The Effect of Lanthanum (III) Nitrate on the Osteogenic Differentiation of Mice Bone Marrow Stromal Cells.

To study the species of lanthanum (III) nitrate (La[NO3]3) dispersed in cell media and the effect on the osteoblast differentiation of bone marrow stroma cells (BMSCs). Different La-containing precipitations were obtained by adding various concentrations of La(NO3)3 solutions to Dulbecco's modified Eagle medium (DMEM) or DMEM with fetal bovine serum (FBS). A series of characterisation methods, including dynamic light scattering, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and protein quantification were employed to clarify the species of the different La-containing precipitations. The primary BMSCs were isolated, and the cell viability, alkaline phosphatase activity, and the formation of a mineralised nodule of BMSCs were tested when treated with different La-containing precipitations. The La(NO3)3 solutions in DMEM could form LaPO4, which exits in the particle formation, while the La(NO3)3 solutions in DMEM with FBS could form a La-PO4-protein compound. When treated with La(NO3)3 solutions in DMEM, the cell viability of the BMSCs was inhibited at the concentrations of 1, 10, and 100 µM at 1 day and 3 days. Meanwhile, the supernatant derived from the La(NO3)3 solutions in DMEM did not affect the cell viability of the BMSCs. In addition, the precipitate derived from the La(NO3)3 solutions in DMEM added to the complete medium inhibited the cell viability of the BMSCs at concentrations of 10 µM and 100 µM. When treated with La(NO3)3 solutions in DMEM with FBS, the derived precipitate and supernatant did not affect the cell viability of the BMSCs, except for the concentration of 100 µM La(NO3)3. The La-PO4-protein formed from the La(NO3)3 solutions in DMEM with FBS inhibited the osteoblast differentiation of BMSCs at the concentration of 1 µM La(NO3)3 (P < 0.05) but had no effect on either the osteoblast differentiation at the concentrations of 0.001 and 0.1 µM or on the formation of a mineralised nodule at all tested concentrations of La(NO3)3. Overall, La(NO3)3 solutions in different cell culture media could form different La-containing compounds: La-PO4 particles (in DMEM) and a La-PO4-protein compound (in DMEM with FBS). The different La-containing compounds caused different effects on the cell viability, osteoblast differentiation, and the formation of a mineralised nodule of the BMSCs. The La-containing precipitation inhibited the osteoblast differentiation by inhibiting the expression of osteoblast-related genes and proteins, providing a theoretical basis for clinical doctors to apply phosphorus-lowering drugs such as lanthanum carbon.

The deposition of lanthanum carbonate may activate macrophages to induce gastrointestinal mucosal injury in patients with chronic kidney disease: an in vitro caco-2/THP-1 macrophage coculture model study.

The aim of this study was to investigate the effect and possible underlying mechanism of La2(CO3)3 deposition on GI mucosal inflammation. Our results showed that La2(CO3)3 can dissolve in artificial gastric fluids and form lanthanum phosphate (LaPO4) precipitates with an average size of about 1 µm. To mimic the intestinal mucosa and epithelial barrier, we established a Caco-2/THP-1 macrophage coculture model and a Caco-2 monoculture model, respectively. Our findings demonstrated that the medium of THP-1 macrophages stimulated by LaPO4 particles can damage the Caco-2 monolayer integrity in the coculture model, while the particles themselves had no direct impact on the Caco-2 monolayer integrity in the monoculture model. We measured values of trans-epithelial electrical resistance and detected images using a laser scanning confocal microscope. These results indicate that continuous stimulation of LaPO4 particles on macrophages can lead to a disruption of intestinal epithelium integrity. In addition, LaPO4 particles could stimulate THP-1 macrophages to secrete both IL-1ß and IL-8. Although LaPO4 particles can also promote Caco-2 cells to secrete IL-8, the secretion was much lower than that produced by THP-1 macrophages. In summary, the deposition of La2(CO3)3 has been shown to activate macrophages and induce damage to intestinal epithelial cells, which may exacerbate inflammation in patients with chronic kidney disease. Therefore, patients taking lanthanum carbonate, especially those with gastrointestinal mucosal inflammation, should be mindful of the potential for drug deposition in the GI system.

Multienzyme-Mimicking LaCoO3 Nanotrigger for Programming Cancer-Cell Pyroptosis.

Pyroptosis, a distinct paradigm of programmed cell death, is an efficient strategy against cancer by overcoming resistance to apoptosis. In this study, LaCoO3 (LCO) lanthanide-based nanocrystals with multienzyme characteristics are rationally designed and engineered to trigger the generation of cytotoxic reactive oxygen species (ROS) and the release of lanthanum ions, ultimately inducing lung cancer cell pyroptosis. The peroxidase- and oxidase-mimicking activities of LCO nanocrystals endow LCO with ROS production capacity in tumor tissues with an acidic pH and high hydrogen peroxide content. Concurrently, the LCO nanoenzyme exhibits catalase- and glutathione peroxidase-like activities, reversing the hypoxic microenvironment, destroying the activated antioxidant system of tumor cells, and amplifying the sensitivity of tumor cells to ROS. The use of ultrasound further accelerates the enzymatic kinetic rate. Most importantly, the La3+ ions released by LCO robustly destroy the lysosomal membrane, finally inducing canonical pyroptotic cell death, together with ROS. LCO-nanocrystal-triggered programmed cell pyroptosis amplifies the therapeutic effects both in vitro and in vivo, effectively restraining lung cancer growth and metastasis. This study paves a new avenue for the efficient treatment of lung cancer and metastasis through US-enhanced lanthanum-based nanoenzyme platforms and pyroptotic cell death.

[The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9].

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.

Regulatory actions of rare earth elements (La and Gd) on the cell cycle of root tips in rice seedlings (Oryza sativa L.).

The continuous expansion of the application of rare earth elements (REEs) in various fields has attracted attention to their biosafety. At present, the molecular mechanisms underlying the biological effects of REEs are unclear. In this study, the effects of lanthanum (La) and gadolinium (Gd) on cell cycle progression in the root tips of rice seedlings were investigated. Low concentrations of REEs (0.1 mg L-1) induced an increase in the number of cells in the prophase and metaphase, while high concentrations of REEs (10 mg L-1) induced an increase in the number of cells in the late and terminal stages of the cell cycle, and apoptosis or necrosis. Additionally, low concentrations of REEs induced a significant increase in the expression of the cell cycle factors WEE1, CDKA;1, and CYCB1;1, and promoted the G2/M phase and accelerated root tip growth. However, at high REEs concentrations, the DNA damage response sensitized by BRCA1, MRE11, and TP53 could that prevent root tip growth by inhibiting the transcription factor E2F, resulting in obvious G1/S phase transition block and delayed G2/M phase conversion. Furthermore, by comparing the biological effect mechanisms of La and Gd, we found that these two REEs share regulatory actions on the cell cycle of root tips in rice seedlings.

Action of the Nrf2/ARE signaling pathway on oxidative stress in choroid plexus epithelial cells following lanthanum chloride treatment.

Lanthanum (La) can damage the blood brain barrier when it enters the brain tissue, causing learning and memory dysfunction. Currently, few studies have focused on La-induced oxidative stress in choroid plexus epithelial cells, which can severely impair the normal function of the blood-cerebrospinal fluid barrier (BCSFB) and ultimately cause central nervous system dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element(ARE) signaling pathway is one of the major antioxidant systems and is vital in protecting cells against oxidative injury in rodents. In this study, Z310 cells were employed to construct BCSFB in vitro and treated with lanthanum chloride (LaCl3); meanwhile, 40 µmol/L tert-butylhydroquinone and the corresponding concentration of LaCl3 was used as the intervention groups. The results showed that LaCl3 treatment markedly decreased Z310 cell viability, increased the necrosis rate, and then reduced the transepithelial electrical resistance value of BCSFB in vitro; reactive oxygen species levels gradually increased, catalase and glutathione peroxidase activities decreased; furthermore, Nrf2 was significantly downregulated, and the expression of Nrf2 downstream genes such as heme oxygenase1, NADP(H): dehydrogenase quinone1, glutathione thiotransferase etc. noticeably decreased; in addition, interleukin-1ß and tumour necrosis factor-α associated with Nrf2 activation noticeably increased. However, tert-butylhydroquinone could activate the Nrf2/AER signaling pathway and attenuate the Z310 cell oxidative damage induced by LaCl3. Thus, the Nrf2/ARE signaling pathway is probably involved in weakening the BCSFB in vitro that is created by La-induced oxidative stress. Tert-butylhydroquinone can activate this pathway to reverse severe oxidative damage, which significantly strengthen the function of BCSFB.

Biological applications of green synthesized lanthanum oxide nanoparticles via Couroupita guianensis abul leaves extract.

In this work, extract from leaves of Couroupita guianensis (C.guianensis) abul was used as a potential reducing agent for the synthesis of lanthanum oxide (La2O3) nanoparticles (NPs). In addition, the morphology and several physicochemical properties of the La2O3 NPs were improved by introducing the ionic liquid of 1-butyl 3-methyl imidazolium tetra fluoroborate (BMIM BF4) as a stabilizing agent. The structure of the La2O3 (without ionic liquid) and IL-La2O3 (with ionic liquid) NPs were analyzed by X-ray diffraction (XRD). The chemical composition of the synthesized NPs was analyzed using the energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) studies. Optical and morphological studies were also performed. The antibacterial, antioxidant, anti-inflammatory, anti-diabetic and anticancer properties of the La2O3 and IL-La2O3 NPs were evaluated.

Hyperthermia and doxorubicin release by Fol-LSMO nanoparticles induce apoptosis and autophagy in breast cancer cells.

Background: Studies on the anticancer effects of lanthanum strontium manganese oxide (LSMO) nanoparticles (NPs)-mediated hyperthermia at cellular and molecular levels are scarce. Materials & methods: LSMO NPs conjugated with folic acid (Fol-LSMO NPs) were synthesized, followed by doxorubicin-loading (DoxFol-LSMO NPs), and their effects on breast cancer cells were investigated. Results: Hyperthermia (45°C) and combination treatments exhibited the highest (∼95%) anticancer activity with increased oxidative stress. The involvement of intrinsic mitochondria-mediated apoptotic pathway and induction of autophagy was noted. Cellular and molecular evidence confirmed the crosstalk between apoptosis and autophagy, involving Beclin1, Bcl2 and Caspase-3 genes with free reactive oxygen species presence. Conclusion: The study confirmed hyperthermia and doxorubicin release by Fol-LSMO NPs induces apoptosis and autophagy in breast cancer cells.

Bi-directional regulation functions of lanthanum-substituted layered double hydroxide nanohybrid scaffolds via activating osteogenesis and inhibiting osteoclastogenesis for osteoporotic bone regeneration.

Rationale: Osteoporotic patients suffer symptoms of excessive osteoclastogenesis and impaired osteogenesis, resulting in a great challenge to treat osteoporosis-related bone defects. Based on the positive effect of rare earth elements on bone metabolism and bone regeneration, we try to prove the hypothesis that the La3+ dopants in lanthanum-substituted MgAl layered double hydroxide (La-LDH) nanohybrid scaffolds simultaneously activate osteogenesis and inhibit osteoclastogenesis. Methods: A freeze-drying technology was employed to construct La-LDH nanohybrid scaffolds. The in vitro osteogenic and anti-osteoclastogenic activities of La-LDH nanohybrid scaffolds were evaluated by using ovariectomized rat bone marrow stromal cells (rBMSCs-OVX) and bone marrow-derived macrophages (BMMs) as cell models. The in vivo bone regeneration ability of the scaffolds was investigated by using critical-size calvarial bone defect model of OVX rats. Results: La-LDH nanohybrid scaffolds exhibited three-dimensional macroporous structure, and La-LDH nanoplates arranged perpendicularly on chitosan organic matrix. The La3+ dopants in the scaffolds promote proliferation and osteogenic differentiation of rBMSCs-OVX by activating Wnt/ß-catenin pathway, leading to high expression of ALP, Runx-2, COL-1 and OCN genes. Moreover, La-LDH scaffolds significantly suppressed RANKL-induced osteoclastogenesis by inhibiting NF-κB signaling pathway. As compared with the scaffolds without La3+ dopants, La-LDH scaffolds provided more favourable microenvironment to induce new bone in-growth along macroporous channels. Conclusion: La-LDH nanohybrid scaffolds possessed the bi-directional regulation functions on osteogenesis and osteoclastogenesis for osteoporotic bone regeneration. The modification of La3+ dopants in bone scaffolds provides a novel strategy for osteoporosis-related bone defect healing.

Ligand-Sensitised LaF3 :Eu3+ and SrF2 :Eu3+ Nanoparticles and in Vitro Haemocompatiblity Studies.

Luminescent Ln3+ -doped nanoparticles (NPs) functionalised with the desired organic ligand molecules for haemocompatibility studies were obtained in a one-pot synthesis. Chelated aromatic organic ligands such as isophthalic acid, terephthalic acid, ibuprofen, aspirin, 1,2,4,5-benzenetetracarboxylic acid, 2,6-pyridine dicarboxylic acid and adenosine were applied for surface functionalisation. The modification of the nanoparticles is based on the donor-acceptor character of the ligand-nanoparticle system, which is an alternative to covalent functionalisation by peptide bonding as presented in our recent report. The aromatic groups of selected ligands absorb UV light and transfer their excited-state energy to the dopant Eu3+ ions in LaF3 and SrF2 NPs. Herein, we discuss the structural and spectroscopic characterisation of the NPs and the results of haemocompatibility studies. Flow cytometry analysis of the nanoparticles' membrane-binding is also presented.

Lanthanum delays senescence and improves postharvest quality in cut tulip (Tulipa gesneriana L.) flowers.

We tested two sources of lanthanum (La), LaCl3 and La(NO3)3 × 6H2O at a concentration of 40 µM each, in the treatment solution of cut flowers of 15 tulip (Tulipa gesneriana L.) cultivars. Ascorbic acid (AsA; 0.2 g/L) was used as a reference solution, while distilled water was evaluated as an absolute control. With both La sources, bud length and diameter, and stem length were increased; as a result, stem curvature was also significantly increased with La treatments. The cultivars Laura Fygi and Rosario registered the highest relative stem elongation. Lalibela and Acropolis displayed the greatest stem curvature on the last day in vase. At 3, 5, 7, 9 and 11 days after cutting, the highest solution uptake was recorded in flower stems treated with LaCl3, surpassing the control by 5, 11, 15, 18 and 24%, respectively. The relative stem elongations observed were 21.3, 27.4, 35.2 and 35.5% in the control, AsA, LaCl3 and La(NO3)3, respectively. The mean solution uptake per gram of stem fresh biomass weight was 1.44, 1.44, 1.71 and 1.54 mL in the control, AsA, LaCl3 and La(NO3)3, respectively. LaCl3 significantly increased the bud length and solution uptake of flower stems, while La(NO3)3 × 6H2O increased stem fresh weight.

Magnetic lanthanum-doped hydroxyapatite/chitosan scaffolds with endogenous stem cell-recruiting and immunomodulatory properties for bone regeneration.

Generally, the addition of exogenous stem cells and host-to-scaffold immune responses restricts the clinical applications of hydroxyapatite (HA)/chitosan (CS) scaffolds for bone regeneration. To achieve "facilitated endogenous tissue engineering", magnetic M-type hexagonal ferrite (SrFe12O19) nanoparticles were incorporated into bone scaffolds to recruit endogenous stem cells. Then, lanthanum incorporation was utilized to regulate host-to-scaffold immune responses and to provide a pro-regenerative environment for recruited endogenous stem cells. Here, we first fabricated and characterized magnetic lanthanum-doped HA/CS scaffolds. The MLaHA/CS scaffolds were demonstrated to be effective at recruiting rat bone marrow mesenchymal stem cells (rBMSCs) and modulating host-to-scaffold immune responses by promoting macrophage polarization into the anti-inflammatory phenotype (M2) in vitro. By further examining the underlying mechanism, we found that MLaHA/CS scaffolds could promote the osteogenic differentiation of rBMSCs by upregulating the phosphorylation of the Smad 1/5/9 pathway. When MLaHA/CS scaffolds were implanted into rat calvarial defects, the incorporation of magnetic nanoparticles and lanthanum significantly promoted the new bone regeneration, as revealed by micro-CT assays and histological staining. Our findings suggest that MLaHA/CS shows great potential for use as a cell-free and biocompatible scaffold for bone regeneration.

Calcium alginate template-mineral substituted hydroxyapatite hydrogel coated titanium implant for tibia bone regeneration.

Osteogenic differentiation is great significance for improving the bone regeneration. Present study evaluates the osteogenic ability of lanthanum (La3+) and silicate (SiO44-) substituted hydroxyapatite (MHAP) - polymeric composite coated surface treated titanium (Ti) implant. The bio-ceramic MHAP was synthesized by hydrothermal process with assistance of calcium alginate template. For enhance the hydrophilicity, the polymer poly (vinyl pyrrolidone) (PVP) was included in the composite by ultra-sonication method. The negative zeta potential value -9.97 mV of Ca-alg/ La, Si-HAP was observed after the incorporation of PVP in the matrix. Incorporation of minerals and PVP polymer was confirmed and analyzed by Energy Dispersive X-ray analysis (EDX), Fourier Transform Infra-Red spectroscopy (FT-IR) and Electron Microscopy techniques. A compact coating of the composite with the thickness of 448 nm on Ti surface was achieved by Electrophoretic deposition (EPD) method. The in-vitro MTT assay method and alkaline phosphate ALP activity (94% and 0.94 a.u respectively for the optimized composite) were utilized to determine the cell viability and differentiation on human Bone Marrow-Derived Stem Cells (hBMSCs). The osteogenic ability of bio-composite coated Ti in hBMSCs and in-vivo rat model has strongly suggests the fabricated Ti plate with bio-composite coatings can act as promising biomaterial for orthopedics.

Intratumoral inorganic phosphate deprivation: A new anticancer strategy?

Tumor epidemiology, as well as tumor microenvironments and cancer cell signaling study, has been presented with statistical relevance of inorganic phosphate (Pi) to tumorigenesis. Although serum Pi is still not acknowledged as a clinical tumor biomarker, abnormally high Pi concentration in serum or tumor lesions is gradually recognized as a characteristic of malignancy. On the other hand, phosphate binder (e.g. La2 (CO3)3, Fosrenols) has been clinically approved to treat hyperphosphatemia, a metabolic disease characterized by a high serum phosphate level. We hypothesize that, if reducing phosphate burden comes to benefit tumor therapy, could systemic or intratumoral administration of phosphate binder effectively deprive tumor Pi concentration, and then inhibit tumor growth and metastases? From the past clinical and preclinical outcomes, we'd conclude that Pi is not only a metabolite during tumor growth but also a force to trigger tumor progression and metastases. Two types of cancer models were developed to initiate this study. Firstly, a patient-derived xenograft mouse model of colorectal cancer was designed, where mice were administered systemically or intratumorally with lanthanum acetate (a molecular phosphate binder), and the serum or intratumoral Pi concentration levels were found to a dropdown. Secondly, a rabbit VX2 liver tumor was set up for the local-regional therapy model, where lanthanum acetate was intratumorally administered by the standard transcatheter arterial chemoembolization procedure, and it significantly reduced intratumoral Pi concentration. Therefore, Pi deprivation by phosphate binder might be a new anticancer strategy if reducing phosphate burden could effectively arrest tumor growth and delay metastatic progression.

One-pot synthesis of Ln3+-doped porous BiF3@PAA nanospheres for temperature sensing and pH-responsive drug delivery guided by CT imaging.

The design and synthesis of responsive inorganic nanocapsules have attracted intensive research interest in cancer treatment. The combination of non-invasive diagnosis and chemotherapy into a single theranostic nanoplatform is prospective in the biomedical field. In this work, a polyacrylic acid (PAA)-functionalized porous BiF3:Yb,Er nanocarrier was constructed via a straightforward one-pot solvothermal strategy. Compared with the undoped BiF3 sub-microspheres, the lanthanide ion (Ln3+) doping endowed the BiF3 material with a smaller size and increased BET specific surface area and pore volume, which make it suitable as a drug carrier. It was found that the synthesized nanomaterial could effectively relieve the side effects of doxorubicin (DOX) and exhibited pH-dependent DOX loading and release. Its satisfactory biocompatibility and efficient tumor inhibition were emphasized by a series of in vitro/in vivo experiments. In addition, the synthesized nanomaterial exhibited favorable CT contrast efficacy due to the excellent X-ray attenuation coefficient of Bi. Moreover, characteristic upconversion luminescence and temperature sensing in a wide temperature range were realized over the synthesized BiF3:Yb,Er sample. Therefore, carboxyl-functionalized BiF3:Yb,Er can be expected to be an ideal candidate in the fabrication of temperature sensing and multifunctional theranostic nanoplatforms.

Lanthanum, Gallium and their Impact on Oxidative Stress.

The role metals play in living organisms is well established and subject to extensive research. Some of them participate in electron-exchange reactions. Such reactions cause generation of free radicals that can adversely impact biological systems, as a result of oxidative stress. The impact of 'non-biological' metals on oxidative stress is also a worthy pursuit due to the crucial role they play in modern civilization. Lanthanides (Ln) are widely used in modern technology. As a result, human exposure to them is increasing. They have a number of established medical applications and are being extensively researched for their potential antiviral, anticancer and anti-inflammatory properties. The present review focuses on lanthanum (La) and its impact on oxidative stress. Another metal, widely used in modern high-tech is gallium (Ga). In some respects, it shows certain similarities to La, therefore it is a subject of the present review as well. Both metals exhibit ionic mimicry which allows them to specifically target malignant cells, initiating apoptosis that makes their simple salts and coordination complexes promising candidates for future anticancer agents.

Turnip Mosaic Virus Is a Second Example of a Virus Using Transmission Activation for Plant-to-Plant Propagation by Aphids.

Cauliflower mosaic virus (CaMV; family Caulimoviridae) responds to the presence of aphid vectors on infected plants by forming specific transmission morphs. This phenomenon, coined transmission activation (TA), controls plant-to-plant propagation of CaMV. A fundamental question is whether other viruses rely on TA. Here, we demonstrate that transmission of the unrelated turnip mosaic virus (TuMV; family Potyviridae) is activated by the reactive oxygen species H2O2 and inhibited by the calcium channel blocker LaCl3 H2O2-triggered TA manifested itself by the induction of intermolecular cysteine bonds between viral helper component protease (HC-Pro) molecules and by the formation of viral transmission complexes, composed of TuMV particles and HC-Pro that mediates vector binding. Consistently, LaCl3 inhibited intermolecular HC-Pro cysteine bonds and HC-Pro interaction with viral particles. These results show that TuMV is a second virus using TA for transmission but using an entirely different mechanism than CaMV. We propose that TuMV TA requires reactive oxygen species (ROS) and calcium signaling and that it is operated by a redox switch.IMPORTANCE Transmission activation, i.e., a viral response to the presence of vectors on infected hosts that regulates virus acquisition and thus transmission, is an only recently described phenomenon. It implies that viruses contribute actively to their transmission, something that has been shown before for many other pathogens but not for viruses. However, transmission activation has been described so far for only one virus, and it was unknown whether other viruses also rely on transmission activation. Here we present evidence that a second virus uses transmission activation, suggesting that it is a general transmission strategy.

Lanthanum chloride induces autophagy in rat hippocampus through ROS-mediated JNK and AKT/mTOR signaling pathways.

Lanthanum (La) can cause central nervous system damage in rats and lead to learning and memory impairment, but the relevant mechanisms have not been fully elucidated. Autophagy is the self-balancing and self-renewal process of cells that degrades damaged macromolecules and organelles through the lysosomal pathway. It is an important mechanism to resist harmful stress, but excessive autophagy leads to type II programmed cell death. A variety of chemicals can induce oxidative stress, and a large number of reactive oxygen species (ROS) can regulate the level of autophagy through multiple signaling pathways. Our previous studies showed that La could cause oxidative stress, inhibit Nrf2/ARE signaling pathway and impair learning and memory, but it is unclear whether the mechanism is related to autophagic disorders of neurons. In this study, Wistar rats were exposed to 0% (w/v), 0.25%, 0.5% and 1.0% lanthanum chloride (LaCl3) through their mother and drinking water from the embryonic phase to 1 month after weaning, and then the subsequent experiments were performed. The results showed that LaCl3 impaired spatial learning and memory and avoidance conditioning in rats and induced an increase in ROS levels in hippocampal nerve cells, which up-regulated p-JNK, p-c-Jun, p-FoxO1, p-FoxO3a, Beclin1 and LC3B-II expression and down-regulated p-AKT, p-mTOR and p62 expression. Meanwhile, the number of autophagosomes in hippocampal neurons in the 1.0% LaCl3-treated group was significantly increased. These results indicate that La can activate the JNK/c-Jun and JNK/FoxOs signaling pathways, inhibit the AKT/mTOR signaling pathway by inducing oxidative stress, and enhance autophagy in the hippocampus. This study suggests that the mechanism of learning and memory impairment induced by LaCl3 may be related to excessive autophagy.

Anti-cancer study and whey protein complexation of new lanthanum(III) complex with the aim of achieving bioactive anticancer metal-based drugs.

In this study, a new lanthanum (III)-amino acid complex utilizing cysteine has been synthesized and characterized. The anticancer activities of the prepared La(III) complex against MCF-7 cell lines were studied. Results of MTT assay showed that at all three incubation times, the cytotoxic effect of prepared La(III) complex on MCF-7 breast cancer cell lines displays a time- and dose-dependent inhibitory effects. The interactions of the La(III) complex with two whey proteins (bovine serum albumin, BSA, and Bovine ß-lactoglobulin, ßLG) have been explored by using spectroscopic and molecular dicking methods. The obtained results indicated that La(III) complex strongly quenched the fluorescence of two carrier proteins in static quenching mode and also, BSA hah stronger binding affinity toward studied complex than ßLG whit binding constant values of KBSA-La Complex ∼ 0.11 × 104 M-1 and KßLG-La Complex ∼ 0.63 × 103 M-1 at 300 K. The thermodynamic parameters revealed the contribution of hydrogen bond and Vander Waals interactions in both systems. The distances of the La(III) complex whit whey proteins were calculated using Förster energy transfer theory and proved existence of the energy transfer between two proteins and prepared La(III) complex with a high probability. FT-IR and UV-Vis absorption measurements indicated that the binding of the La(III) to BSA and ßLG may induce conformational and micro-environmental changes of the proteins. The docking results indicate that the La(III) complex bind to residues located in the site II of BSA and second site of ßLG. Communicated by Ramaswamy H. Sarma.