na+/K+/2Cl- co-transporters (NKCC) and ammonia transporters (e.g. Rhesus glycoproteins Rhbg, Rhcg1 and Rhcg2) were examined to understand the iono- and osmoregulatory consequences of elevated CO2. RESULTS: A transient but significant increase in the blood pH of exposed fish acclimated at 10 ppt (day 1) and 2.5 ppt (day 21) was observed possibly due to an overshoot of the blood HCO3- accumulation while a significant reduction of blood pH was observed after 21 days at 2.5ppt. However, no change was seen at 32 ppt. Generally, Na + concentration of control fish was relatively higher at 10 ppt and lower at 2.5 ppt compared to 32 ppt control group at all sampling periods. Additionally, NKA was upregulated in gill of juvenile sea bass when acclimated to lower salinities compared to 32 ppt control group. CO2 exposure generally downregulated NKA mRNA expression at 32ppt (day 1), 10 ppt (days 3, 7 and 21) and 2.5ppt (days 1 and 7) and also a significant reduction of NKCC mRNA level of the exposed fish acclimated at 32 ppt (1-3 days) and 10 ppt (7-21 days) was observed. Furthermore, Rhesus glycoproteins were generally upregulated in the fish acclimated at lower salinities indicating a higher dependance on gill ammonia excretion. Increased CO2 led to a reduced expression of Rhbg and may therefore reduce ammonia excretion rate. CONCLUSION: Juvenile sea bass were relatively successful in keeping acid base balance under an ocean acidification scenario. However, this came at a cost for ionoregulation with reduced NKA, NKCC and Rhbg expression rates as a consequence.


Assuntos
Bass , Animais , Bass/genética , Dióxido de Carbono , Amônia , Concentração de Íons de Hidrogênio , Água do Mar , Macaca mulatta , Glicoproteínas , RNA Mensageiro
14.
Nat Commun ; 15(1): 2917, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575562

RESUMO

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment. In summary, SNS-101, currently in Phase I clinical trials, emerges as a promising therapeutic biologic for a wide range of patients whose cancer is refractory to current immunotherapy regimens.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Camundongos , Animais , Antígenos B7 , Anticorpos , Neoplasias/tratamento farmacológico , Imunoterapia , Concentração de Íons de Hidrogênio , Microambiente Tumoral
15.
Anal Chim Acta ; 1302: 342506, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38580410

RESUMO

BACKGROUND: Mitophagy plays indispensable roles in maintaining intracellular homeostasis in most eukaryotic cells by selectively eliminating superfluous components or damaged organelles. Thus, the co-operation of mitochondrial probes and lysosomal probes was presented to directly monitor mitophagy in dual colors. Nowadays, most of the lysosomal probes are composed of groups sensitive to pH, such as morpholine, amine and other weak bases. However, the pH in lysosomes would fluctuate in the process of mitophagy, leading to the optical interference. Thus, it is crucial to develop a pH-insensitive probe to overcome this tough problem to achieve exquisite visualization of mitophagy. RESULTS: In this study, we rationally prepared a pH-independent lysosome probe to reduce the optical interference in mitophagy, and thus the process of mitophagy could be directly monitored in dual color through cooperation between IVDI and MTR, depending on Förster resonance energy transfer mechanism. IVDI shows remarkable fluorescence enhancement toward the increase of viscosity, and the fluorescence barely changes when pH varies. Due to the sensitivity to viscosity, the probe can visualize micro-viscosity alterations in lysosomes without washing procedures, and it showed better imaging properties than LTR. Thanks to the inertia of IVDI to pH, IVDI can exquisitely monitor mitophagy with MTR by FRET mechanism despite the changes of lysosomal pH in mitophagy, and the reduced fluorescence intensity ratio of green and red channels can indicate the occurrence of mitophagy. Based on the properties mentioned above, the real-time increase of micro-viscosity in lysosomes during mitophagy was exquisitely monitored through employing IVDI. SIGNIFICANCE AND NOVELTY: Compared with the lysosomal fluorescent probes sensitive to pH, the pH-inert probe could reduce the influence of pH variation during mitophagy to achieve exquisite visualization of mitophagy in real-time. Besides, the probe could monitor the increase of lysosomal micro-viscosity in mitophagy. So, the probe possesses tremendous potential in the visualization of dynamic changes related to lysosomes in various physiological processes.


Assuntos
Corantes Fluorescentes , Mitofagia , Humanos , Concentração de Íons de Hidrogênio , Viscosidade , Células HeLa , Corantes Fluorescentes/química , Lisossomos/química
16.
Pflugers Arch ; 476(4): 457-465, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581526

RESUMO

Soluble adenylyl cyclase (sAC) differs from transmembrane adenylyl cyclases (tmAC) in many aspects. In particular, the activity of sAC is not regulated by G-proteins but by the prevailing bicarbonate concentrations inside cells. Therefore, sAC serves as an exquisite intracellular pH sensor, with the capacity to translate pH changes into the regulation of localization and/or activity of cellular proteins involved in pH homeostasis. In this review, we provide an overview of literature describing the regulation of sAC activity by bicarbonate, pinpointing the importance of compartmentalization of intracellular cAMP signaling cascades. In addition, examples of processes involving proton and bicarbonate transport in different cell types, in which sAC plays an important regulatory role, were described in detail.


Assuntos
Adenilil Ciclases , AMP Cíclico , Adenilil Ciclases/metabolismo , AMP Cíclico/metabolismo , Bicarbonatos/metabolismo , Transdução de Sinais/fisiologia , Concentração de Íons de Hidrogênio
17.
Inorg Chem ; 63(15): 6776-6786, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38572830

RESUMO

The heme-containing chlorite dismutases catalyze the rapid and efficient decomposition of chlorite (ClO2-) to yield Cl- and O2, and the catalytic efficiency of chlorite dismutase from Dechloromonas aromatica (DaCld) in catalyzing the decomposition of bromite (BrO2-) was dependent on pH, which was supposed to be caused by the conversion of active Cpd I to the inactive Cpd II by proton-coupled electron transfer (PCET) from the pocket Tyr118 to the propionate side chain of heme at high pH. However, the direct evidence of PCET and how the pH affects the efficiency of DaCld, as well as whether Cpd II is really inactive, are still poorly understood. Here, on the basis of the high-resolution crystal structures, the computational models in both acidic (pH 5.0) and alkaline (pH 9.0) environments were constructed, and a series of quantum mechanical/molecular mechanical calculations were performed. On the basis of our calculation results, the O-Br bond cleavage of BrO2- always follows the homolytic mode to generate Cpd II rather than Cpd I. It is different from the O-O cleavage of O2/H2O2 or peracetic acid catalyzed by the other heme-containing enzymes. Thus, in the subsequent O-O rebound reaction, it is the Fe(IV)═O in Cpd II that combines with the O-Br radical. Because the porphyrin ring in Cpd II does not bear an unpaired electron, the previously suggested PCET from Tyr118 to the propionate side chain of heme was not theoretically recognized in an alkaline environment. In addition, the O-O rebound step in an alkaline solution corresponds to an energy barrier that is larger than that in an acidic environment, which can well explain the pH dependence of the activity of DaCld. In addition, the protonation state of the propionic acid side chains of heme and the surrounding hydrogen bond networks were calculated to have a significant impact on the barriers of the O-O rebound step, which is mainly achieved by affecting the reactivity of the Fe(IV)═O group in Cpd II. In an acidic environment, the relatively weaker coordination of the O2 atom to Fe leads to its higher reactivity toward the O-O rebound reaction. These observations may provide useful information for understanding the catalysis of chlorite dismutases.


Assuntos
Betaproteobacteria , Cloretos , Peróxido de Hidrogênio , Oxirredutases , Propionatos , Peróxido de Hidrogênio/química , Catálise , Prótons , Concentração de Íons de Hidrogênio , Heme/química
18.
Neuroimaging Clin N Am ; 34(2): 271-280, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604711

RESUMO

Acute stroke imaging plays a vital and time-sensitive role in therapeutic decision-making. Current clinical workflows widely use computed tomography (CT) and magnetic resonance (MR) techniques including CT and MR perfusion to estimate the volume of ischemic penumbra at risk for infarction without acute intervention. The use of imaging techniques aimed toward evaluating the metabolic derangements underlying a developing infarct may provide additional information for differentiating the penumbra from benign oligemia and infarct core. The authors review several modalities of metabolic imaging including PET, hydrogen and oxygen spectroscopy, sodium MRI, and pH-weighted MRI.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/patologia , Oxigênio , Acidente Vascular Cerebral/terapia , Imageamento por Ressonância Magnética , Análise Espectral , Tomografia por Emissão de Pósitrons/métodos , Infarto , Concentração de Íons de Hidrogênio
19.
AAPS PharmSciTech ; 25(4): 83, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605211

RESUMO

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16 mg/ml) and sonication time (5, 10, 15 min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5 mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6 months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.


Assuntos
Hemangiossarcoma , Polietilenoglicóis , Polietilenoimina , Polímeros , Animais , Cães , Nanogéis , Sorafenibe , Concentração de Íons de Hidrogênio , Portadores de Fármacos , Microambiente Tumoral
20.
Luminescence ; 39(4): e4741, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38605268

RESUMO

In the present study, a first validated and green spectrofluorimetric approach for its assessment and evaluation in different matrices was investigated. After using an excitation wavelength of 345 nm, Roxadustat (ROX) demonstrates a highly native fluorescence at an emission of 410 nm. The influences of experimental factors such as pH, diluting solvents, and different organized media were tested, and the most appropriate solvent choice was ethanol. It was confirmed that there was a linear relationship between the concentration of ROX and the relative fluorescence intensity in the range 60.0-1000.0 ng ml-1, with the limit of detection and limit of quantitation, respectively, being 17.0 and 53.0 ng ml-1. The mean recoveries % [±standard deviation (SD), n = 5] for pharmaceutical preparations were 100.11% ± 2.24%, whereas for plasma samples, they were 100.08 ± 1.08% (±SD, n = 5). The results obtained after the application of four greenness criteria, Analytical Eco-Scale metric, NEMI, GAPI, and AGREE metric, confirmed its eco-friendliness. In addition, the whiteness meter (RGB12) confirmed its level of sustainability. The International Council for Harmonisation (ICH) criteria were used to verify the developed method through the study in both spiked plasma samples and content uniformity evaluation. An appropriate standard for various applications in industry and quality control laboratories was developed.


Assuntos
Hematínicos , Humanos , Limite de Detecção , Espectrometria de Fluorescência/métodos , Eritropoese , Concentração de Íons de Hidrogênio , Solventes/química , Comprimidos/química , Isoquinolinas
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