Uptake Process Research Articles

MiR-122-5p is involved in posttranscriptional regulation of the mitochondrial thiamin pyrophosphate transporter (SLC25A19) in pancreatic acinar cells.

Thiamin (vitamin B1) plays a vital role in cellular energy metabolism/ATP production. Pancreatic acinar cells (PACs) obtain thiamin from circulation and convert it to thiamin pyrophosphate (TPP) in the cytoplasm. TPP is then taken up by the mitochondria via a carrier-mediated process that involves the mitochondrial TPP transporter (MTPPT; encoded by the gene SLC25A19). We have previously characterized different aspects of the mitochondrial carrier-mediated TPP uptake process, but nothing is known about its possible regulation at the posttranscriptional level. We address this issue in the current investigations focusing on the role of miRNAs in this regulation. First, we subjected the human (and rat) 3'-untranslated region (3'-UTR) of the SLC25A19 to three in-silico programs, and all have identified putative binding sites for miR-122-5p. Transfecting pmirGLO-hSLC25A19 3'-UTR into rat PAC AR42J resulted in a significant reduction in luciferase activity compared with cells transfected with pmirGLO-empty vector. Mutating as well as truncating the putative miR-122-5p binding sites in the hSLC25A19 3'-UTR led to abrogation of inhibition in luciferase activity in PAC AR42J. Furthermore, transfecting/transducing PAC AR42J and human primary PACs with mimic of miR-122-5p led to a significant inhibition in the level of expression of the MTPPT mRNA and protein as well as in mitochondrial carrier-mediated TPP uptake. Conversely, transfecting PAC AR42J with an inhibitor of miR-122-5p increased MTPPT expression and function. These findings show, for the first time, that expression and function of the MTPPT in PACs are subject to posttranscriptional regulation by miR-122-5p.NEW & NOTEWORTHY This study shows that the expression and function of mitochondrial TPP transporter (MTPPT) are subject to posttranscriptional regulation by miRNA-122-5p in pancreatic acinar cells.

A new model for simulating root water uptake by vegetation under the impact of a dynamic groundwater table in arid regions

AbstractEcological water conveyance is an effective measure to mitigate or reverse vegetation ecosystem degradation in arid regions, which can lead to frequent fluctuations in the groundwater table. The depth of soil water that vegetation takes up varies in response to groundwater table fluctuations in arid environments. To better characterize the root water uptake process under dynamic changes in the groundwater table in arid regions, this study proposed a new model for simulating root water uptake. The model reduces the dominant effect of root density on water uptake by introducing a correction factor and accounts for the effect of changes in the water content profile on root water uptake in arid areas. The new model was incorporated into the HYDRUS code and tested against the monitoring data of typical vegetation in the arid region of northwestern China. The results demonstrated that the soil water content simulated by the new model matched well with the observed data, which was consistent with the water uptake process under the fluctuations of the groundwater table at the study site. Compared with other models, this model can flexibly alter water uptake layers according to soil moisture conditions in arid conditions, thus providing a new method to depict the dynamic process of water uptake influenced by fluctuations in the groundwater table.

Influence of oxygen uptake through the liver surface on the metabolism of ex vivo perfused liver during hypoxia

The low quality of transplants having undergone hypoxic injury can lead to postoperative complications. The aim of the present research is to estimate, by means of mathematical modeling, how the process of oxygen uptake through the liver surface influences the metabolism of ex vivo perfused liver under hypoxia. The value of oxygen uptake through the surface was established to depend on the degree of oxygenation of the perfusion medium. A decrease in the oxygenation of the perfusion medium resulted in a decreased oxygen uptake through the liver surface. Stoichiometric modeling of the liver metabolism shows that upon the decreased oxygenation of the perfusion medium more energy is required for the process of oxygen uptake through the surface even at a lower level as compared to the normal oxygen supply. The application of the Pareto optimality allows estimating the optimum distribution of the energy resources in liver under ex vivo conditions. Both upon the normal and decreased oxygenation of the perfusion medium, the phenomenon of “free competition” for the resource was observed, with the energy being optimally distributed among all the metabolic fluxes. Moreover, this energy is also spent on the accompanying processes, e.g. for the transport of interstitial fluid.

A refined toxicokinetic model for quantifying the interaction between Cd and Cu in zebrafish larvae

The interaction between metals is ubiquitous, but there is still a lack of quantitative models considering the interaction between metals, which leads to the deviations in predicting the joint toxicity of metals. The present study estimated the uptake rate constants (kin) and elimination rate constants (kout) and elucidated how the presence of one metal (Cu or Cd) affects the absorption and excretion of another metal (Cd or Cu) in zebrafish larvae. The results showed that Cd and Cu inhibited each other in the process of absorption and excretion by comparing separately kin and kout of Cd or Cu with the other metal Cu or Cd mixed concentrations increased, thereby affecting the Cd and Cu bioaccumulation in the zebrafish larvae. Then the interactions between Cd and Cu in the uptake and elimination processes were quantified to obtain a refined toxicokinetic model. Verification with independent experiment data showed that the refined toxicokinetic model could significantly improve the prediction of the Cd or Cu bioaccumulation in the zebrafish larvae. This study contributes to understand the toxicokinetic process of the Cd-Cu mixture in the zebrafish larvae, and the developed model could be used to predict the toxicity of the metal mixtures.

Uptake of Hydrogen Peroxide from the Gas Phase to Grain Boundaries: A Source in Snow and Ice.

Hydrogen peroxide is a primary atmospheric oxidant significant in terminating gas-phase chemistry and sulfate formation in the condensed phase. Laboratory experiments have shown an unexpected oxidation acceleration by hydrogen peroxide in grain boundaries. While grain boundaries are frequent in natural snow and ice and are known to host impurities, it remains unclear how and to which extent hydrogen peroxide enters this reservoir. We present the first experimental evidence for the diffusive uptake of hydrogen peroxide into grain boundaries directly from the gas phase. We have machined a novel flow reactor system featuring a drilled ice flow tube that allows us to discern the effect of the ice grain boundary content on the uptake. Further, adsorption to the ice surface for temperatures from 235 to 258 K was quantified. Disentangling the contribution of these two uptake processes shows that the transfer of hydrogen peroxide from the atmosphere to snow at temperatures relevant to polar environments is considerably more pronounced than previously thought. Further, diffusive uptake to grain boundaries appears to be a novel mechanism for non-acidic trace gases to fill the highly reactive impurity reservoirs in snow's grain boundaries.

An eco-friendly chitosan-diethylaminoethyl cellulose composite: In-depth analysis of lead (II) and arsenic(V) decontamination from water with molecular perspectives

Water pollution from heavy metal ions, such as lead (II) and arsenic (V), is a widespread problem that has spurred researchers to look for efficient, environmentally acceptable treatment methods. In this context, the present study explores the potentiality of a novel, low-cost biosorbent material for the efficient removal of these toxic contaminants. A chitosan crosslinked@diethylaminoethyl cellulose (Cs@DEAE-C) composite was synthesized by crosslinking chitosan and diethylaminoethyl cellulose (DEAE-C) and employed to adsorb Pb(II) and As(V) from water. The monolayer adsorption capacity was found to be 218.71 mg/g for Pb(II) and 41.98 mg/g for As(V), respectively while the uptake process involved chemisorption. The adsorption capability of Cs@DEAE-C for As(V) and Pb(II) was decreased when phosphate and nitrate ions were present. Desorption studies demonstrated that Cs@DEAE-C effectively removed As(V) and Pb(II) for up to five adsorption–desorption cycles. Uncross-linked carbonyl (C = O) and hydroxyl (–OH) groups were found to be the main adsorptive sites for Pb(II) uptake, whereas uncross-linked hydroxyl (–OH) and –NH2 groups were found to be crucial for As(V) absorption. The self-diffusion coefficient values from molecular dynamics (MD) simulation revealed that electrostatic interactions hinder the mobility of metal ions limiting their diffusion ability. This study highlights the efficiency of the low-cost chitosan composite for contaminant removal and suggests its potential applicability in treating real wastewater for other pollutants. Further research could focus on optimizing the synthesis process and exploring the composite's efficacy for additional contaminants.

Computational Insights on the Chemical Reactivity of Functionalized and Crosslinked Polyketones to Cu2+ Ion for Wastewater Treatment.

Today, the high concentrations of copper found in water resources result in an urgent problem to solve since human health and aquatic ecosystems have been affected. Functionalized crosslinked polyketone resins (XLPK) have demonstrated high performance for the uptake of heavy metals in water solutions. In addition, its green chemical synthesis makes these resins very attractive as sorbents for metal ions contained in wastewater. XLPK are not soluble in aqueous media and do not require any catalyst, solvent, or harsh conditions to carry out the uptake process. In this paper, a series of functionalized XLPK with pending amino-derivatives namely; butylamine (BA), amino 2-propanol (A2P), 4-(aminomethyl) benzoic acid (HAMC), 6-aminohexanoic acid (PAMBA), and 1,2 diamino propane (DAP) directly attached to the pyrrole backbone of the polymers and crosslinked by di-amine derivatives was investigated using Density Functional Theory (DFT) calculations. Our computational analysis revealed that dipole-dipole interactions played a crucial role in enhancing the adsorption of Cu2+ ions onto XLPKs. The negatively charged ketone moieties and functional groups within XLPKs were identified as key adsorption sites for the selective binding of Cu2+ ions. Additionally, we found that XLPKs exhibited strong electrostatic interactions primarily through the -NH2 and -C=O groups. Evaluation of the adsorption energies in XLPK-Cu(II) complexes showed that the DAP-Cu(II) complex exhibited the highest stability, attributed to strong Cu(II)-N binding facilitated by the amino moiety (-NH2). The remaining XLPKs displayed binding modes involving oxygen atoms (Cu(II)-O) within the ketone moieties in the polymer backbone. Furthermore, the complexation and thermochemical analysis emphasized the role of the coordinator atom (N or O) and the coordinating environment, in which higher entropic effects involved in the adsorption of Cu2+ ions onto XLPKs describes a lower spontaneity of the adsorption process. The adsorption reactions were favored at lower temperatures and higher pressures. These findings provide valuable insights into the reactivity and adsorption mechanisms of functionalized and crosslinked polyketones for Cu2+ uptake, facilitating the design of high-performance polymeric resins for water treatment applications.

Removal of Copper Ions onto Walnut Shells by Using Batch and Continuous Fluidized Bed

An agricultural waste (walnut shell) was undertaken to remove Cu(II) from aqueous solutions in batch and continuous fluidized bed processes. Walnut shell was found to be effective in batch reaching 75.55% at 20 and 200 rpm, when pH of the solution adjusted to 7. The equilibrium was achieved after 6 h of contacting time. The maximum uptake was 11.94mg/g. The isotherm models indicated that the highest determination coefficient belongs to Langmuir model. Cu (II) uptake process in kinetic rate model followed the pseudo-second-order with determination coefficient of 0.9972. More than 95% of the Cu(II) were adsorbed on the walnut shells within 6 h at optimum agitation speed of 800 rpm. The main functional groups responsible for biosorption of Cu(II) onto walnut shell were hydroxyl, carbonyl,carboxylate, carboxylic acids, alcohols groups, and aromatic compounds. In continuous system, fluidized bed column at 20 , and pH 7 was carried out to study the effects of various parameters like (flow rate,bed depth, and initial concentration). The time of breakthrough was 97 min when the initial concentration (Co= 20mg/l), bed depth (L=10cm), and flowrate (Q=10l/h)

Neolamarckia cadamba (cadamba) waste pulp as a natural and techno-economic scavenger for methylene blue from aqueous solutions

In this work, Neolamarckia cadamba (cadamba), also known as bur flower tree has been exercised to demonstrate as an excellent methylene blue scavenger from simulated as well as industrial wastewater. The particle morphology and structural insights were gained from FESEM, BET surface area, FTIR, and pHZPC. The adsorption behavior was mapped by different physico-chemical parameters such as contact time, pH, input concentration, and temperature. Experimental data reveal rapid adsorption, and >90% uptake was successful within the first 15 min and reaches equilibrium by 45 min (removal efficiency = 94.15%) at neutral pH. The maximum adsorption capacity was found to be 115.60 mg/g. The uptake process follows pseudo-second-order kinetics (R2 = 0.99), confirming a chemisorption process while the Langmuir model (R2 = 0.99) satisfactorily addresses the adsorption path. Thermodynamic parameters suggest a spontaneous, feasible, and exothermic process with increased entropy. Spent adsorbent could easily be regenerated in up to 74% using 1:1 MeOH/H2O with a potential of three-cycle use. Real-time efficacy has been established with an MB containing industrial effluent and up to 44.70% adsorption, which confirms the material’s practical applicability. Statistical reliability was confirmed by the relative standard deviation. Altogether, the present material offers clean and green removal of methylene blue dye from versatile wastewater.

Mechanisms of Nutrient Uptake and Assimilation Processes in Some Plants: A Review

Nutrient demands of plants are fulfilled via nutrient uptake by the roots, even though minor quantities of certain nutrients might be assimilated via leaves. For the reason that the majority of nutrients are assimilated by roots, an understanding of root morphology and cell structure is crucial in knowing this basic plant process. Nutrient achievement by plants hinges on ion applications on superficial, root assimilation capacity, and plant requirement. Movement of ion in plant cells is classified into active and passive. Ion concentrations in the cytoplasm of plant cells are frequently and considerably observed to be greater than in soil solutions. Consequently, roots ought to be able to take up ions in contrast to broadly diverse concentration gradients. Currently, two major theories of ion transport across membranes are reported in literature: carrier theory where carrier agents accountable for transferring ions from one side of membrane to the other; encounter specific ions for which they have attraction, form carrier ion complexes; and move across membranes and connecting ATPase theory of ion transport; which is related with the plasmalemma and is activated by cations; the ion pump theory, which is a demanding proces, transporting via electrochemical gradient. Measurements of ion uptake could be achieved through tracer techniques. Long-distance transport of ions to shoots happens in the vascular system, with water being the transporting agent. New and stimulating developments in mineral uptake mechanism of plants have momentously added to our understanding of the function of nutrients uptake in plants. Most research comparative to physiology of nutrient uptake has been conducted under controlled environment by means of particular nutrient cultures in the growth medium.

Development of metakaolin-based geopolymer for selenium oxyanions uptake through in-situ ettringite formation

Studies have demonstrated the remarkable capacity of metakaolin-based geopolymers for the uptake of cationic radionuclides, such as Cs+ and Sr2+. However, the lack of uptake ability towards anionic radionuclides represents a potential avenue for improvement in utilising this material for nuclear waste disposal applications. Additionally, the prevalence of ettringite as an anion exchange agent formed in alkaline environments, such as cement hydration, is widely acknowledged in the field. However, no previous studies have been conducted to explore the utilisation of the advantageous qualities of both metakaolin-based geopolymer and ettringite in developing a comprehensive incorporation process for both cationic and anionic radionuclides. In this study, compositions and sets of preparation conditions were proposed to modify metakaolin-based geopolymer, resulting in the in-situ formation of ettringite, with the aim of enhancing its uptake capabilities for selenium oxyanions. The uptake behaviour and mechanism of ettringite, and geopolymer with in-situ ettringite, were proposed through co-precipitation experiments, binding and structural analysis. The results reveal that the ettringite can uptake SeO32- and SeO42- through co-precipitation; however, its effectiveness is limited to SeO32- in the uptake process, where the mechanism is contingent on the concentration of Se oxyanions present. On the other hand, modified geopolymer with in-situ ettringite retained its capacity to uptake cationic radionuclides such as Cs+ and Sr2+ while evolving to exhibit an ability to uptake SeO32-. Thermodynamic modelling was carried out according to the ion exchange mechanism, which effectively predicts the uptake of SeO32- at low concentrations. The proposed composition and preparation conditions hold the potential for developing an effective incorporation process for cationic and anionic radionuclides. The outcomes of this research enhance the understanding of the uptake behaviour of Se oxyanions by ettringite and provide insight into the potential of metakaolin-based geopolymers to immobilise anions.

Conjunctive and concentration dependent effects of nanoscale zinc and boron on the physiological, biochemical, nutrient uptake, and translocation processes in peanut (Arachis hypogaea L.)

In the present investigation, different concentrations (150, 200, 300, 400, and 500 mg/L) of nanoscale zinc oxide (ZnO) and boron (B) were applied through foliar spray (pot culture) to evaluate their effects on the growth and biochemical parameters of peanut. Nanoscale zinc oxide and nano boron were prepared using modified oxalate decomposition and encapsulation methods, respectively, and were characterized using techniques such as, X-ray diffraction (XRD), dynamic light scattering (DLS), ultraviolet–visible (UV–vis) spectroscopy, and transmission electron microscopy (TEM). The average size (37.2 nm, 53.6 nm) and zeta potential (−37.7 mV, −28.3 mV) of nano ZnO and nano boron were measured, respectively. Fourier transform infrared spectroscopic (FT-IR) studies revealed the functional groups that are present in the hydrosols. Highest germination percentage (98.7% and 96%), seedling vigor index (2359 and 1325) and total chlorophyll content (3.28 and 2.24 mg g−1) were recorded at 500 mg/L of nano zinc oxide and nano boron. Significantly higher peroxidase, catalase, superoxide dismutase (SOD) enzymatic activities, pod yield (39.76 g pot−1 and 38.14 g pot−1) and haulm yield (49.56 g pot−1 and 47.05 g pot−1) were also recorded with the application of nano ZnO and boron @ 500 mg/L. Translocation of nanoscale nutrients through stomata was clearly observed. Significant nutrient uptake with the foliar application of nanoscale nutrients has been recorded. The performance of groundnut (in terms of yield, quality and nutrient uptake) was significantly enhanced with the application of nanoscale nutrients and this point to achieving the nutrient bio-fortification with the desired levels for the betterment of human health.

Copper metabolism and hepatocellular carcinoma: current insights.

Copper is an essential trace element that acts as a cofactor in various enzyme active sites in the human body. It participates in numerous life activities, including lipid metabolism, energy metabolism, and neurotransmitter synthesis. The proposal of "Cuproptosis" has made copper metabolism-related pathways a research hotspot in the field of tumor therapy, which has attracted great attention. This review discusses the biological processes of copper uptake, transport, and storage in human cells. It highlights the mechanisms by which copper metabolism affects hepatocellular carcinogenesis and metastasis, including autophagy, apoptosis, vascular invasion, cuproptosis, and ferroptosis. Additionally, it summarizes the current clinical applications of copper metabolism-related drugs in antitumor therapy.

A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept.

Understanding the extended clearance concept and establishing a physiologically based pharmacokinetic (PBPK) model are crucial for investigating the impact of changes in transporter and metabolizing enzyme abundance/functions on drug pharmacokinetics in blood and tissues. This mini-review provides an overview of the extended clearance concept and a PBPK model that includes transporter-mediated uptake processes in the liver. In general, complete in vitro and in vivo extrapolation (IVIVE) poses challenges due to missing factors that bridge the gap between in vitro and in vivo systems. By considering key in vitro parameters, we can capture in vivo pharmacokinetics, a strategy known as the top-down or middle-out approach. We present the latest progress, theory, and practice of the Cluster Gauss-Newton method, which is used for middle-out analyses. As examples of poor IVIVE, we discuss "albumin-mediated hepatic uptake" and "time-dependent inhibition" of OATP1Bs. The hepatic uptake of highly plasma-bound drugs is more efficient than what can be accounted for by their unbound concentration alone. This phenomenon is referred to as "albumin-mediated" hepatic uptake. IVIVE was improved by measuring hepatic uptake clearance in vitro in the presence of physiologic albumin concentrations. Lastly, we demonstrate the application of Cluster Gauss-Newton method-based analysis to the target-mediated drug disposition of bosentan. Incorporating saturable target binding and OATP1B-mediated hepatic uptake into the PBPK model enables the consideration of nonlinear kinetics across a wide dose range and the prediction of receptor occupancy over time. SIGNIFICANCE STATEMENT: There have been multiple instances where researchers' endeavors to unravel the underlying mechanism of poor in vitro-in vivo extrapolation have led to the discovery of previously undisclosed truths. These include 1) albumin-mediated hepatic uptake, 2) the target-mediated drug disposition in small molecules, and 3) the existence of a trans-inhibition mechanism by inhibitors for OATP1B-mediated hepatic uptake of drugs. Consequently, poor in vitro-in vivo extrapolation and the subsequent inquisitiveness of scientists may serve as a pivotal gateway to uncover hidden mechanisms.

Unraveling Complexities in the Absorption and Disposition Kinetics of Abiraterone via Iterative PBPK Model Development and Refinement.

Abiraterone is a first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1), and its pharmacokinetic (PK) profile is susceptible to intrinsic and extrinsic variabilities. Potential associations between abiraterone concentrations and pharmacodynamic consequences in prostate cancer may demand further dosage optimization to balance therapeutic outcomes. Consequently, we aim to develop a physiologically based pharmacokinetic (PBPK) model for abiraterone via a middle-out approach to prospectively interrogate the untested, albeit clinically relevant, scenarios. To characterize in vivo hydrolysis of prodrug abiraterone acetate (AA) and supersaturation of abiraterone, in vitro aqueous solubility data, biorelevant measurements, and supersaturation and precipitation parameters were utilized for mechanistic absorption simulation. CYP3A4-mediated N-oxidation and sulfotransferase 2A1-catalyzed sulfation of abiraterone were subsequently quantified in human liver subcellular systems. Iterative PBPK model refinement involved evaluation of potential organic anion transporting polypeptide (OATP)-mediated abiraterone uptake in transfected cells in the absence and presence of albumin. The developed PBPK model recapitulated the duodenal concentration-time profile of both AA and abiraterone after simulated AA administration. Our findings established abiraterone as a substrate of hepatic OATP1B3 to recapitulate its unbound metabolic intrinsic clearance. Further consideration of a transporter-induced protein-binding shift established accurate translational scaling factors and extrapolated the sinusoidal uptake process. Subsequent simulations effectively predicted the PK of abiraterone upon single and multiple dosing. Our systematic development of the abiraterone PBPK model has demonstrated its application for the prospective interrogation of the individual or combined influences of potential interindividual variabilities influencing the systemic exposure of abiraterone.

Transferrin receptor-targeting property of pabinafusp alfa facilitates its uptake by various types of human brain-derived cells in vitro

Pabinafusp alfa, which is an anti-mucopolysaccharidosis II drug, consists of iduronate-2-sulfatase (IDS) genetically fused with an anti-transferrin receptor (TfR) antibody. While IDS is known to enter cells via mannose-6-phosphate receptor (M6PR)-mediated endocytosis, the anti-TfR antibody moiety of pabinafusp alfa is supposed to trigger the TfR-mediated transcytosis involved in its blood-brain barrier (BBB) penetration to deliver IDS into the brain, which thus makes it effective for treatment of brain symptoms of the disease. However, since these uptake processes remain unexamined in vitro, this study aims at elucidating how human brain cells manipulate these receptors to facilitate pabinafusp alfa uptake. The results of pabinafusp alfa uptake assays showed that the TfR played an primary role in its uptake by brain microvascular endothelial cells. The TfR contribution was also found in neuronal cells at levels comparable to M6PR. Interestingly, the predominant roles of TfR over M6PR in pabinafusp alfa uptake were also observed in astrocytes and pericytes. To summarize, our results support the TfR-targeting strategy of pabinafusp alfa for facilitating its BBB penetration while simultaneously identifying previously unnoticed TfR roles in its uptake into human neuronal and non-neuronal brain cells. These findings are certain to provide important insights into the mechanisms behind clinical actions of pabinafusp alfa.

Endocytic pathways of pathogenic protein aggregates in neurodegenerative diseases.

Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aβ, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species.

Alleviation of chromium stress in plants using metal and metal oxide nanoparticles.

Chromium (Cr), one of the hazardous pollutants, exists predominantly as Cr(VI) and Cr(III) in the environment. Cr(VI) is more toxic than Cr(III) due to its high mobility and solubility. Elevated levels of Cr in agricultural soil due to various anthropogenic activities cause Cr accumulation in plants, resulting in a significant reduction in plant yield and quality due to Cr-induced physiological, biochemical and molecular alterations. It can infiltrate the food chain through crop plants and cause harmful effects in humans via biomagnification. Cr(VI) is linked to cancer in humans. Therefore, mitigation strategies are required to remediate Cr-polluted soils and limit its accumulation in plants for safe food production. Recent research on metal and metal oxide nanoparticles (NPs) has shown that they can effectively reduce Cr accumulation and phytotoxicity. The effects of these NPs are influenced by their type and dose, exposure method, plant species and experimental settings. In this review, we present an up-to-date compilation and comprehensive analysis of the existing literature regarding the process of uptake and distribution of Cr and impact and potential mechanisms of metal and metal oxide nanoparticles led mitigation of Cr-induced stress in plants. We have also discussed recent developments, existing research gaps and future research directions in the field of Cr stress mitigation by NPs in plants. Overall, this review can provide valuable insights in reducing Cr accumulation and toxicity using metal and metal oxide nanoparticles, thereby promoting safe and sustainable cultivation of food and phytostabilization of Cr-polluted soil.

PTEN: The Potential Therapeutic Target of Diabetes Mellitus

Diabetes mellitus is a metabolic disease characterized by high blood glucose levels. The cause of glucose control failure is decreased insulin production by pancreatic β-cells and insulin resistance. Both lead to the obstacle of glucose uptake into cells. The mechanism of glucose uptake into cells is crucial in carbohydrate metabolism. This mechanism aims to produce energy in the form of ATP. The main signaling pathway after the process of glucose uptake is the PI3K/Akt pathway. This pathway involves many proteins activated by phosphorylation mechanisms. One of the proteins involved in this pathway is PTEN, a PI3K regulator. PTEN activity can dephosphorylate PI3K so that the insulin signaling pathway becomes blocked and glucose cannot be uptaken into cells. It causes blood glucose levels to increase. The role of PTEN in inhibiting the PI3K/Akt pathway seems to be a crucial matter to observe. By inhibiting PTEN activity, the insulin signaling pathway is expected to work properly. We have searched, read, analyzed, and summarized various studies regarding the potential of PTEN to reduce diabetes mellitus cases. In some research articles, the use of active compounds and therapy using stem cells to inhibit PTEN activity has shown good progress in the insulin signaling pathway. Based on these, it can be an option to make PTEN a target for diabetes mellitus therapy.

Environmentally relevant doses of endocrine disrupting chemicals affect male fertility by interfering with sertoli cell glucose metabolism in mice

The growing global deterioration in several aspects of human health has been partly attributed to hazardous effects of endocrine-disrupting chemicals (EDCs) exposure. Therefore, experts and government regulatory agencies have consistently advocated for studies on the combined effects of EDCs that model human exposure to multiple environmental chemicals in real life. Here, we investigated how low concentrations of bisphenol A (BPA), and phthalates compounds affect the Sertoli cell glucose uptake/lactate production in the testis and male fertility. An EDC mixture containing a detected amount of each chemical compound in humans, called daily exposure (DE), and DE increased in magnitude by 25 (DE25), 250 (DE250), and 2500 (DE2500), and corn oil (control) were administered for six weeks to male mice. We found that DE activated estrogen receptor beta (Erβ) and glucose-regulated protein 78 (Grp 78) and disrupted the estradiol (E2) balance. In addition, DE25, DE250, and DE2500 doses of the EDC mixture via binding with Sertoli cells’ estrogen receptors (ERs) inhibited the glucose uptake and lactate production processes by downregulating glucose transporters (GLUTs) and glycolytic enzymes. As a result, endoplasmic reticulum stress (ERS), marked by unfolded protein response (UPR) activation, was induced. The accompanying upregulation of activating transcription factor 4 (ATF4), inositol requiring enzyme-1 (IRE1), C/EBP homologous protein (CHOP), and mitogen-activated protein kinase (MAPK) signaling promoted antioxidant depletion, testicular cell apoptosis, abnormal regulation of the blood−testis barrier, and decreased sperm count. Therefore, these findings suggest that human and wildlife exposure to multiple environmental chemicals can produce a wide range of reproductive health complications in male mammals.