The effect of bisphenols on sex and thyroid hormone concentrations in cord blood among newborns.

This study aims to investigate the associations of bisphenols with sex and thyroid hormones in cord blood among newborns. Four bisphenols, three hormones related to gonadal function, and four parameters related to thyroid function were measured in umbilical cord blood in 378 mother-newborn pairs. Multivariable linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression were used. In the multivariable linear regression, bisphenol A (BPA) was associated with increased testosterone (TT) (regression coefficient, ß = 0.049, 95% confidence interval, CI: 0.013,0.085; p = 0.007) and free tri-iodothyronine (FT3) levels (ß = 0.019, 95% CI: 0.003, 0.035; p = 0.023), and decreased thyroid peroxidase antibody (TPOAb) (ß = -0.053, 95% CI: 0.098, -0.008; p = 0.021). Consistently associations were observed in males, except TT, which was observed in females, and bisphenol AF (BPAF) was associated with decreased follicle-stimulating hormone (FSH) in females. These associations were also observed in a mixture of bisphenols. Moreover, we observed maternal prepregnancy body mass index (BMI) and delivery mode disparity in the relationship between bisphenols and sex and thyroid hormones. This study suggests that bisphenols may exert effects on sex and thyroid hormones in newborns, the effect may vary with sex differences, maternal prepregnancy BMI, and delivery mode.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Proteomic changes of the bilateral M1 and spinal cord in hemiplegic cerebral palsy mouse: Effects of constraint-induced movement therapy.

Hemiplegic cerebral palsy (HCP) is a non-progressive movement and posture disorder that affects one side of the body. Constraint-induced movement therapy (CIMT) can improve the hand function of children with HCP. We used label-free proteomic quantification technology to evaluate proteomic changes in the bilateral M1 and spinal cord in HCP mouse induced by hypoxia/ischemia and CIMT. Nissl staining showed reduced neuron density in the HCP mice's lesioned and contralesional M1. The rotarod test and grip strength test showed motor dysfunction in mice with HCP and improved motor ability after CIMT. A total of 5147 proteins were identified. Fifty-one, five, and sixty common differentially expressed proteins (DEPs), which were co-regulated by HCP and CIMT, were found in the lesioned M1, the contralesional M1 and the spinal cord respectively. The significant proteins included alpha-centractin, metaxin complex, PKC, septin 11, choline transporter-like proteins, protein 4.1, teneurin-4, and so on, which mainly related to synapse stability, neuronal development and maintenance, axon development, and myelin formation. The KEGG pathways of HCP-induced DEPs mainly related to lipid metabolism, synaptic remodeling, SNARE interactions in vesicular transport and axon formation. The CIMT-induced DEPs were mainly related to synaptic remodeling and axon formation in the lesioned M1 and spinal cord. This study investigated the proteomic changes of the bilateral M1 and spinal cord as well as the CIMT-induced proteomic changes in HCP mice, which might provide new insights into the therapy of HCP.

Constraint therapy promotes motor cortex remodeling and functional improvement by regulating c-Jun/miR-182-5p/Nogo - A signals in hemiplegic cerebral palsy mice.

BACKGROUND: Our previous study has confirmed that constraint-induced movement therapy (CIMT) could promote neural remodeling in hemiplegic cerebral palsy (HCP) mice through Nogo-A/NgR/RhoA/ROCK signaling, however, the upstream mechanism was still unclear. Therefore, the present study aimed to further explore the mechanism of CIMT regulating the expression of Nogo-A in HCP mice. METHOD: HCP mice were well established through ligating the left common carotid artery of 7-day-old pups and being placed in a hypoxic box which was filled with a mixture of 8% oxygen and 92% nitrogen. CIMT intervention was conducted by taping to fix the entire arm of the contralateral side (left) to force the mice to use the affected limb (right). Bioinformatics prediction and luciferase experiment were performed to confirm that miR-182-5p was targeted with Nogo-A. The beam test and grip test were applied to examine the behavioral performance under the intervention of c-Jun and CIMT. Also, immunofluorescence, Golgi staining, and transmission electron microscopy were conducted to show that the lenti-expression of c-Jun could increases the expression of myelin, and downregulates the expression of Nogo-A under the CIMT on HCP mice. RESULT: (1) The beam walking test and grip test experiment results showed that compared with the control group, the HCP + nCIMT group's forelimb grasping ability and balance coordination ability were decreased (P < 0.05). (2) The results of Golgi staining, and transmission electron microscopy showed that the thickness of myelin sheath and the density of dendritic spines in the HCP + nCIMT group were lower than those in the control group (P < 0.05). Compared with the HCP + nCIMT group, the cerebral cortex myelin sheath thickness, dendrite spine density and nerve filament expression were increased in HCP + CIMT group (P < 0.05). (3) Immunofluorescence staining showed that the expression of Nogo-A in the cerebral cortex of the HCP + nCIMT group was higher than that of the HCP + CIMT group (P < 0.05). Compared with the HCP + CIMT group, the expression of Nogo-A in the HCP + LC + CIMT group was decreased and, in the HCP, + SC + CIMT group was significantly increased (P < 0.05). Compared with the HCP + nCIMT group, the expression of c-Jun in the control, HCP + CIMT, HCP + LC + nCIMT and HCP + LC + CIMT groups was significantly increased, and in the HCP + SC + CIMT was decreased (P < 0.05). (4) Real-time quantitative polymerase chain reaction (RT-qPCR) results showed that the expression level of miR-182-5p in the HCP + LC + CIMT group was more increased than that in the HCP + nCIMT group (P < 0.05). The expression level of miR-182-5p in the HCP + LC + CIMT group was higher than that in the HCP + LC + nCIMT group and the HCP + SC + CIMT group (P < 0.05). CONCLUSION: These data identified that CIMT might stimulate the remodeling of neurons and myelin in the motor cortex by partially inhibiting the c-Jun/miR-182-5p/Nogo-A pathway, thereby facilitating the grasping performance and balance function of HCP mice.

Diagnosing Balamuthia mandrillaris amebic meningoencephalitis in a 64-year-old woman from the Southwest of China.

Balamuthia mandrillaris amebic encephalitis (BAE) can cause a fatal condition if diagnosis is delayed or effective treatment is lacking. Patients with BAE have been previously reported in 12 provinces of China, with skin lesions being the primary symptom and encephalitis developing after several years. However, a significantly lower number of cases has been reported in Southwest China. Here we report an aggressive BAE case of a 64-year-old woman farmer with a history of skin lesions on her left hand. She was admitted to our hospital due to symptoms of dizziness, headache, cough, vomiting, and gait instability. She was initially diagnosed with syphilitic meningoencephalitis and received a variety of empirical treatment that failed to improve her symptoms. Finally, she was diagnosed with BAE combined with amebic pneumonia using next-generation sequencing (NGS), qRT-PCR, sequence analysis, and imaging studies. She died approximately 3 weeks after the onset. This case highlights that the rapid development of encephalitis can be a prominent clinical manifestation of Balamuthia mandrillaris infection.

Adverse events after different forms of botulinum neurotoxin A injections in children with cerebral palsy: An 8-year retrospective study.

AIM: To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations. METHOD: A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database. RESULTS: The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}] = 3.65 [1.56, 5.40], p < 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI] = 2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p < 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p > 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r = 0.36 and r = 0.27 respectively, p < 0.01). INTERPRETATION: Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors. WHAT THIS PAPER ADDS: The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.

Nutritional status and function after high-calorie formula vs. Chinese food intervention in undernourished children with cerebral palsy.

Aim: To investigate the efficacy and safety of high-calorie formula vs. Chinese daily food on the nutritional status and motor function of undernourished children with cerebral palsy (CP). Methods: In this prospective, assessor-blind, and randomized controlled trial, we recruited children (1-10 years) with CP and undernutrition based on the WHO and the American Society for Parenteral and Enteral Nutrition criteria from the National Children's Medical Center. Participants were randomly allocated (1:1) to a high-calorie formula group or a Chinese daily food diet group (control group) for 6 months. Indirect calorimetry was used to estimate energy requirements. We compared the nutritional status and gross motor function of participants in both groups based on weight, height, z-scores (weight-for-age, height-for-age, weight-for-height, and BMI-for-age), and the Gross Motor Function Measure (GMFM), respectively, at baseline, 3-, and 6-months follow-up. In addition, the effective rate of nutritional intervention, and adverse events were simultaneously assessed. Results: From July 2020 to December 2021, a total of 119 participants were enrolled and randomized, and 110 participants completed the study (with 54 children in the high-calorie formula group and 56 children in the control group). After 6 months of treatment, the weight, height, z-scores (weight-for-height, weight-for-age, and BMI-for-age), and GMFM of both groups were significantly improved (p < 0.05). There were significant differences in changes in weight, weight-for-age z-scores, and GMFM between the two groups (p < 0.05). During the study period, 16 children experienced at least one mild adverse event [9 (16.7%) in the formula group and 7 (12.5%) in the control group]. Conclusion: Nutritional intervention with a high-calorie formula may be an effective and safe option in children with CP for improving undernutrition and gross motor dysfunction. Clinical trial registration: www.chictr.org.cn, identifier: ChiCTR2000033878.

Safety and effects of transcranial direct current stimulation on hand function in preschool children with hemiplegic cerebral palsy: A pilot study.

Transcranial direct current stimulation (tDCS) has shown a promising prospect in improving function and spasticity in school-aged children with cerebral palsy, but little is known in preschool children. The aim of this study was to explore the safety and effects of tDCS on hand function in preschool children (aged 3-6 years) with hemiplegic cerebral palsy (HCP). We designed a crossover, single-blind, sham-controlled study in 30 preschool children with HCP, who were recruited to receive one session of sham and one session of active anodal tDCS (1.5 mA, 20 min) on the primary motor cortex of the affected hemisphere, with a 24-h interval between the two sessions. Questionnaire was completed by each participant and their attendants immediately, 90 min, and 24 h after each session to monitor common adverse events of tDCS, such as skin irritation, skin erythema, burning sensation, headache, dizziness, etc. Box and Block Test, Selective Control of the Upper Extremity Scale, Modified Ashworth Scale, and Melbourne Assessment 2 were conducted at baseline, immediately, and 90 min after each session. No severe adverse event occurred during the study and only a few of them felt transient and slight discomfort. Results also showed that all participants performed better at Box and Block Test of the hemiplegic hand immediately after a single anodal tDCS (P < 0.05) and this improvement lasted at least 90 min and more than 24 h. However, there was no significant improvement in Selective Control of the Upper Extremity Scale of both hands, Box and Block Test of the non-hemiplegic hand, Modified Ashworth Scale, and Melbourne Assessment 2 of the hemiplegic upper limb (P > 0.05). Shortly, this study supported the safety and effects of a single anodal tDCS on improving the manual dexterity of the hemiplegic hand for preschool children with HCP. Further researches with larger samples about the optimal dose and treatment cycle of tDCS for preschool children with HCP are warranted. This study gained the approval of ethics committee of the organization and was registered at chictr.org (ChiCTR2000031141).

Adverse reproductive and developmental consequences of quantum dots.

Quantum dots (QDs), with a size of 1-10 nm, are luminescent semiconductor nanocrystals characterized by a shell-core structure. Notably, QDs have potential application in bioimaging owing to their higher fluorescence performance than conventional fluorescent dyes. To date, QDs has been widely used in photovoltaic devices, supercapacitors, electrocatalysis, photocatalysis. In recent years, scientists have focused on whether the use of QDs can interfere with the reproductive and developmental processes of organisms, resulting in serious population and community problems. In this study, we first analyze the possible reproductive and development toxicity of QDs. Next, we summarize the possible mechanisms underlying QDs' interference with reproduction and development, including oxidative stress, altered gametogenesis and fetal development gene expression, autophagy and apoptosis, and release of metal ions. Thereafter, we highlight some potential aspects that can be used to eliminate or reduce QDs toxicity. Based on QDs' unique physical and chemical properties, a comprehensive range of toxicity test data is urgently needed to build structure-activity relationship to quickly evaluate the ecological safety of each kind of QDs.

The Release of Indium Ion Derived from Epithelial Cells and Macrophages Solubilization Contribute to Pneumotoxicity Induced by Indium Oxide Nanoparticles.

Occupational exposure to indium oxide and indium containing particles has been associated with the development of severe lung diseases called "indium lung." According to the survey of occupational hygiene, indium oxide nanoparticles have been identified in the workplaces and the lungs of workers. To date, the potential mechanism of the pneumotoxicity has been poorly understood and no effective therapies are available against "indium lung." Our present study reported that the exposure of indium oxide nanoparticles damaged lung epithelial cells and alveolar macrophages and induced pulmonary alveolar proteinosis and inflammation in rats. In the 8-week post-exposure period, the indium oxide nanoparticles still mostly accumulated in the lungs and then persistently release indium ions in two months after exposure. In vitro, the epithelial cells show the greater potential for release of indium ions from indium oxide nanoparticles compared with the macrophages. EDTA-2Na, a metal chelating agent expected to remove the indium ions, was found to significantly reduced the cytotoxicity of indium oxide nanoparticles. Herein, the pneumotoxicity may be attributed to the slow and incremental release of indium ions from indium oxide nanoparticles primary dissolved by epithelial cells and macrophages, at least partially. The study may provide some insights to the pathogenicity mechanisms of "indium lung" and some clues against the health hazards of occupational inhaled indium oxide nanoparticles at the workplaces.

Reproductive toxicity and underlying mechanisms of di(2-ethylhexyl) phthalate in nematode Caenorhabditis elegans.

DEHP (di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using DEHP concentrations of 10, 1, and 0.1 mg/L, we showed that DEHP reduced the reproductive capacity of Caenorhabditis elegans after 72 hr. of exposure. DEHP exposure reduced the reproductive capacity in terms of decreased brood sizes, egg hatchability (0.1, 1 and 10 mg/L), and egg-laying rate (1 and 10 mg/L), and increased numbers of fertilized eggs in the uterus (1 and 10 mg/L). DEHP also caused damage to gonad development. DEHP decreased the total number of germline cells, and decreased the relative area of the gonad arm of all exposure groups, with worms in the 1 mg/L DEHP exposure group having the minimum gonad arm area. Additionally, DEHP caused a significant concentration-dependent increase in the expression of unc-86. Autophagy and ROS contributed to the enhancement of DEHP toxicity in reducing reproductive capacity, and glutathione peroxidase and superoxide dismutase were activated as the antioxidant defense in this study. Hence, we found that DEHP has a dual effect on nematodes. Higher concentration (10 mg/L) DEHP can inhibit the expression of autophagy genes (atg-18, atg-7, bec-1, lgg-1 and unc-51), and lower concentrations (0.1 and 1 mg/L) can promote the expression of autophagy genes. Our data highlight the potential environmental risk of DEHP in inducing reproductive toxicity toward the gonad development and reproductive capacity of environmental organisms.

Exploration of the optimal strategy for dietary calcium intervention against the toxicity of liver and kidney induced by cadmium in mice: An in vivo diet intervention study.

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control.

A review on Cadmium Exposure in the Population and Intervention Strategies Against Cadmium Toxicity.

The rapid industrial development has led to serious cadmium (Cd) pollution. Cd is a toxic heavy metal placing severe health threat to human. Cd can enter the body through the atmosphere, water, soil and food, and has a long half-life (10-30 years), it largely accumulates in kidneys, liver, bone and other organs and causes irreversible damage to the target organs. Cd pollution has also further caused certain carcinogenic and non-carcinogenic health risk. This study summarizes the current situation of Cd pollution, the toxicity of specific target organs, carcinogenic risk and non-carcinogenic risk in the general population, as well as dietary supplements to prevent and mitigate Cd toxication, which aims to focus on the adverse effects of Cd to human from both individual and population perspectives, hoping that not only the health risk of Cd poisoning can be reduced, but also the accurate prevention and control of Cd poisoning can be achieved in the future.

Adverse health effects of lead exposure on physical growth, erythrocyte parameters and school performances for school-aged children in eastern China.

We conducted a cross-sectional study with 395 completely matched student samples enrolled from a public primary school in Nanjing of eastern China, including questionnaires, blood samples, growth indexes and school performances, all of which were used for the analysis of variance (ANOVA) and general linear model (GLM). The results showed that factors, such as gender, age, parents' education, residential passive smoking and picky eaters, had significant impacts on the blood lead levels (BPbs). As for the linear and non-linear dose-response relationship between BPbs and erythrocyte parameters, we found a positive association between BPbs and red blood cell count (RBC count) and mean corpuscular hemoglobin concentration (MCHC) but a negative association between BPbs and hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). When BPbs increased by 10 µg/L, the RBC count increased by 0.18 × 1012/L, while HGB and HCT decreased by 1.19 g/L and 0.41% for boys, respectively. As for girls, corresponding increases in RBC count was 0.05 × 1012/L, while HGB and HCT decreased by 0.82 g/L and 0.23%. Meanwhile, for both boys and girls, MCHC increased by 2.55 g/L, while MCV and MCH levels decreased by 0.41 fL and 0.12 pg each. Furthermore, a remarkable adverse effect (p < 0.05) was observed on children's school performances as a result of increased BPbs. As BPbs increased by 10 µg/L, children's scores for Chinese, Math and English decreased by 0.42 points, 0.39 points and 0.87 points, respectively. In summary, our study indicated that lead exposure can have adverse health effects on children's erythrocyte parameters, BMI, and school performances.

Indium oxide nanoparticles induce lung intercellular toxicity between bronchial epithelial cells and macrophages.

Concerns have been raised over the safety and health of industrial workers exposed to indium oxide nanoparticles (IO-NPs) when working. IO-NPs were previously shown in vitro and in vivo to be cytotoxic, but the mechanism of pathogenesis was unclear. In this study, the effects of IO-NPs on lung cells associated with respiratory and immune barriers and the toxic effects of intercellular cascades were studied. Here IO-NPs had acute toxicity to Wistar rats over a time course (5 days post-intratracheal instillation). Following treatment epithelial cells (16HBE) or macrophages (RAW264.7) with IO-NPs or IO fine particles (IO-FPs), the damage of 16HBE cells caused by IO-NPs was serious, mainly in the mitochondrial and rough endoplasmic reticulum. The lactate dehydrogenase level also showed that cytotoxicity in vitro was more serious for IO-NPs compared with IO-FPs. The level of In3+ (examined by inductively coupled plasma mass spectrometry) in 16HBE cells was 10 times higher than that in RAW cells. In3+ , releasing from IO-NPs absorbed by 16HBE cells, could not only significantly inhibit the phagocytosis and migration of macrophages (P < .0001), but also stimulate RAW cells to secrete high levels of inflammatory cytokines. IO-NPs can directly damage pulmonary epithelial cells. The In3+ released by epithelial cells affect the phagocytosis and migration of macrophages, which may be a new point for the decrease in the clearance of alveolar surfactants and the development of IO-related pulmonary alveolar proteinosis.

Toxicological Evaluation of Graphene-Family Nanomaterials.

With the extending applications, graphene-family nanomaterials begin to enter people's life via various ways, largely increasing the exposure frequencies. In spite of the increasing toxicological studies, the biosafety of graphene-based nanomaterials still remains elusive. Graphene oxide (GO), an oxidation derivative of graphene, is considered as one of the recently-emerging nanomaterials attractive for biomedical applications. Accompanied with the prospect of applications are the great concerns about its biosafety for human and environment. Herein, this review intends to systematically summarize the research on GO toxicity both in vitro and in vivo followed by deep discussions about the toxicological mechanisms. The currently reported toxicity of GO mainly includes inhalation toxicity, ingestion toxicity, dermal toxicity and hemocompatibility depending on exposure routes. The toxicity evaluation of GO using non-rodent organisms (zebrafish, Caenorhabditis elegans and drosophila, etc.) is also summarized, supplementary to in vivo toxicity of GO. Based on the comprehensive summary of the reported GO-induced toxicity, our review suggests considerable emphasis being put on the balance of benefits and risks when employing the nanotechnology.

Organs Distribution and Injury After Repeated Intratracheal Instillations of Nano-In2O3 Particles into the Lungs of Wistar Rats.

Elevated industrial production and broaden applications of indium oxide materials have increased concerns over the occupational exposure of industry workers. Respirable In2O3 particles have been identified in the workplaces and lung of indium-processing workers. The aim of this study was to assess the indium distribution in vivo and organs injury induced by nano-In2O3 particles. More than 50% of nano-In2O3 particles were accumulated in the lungs after 8-week exposure period and caused serious pulmonary alveolar proteinosis (PAP) and pneumonia. The migration of nano-In2O3 particles from lungs to the other organs was very low and dose not steadily increase the indium burden in those organs except kidney and liver. The repeated intratracheal instillations of nano-In2O3 particles into the lungs of Wistar rats were dose-dependent increased the concentrations of serum indium.

The pharmaceutical multi-activity of metallofullerenol invigorates cancer therapy.

Currently, cancer continues to afflict humanity. The direct destruction and killing of tumor cells by surgery, radiation and chemotherapy gives rise to many side effects and compromised efficacy. Encouragingly, the rapid development of nanotechnology offers attractive opportunities to revolutionize the current situation of cancer therapy. Metallofullerenol Gd@C82(OH)22, in contrast to chemotherapeutics that directly kill tumor cells, demonstrates anti-tumor behavior with high efficiency and low toxicity by modulating the tumor microenvironment. Furthermore, Gd@C82(OH)22 has been recently reported to specifically target cancer stem cells. In this review, we give a concise introduction to the development of the fullerene family and then report the anti-tumor activity of Gd@C82(OH)22 based on its unique physicochemical characteristics, followed by a comprehensive summary of the anti-tumor biological mechanisms which target different components of the tumor microenvironment as well as the biodistribution and toxicity of Gd@C82(OH)22. Finally, we describe Gd@C82(OH)22 as a "particulate medicine" to highlight its distinctions from conventional "molecular medicine", with considerable emphasis on the advantages of nanomedicine. The in-depth investigation of Gd@C82(OH)22 undoubtedly provides a constructive reference for the development of other nanomedicines, especially in the fullerene family. The application of nanotechnology in the medical field definitely provides a promising and favorable future for improving the current status of cancer therapy.

A Novel Drug Design Strategy: An Inspiration from Encaging Tumor by Metallofullerenol Gd@C82(OH)22.

Cancer remains a major threat to human health worldwide. Cytotoxicity has imposed restrictions on the conventional cytotoxic drug-based chemotherapy. The rapidly-developing nanomedicine has shown great promise in revolutionizing chemotherapy with improved efficiency and reduced toxicity. Gd@C82(OH)22, a novel endohedral metallofullerenol, was first reported by our research group to suppress tumor growth and metastasis efficiently without obvious toxicity. Gd@C82(OH)22 imprisons tumors by facilitating the formation of surrounding fibrous layers which is different from chemotherapeutics that poison tumor cells. In this review, the authors first reported the antineoplastic activity of metallofullerenol Gd@C82(OH)22 followed by further discussions on its new anti-cancer molecular mechanism-tumor encaging. On this basis, the unparalleled advantages of nanomedicine in the future drug design are discussed. The unique interaction modes of Gd@C82(OH)22 with specific targeted biomolecules may shed light on a new avenue for drug design. Depending on the surface characteristics of target biomolecules, nanomedicine, just like a transformable and dynamic key, can self-assemble into suitable shapes to match several locks for the thermodynamic stability, suggesting the target-tailoring ability of nanomedicine.

The Pneumotoxic Effect and Indium Ion Release Induced by Indium Tin Oxide Nanoparticles.

With the increasing industrial production and the broaden applications of indium tin oxide (ITO) materials, frequent exposure has posed great concerns for people, especially the workers in the indium related manufacturing plants. The exposed-workers have been reported to adverse effect and even die from the ITO-induced pulmonary disorders called "indium lung." In addition to the epidemiologic studies, the increasing animal studies also demonstrated the lung injuries induced by the acute or chronic respiratory exposure of ITO nanoparticles (ITO NPs). They could enter into the cells owing to the small particle size and induce oxidative stress, inflammatory responses, cytotoxicity or even genotoxicity. The indium ions released from the ITO particles via lysosomal acidification considered as the actual entity responsible for the toxicity of ITO NPs. To date, no effective therapies are available against ITO-induced pulmonary diseases, which calls for the full explorations of the pathological factors. Our present mini-review summarizes the current reports on ITO nanoparticles-induced pneumotoxic effect with focus on the indium ion release, which could help warrant the health risks of ITO and other ITO-based materials.