Amanda Martins Dionisio

Zinc oxide nanoparticles (ZnO NPs) are promising tools for improving Zn delivery to plants, but their efficiency depends strongly on their physicochemical properties. Here, we compared four ZnO NP formulations differing in origin, particle size and surface charge for their short-term interactions with Arabidopsis thaliana roots. Seedlings were exposed to 2.5–25 mg/L ZnO NPs for 2 h, and root Zn-associated fluorescence was visualized using ZinPyr-1. All formulations increased fluorescence in a concentration-dependent manner, but positively charged, chemically synthetized ZnO NPs (CHEM1, CHEM2) were more effective than negatively charged formulations. CHEM2, which is larger and less positive than CHEM1, induced the strongest response, particularly in the root tip and middle root zone, and produced a distinct Zn-associated signal in vascular tissues. No significant increase was detected near the root–shoot junction, indicating limited redistribution during short-term exposure. Plant exposure also altered suspension chemistry. In case of CHEM2, it caused the strongest acidification and Zn depletion, although changes in suspension Zn did not consistently correspond to root fluorescence or pH. These findings demonstrate that Zn delivery from ZnO NPs is highly formulation-dependent and likely reflects the combined influence of surface charge, particle size, dissolution and root–particle interactions. Thus, physicochemical properties should be carefully considered when designing ZnO nanomaterials for plant Zn delivery.

Background/Objectives: Fructose-1,6-bisphosphate (FBP) is an intermediate product of the glycolytic pathway with analgesic effect in acute inflammatory pain model via the production of adenosine. However, whether FBP is active in neuropathic pain is unknown. Therefore, we reason that it would be suitable to investigate the analgesic effect and mechanism of action of FBP in a model of chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain in mice. Methods: After CCI induction, mice received FBP, adenosine, A1 and/or A2A receptor antagonists, and/or inhibitors of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/ATP sensitive K channels (KATP) signaling pathway. Results: FBP (up to 85%) and adenosine (up to 84%) inhibited the mechanical hyperalgesia (electronic aesthesiometer) induced by CCI with similar profiles. FBP analgesia was dependent on adenosine because adenosine A1 and A2A receptors antagonists diminished FPB activity (100% and 79%, respectively). FBP analgesia was also dependent on activating the NO/cGMP/PKG/KATP signaling pathway. Furthermore, FBP treatment increased the production of NO in cultured dorsal root ganglia (DRG) neurons (100% increase), whereas neuronal nitric oxide synthase (nNOS) inhibition decreased (up to 70%) the analgesic effect of FBP. We also observed that FBP reduced the calcium levels of transient receptor potential ankyrin 1 (TRPA1)⁺ DRG neurons (85%) and paw-flinching triggered by TRPA1 activation (38%). Conclusions: FBP reduced neuropathic pain by reducing DRG neuron activation. The mechanisms involved the activation of adenosine A1 and A2A receptors to trigger the analgesic NO/cGMP/PKG/KATP signaling pathway and reducing TRPA1⁺ DRG neuron activity.

Understanding the strategies of delivering active ingredients with nanoparticles to plant species is crucial to implement a safe-by-design approach for pesticides. Here, we used metribuzin (MTZ) as a study model to understand the plant uptake and distribution pathways of polymeric nanocarriers. We investigated the weed-control efficacy, uptake, internalization, and distribution of the (nano) herbicide MTZ in Amaranthus viridis (C4 species) and Bidens pilosa (C3 species) after soil and foliar application. A radiolabeled herbicide and a fluorescent probe were used as complementary tools to track both MTZ and nanoparticles in plants. The weed-control results indicated significant dose reductions with MTZ nanoencapsulation (from 1/2 to 10-fold doses). Root uptake was an efficient pathway for A. viridis and the B. pilosa entry of nanoMTZ occurred preferentially in the stomata and was internalized in leaf mesophyll cells. No differences in herbicide uptake were observed in the soil, and the nanoMTZ distribution was 1.3–1.5 lower than MTZ. After foliar application, nanoMTZ was absorbed 2.5 times more than MTZ in A. viridis and was similar in B. pilosa. NPs were concentrated in the vascular cells after soil application and in the stomata entrance after foliar application. For B. pilosa, the internalization in the leaf mesophyll was more evident than that in A. viridis. Our findings indicated that consideration of the target weed species and application mode will increase the efficacy of control using nanoformulations.

Chikungunya virus is an arthropod-borne infectious agent that causes Chikungunya fever disease. About 90% of the infected patients experience intense polyarthralgia, affecting mainly the extremities but also the large joints such as the knees. Chronic disease symptoms persist for months, even after clearance of the virus from the blood. Envelope proteins stimulate the immune response against the Chikungunya virus, becoming an important therapeutic target. We inactivated the Chikungunya virus (iCHIKV) and produced recombinant E2 (rE2) protein and three different types of anti-rE2 monoclonal antibodies. Using these tools, we observed that iCHIKV and rE2 protein induced mechanical hyperalgesia (electronic aesthesiometer test) and thermal hyperalgesia (Hargreaves test) in mice. These behavioral results were accompanied by the activation of dorsal root ganglia (DRG) neurons in mice, as observed by calcium influx. Treatment with three different types of anti-rE2 monoclonal antibodies and absence or blockade (AMG-9810 treatment) of transient receptor potential vanilloid 1 (TRPV1) channel diminished mechanical and thermal hyperalgesia in mice. iCHIKV and rE2 activated TRPV1+ mouse DRG neurons in vitro, demonstrating their ability to activate nociceptor sensory neurons directly. Therefore, our mouse data demonstrate that targeting E2 CHIKV protein with monoclonal antibodies and inhibiting TRPV1 channels are reasonable strategies to control CHIKV pain.

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO₂) that trigger an immune response in the periprosthetic tissue, leading to arthritis, arthroplasty failure, and the need for revision. Flavonoids belong to a class of natural polyphenolic compounds that possess antioxidant and anti-inflammatory activities. Hesperidin methyl chalcone’s (HMC) analgesic, anti-inflammatory, and antioxidant effects have been investigated in some models, but its activity against the arthritis caused by prosthesis-wearing molecules, such as TiO₂, has not been investigated. Mice were treated with HMC (100 mg/kg, intraperitoneally (i.p.)) 24 h after intra-articular injection of 3 mg/joint of TiO₂, which was used to induce chronic arthritis. HMC inhibited mechanical hyperalgesia, thermal hyperalgesia, joint edema, leukocyte recruitment, and oxidative stress in the knee joint (alterations in gp91^phox, GSH, superoxide anion, and lipid peroxidation) and in recruited leukocytes (total reactive oxygen species and GSH); reduced patellar proteoglycan degradation; and decreased pro-inflammatory cytokine production. HMC also reduced the activation of nociceptor-sensory TRPV1⁺ and TRPA1⁺ neurons. These effects occurred without renal, hepatic, or gastric damage. Thus, HMC reduces arthritis triggered by TiO₂, a component released upon wearing of prosthesis.