Main Organs Research Articles

BMSCs-driven graphite oxide-grafted-carbon fibers reinforced polyetheretherketone composites as functional implants: in vivo biosafety and osteogenesis

Mesenchymal stem cells (MSCs) are increasingly becoming a potential treatment approach for bone injuries due to the multi-lineage differentiation potential, ability to recognize damaged tissue sites and secrete bioactive factors that can enhance tissue repair. The aim of this work was to improve osteogenesis of carbon fibers reinforced polyetheretherketone (CF/PEEK) implants through bone marrow mesenchymal stem cells (BMSCs)-based therapy. Moreover, bioactive graphene oxide (GO) was introduced into CF/PEEK by grafting GO onto CF to boost the osteogenic efficiency of BMSCs. Subsequently, CF/PEEK was implanted into the symmetrical skull defect models of SD rats. Then in vivo biosafety and osteogenesis were evaluated. The results indicated that surface wettability of CF/PEEK was effectively improved by GO, which was beneficial for the adhesion of BMSCs. The pathological tissue sections stained with H&E showed no significant pathological change in the main organs including heart, liver, spleen, lung and kidney, which indicated no acute systemic toxicity. Furthermore, bone mineralization deposition rate of CF/PEEK containing GO was 2.2 times that of pure CF/PEEK. The X-ray test showed that the surface of CF/PEEK containing GO was obviously covered by more newly formed bone tissue than pure CF/PEEK after 8 weeks of implantation. This work demonstrated that GO effectively enhanced surface bioactivity of CF/PEEK and assisted BMSCs in accelerating differentiation into bone tissue, providing a feasible strategy for improving osteogenesis of PEEK and CF/PEEK.

Seedlings of Poncirus trifoliata exhibit tissue-specific detoxification in response to NH4 + toxicity.

Ammonium nitrogen (NH4 +-N) is essential for fruit tree growth, but the impact of excess NH4 +-N from fertilizer on evergreen citrus trees is unclear. In a climate chamber, 8-month-old citrus plants were exposed to five different hydroponic NH4 +-N concentrations (0, 5, 10, 15 and 20 mm) for 1 month to study effects of NH4 +-N on growth characteristics, N uptake, metabolism, antioxidant enzymes and osmotic regulatory substances. Application of 10 mm NH4 +-N adversely affected root plasma membrane integrity, root physiological functions, and plant biomass. MDA, CAT, POD, APX and SOD content were significantly correlated with leaf N metabolic enzyme activity (GOGAT, GDH, GS and NR). GDH was the primary enzyme involved in NH4 +-N assimilation in leaves, while the primary pathway involved in roots was GS-GOGAT. Under comparatively high NH4 + addition, roots were the main organs involved in NH4 + utilization in citrus seedlings. Our results demonstrated that variations in NH4 + concentration and enzyme activity in various organs are associated with more effective N metabolism in roots than in leaves to prevent NH4 + toxicity in evergreen woody citrus plants. These results provide insight into the N forms used by citrus plants that are important for N fertilizer management.

Methods of radiology in the diagnostics of chronic liver diseases

Background. Chronic liver disease is one of the most common diseases. In many countries, liver disease is among the top five causes of death. The liver is one of the main organs responsible for basic metabolic functions, protein and hormone synthesis, detoxification and waste elimination. In chronic liver disease, there is a continuous process of inflammation, destruction and regeneration, ultimately leading to severe dysfunction, causing the development of fibrosis and cirrhosis. The main task of the radiation diagnosis of chronic liver disease is the development and introduction into clinical practice of new noninvasive biomarkers for a comprehensive assessment of the structure of the liver parenchyma in order to choose further treatment tactics.Aim a comprehensive analysis of the modern possibilities of radiation imaging methods in the diagnosis of chronic liver disease.Materials and methods. The analysis of 107 modern publications of domestic and foreign literature devoted to the diagnosis of chronic liver disease of various etiologies was carried out.Conclusion. the review reflects the most common modern and promising methods of radiodiagnosis for chronic liver disease, which in most cases make it possible to avoid invasive interventions in the process of establishing a diagnosis and monitoring the response to treatment

Integrated metabolome and transcriptome analyses reveal the molecular mechanism underlying dynamic metabolic processes during taproot development of Panax notoginseng

BackgroundPanax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown.ResultsWe carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis.ConclusionsThese results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.

Atmospheric fine particulate matter (PM2.5) induces pulmonary fibrosis by regulating different cell fates via autophagy

The presence of respiratory diseases demonstrates a positive correlation with atmospheric fine particulate matter (PM2.5) exposure. The respiratory system is the main target organ affected by PM2.5, and exposure to PM2.5 elevates the likelihood of developing pulmonary fibrosis (PF). In this study, lung epithelial cell (BEAS-2B) and fibroblast (NIH-3T3) were used as in vitro exposure models to explore the mechanisms of PF. PM2.5 exposure caused mitochondrial damage in BEAS-2B cells and increased a fibrotic phenotype in NIH-3T3 cells. Epithelial cells and fibroblasts have different fates after PM2.5 exposure due to their different sensitivities to trigger autophagy. Exposure to PM2.5 inhibits mitophagy in BEAS-2B cells, which hinders the removal of damaged mitochondria and triggers cell death. In this process, the nuclear retention of the mitophagy-related protein Parkin prevents it from being recruited to mitochondria, resulting in mitophagy inhibition. In contrast, fibroblasts exhibit increased levels of autophagy, which may isolate PM2.5 and cause abnormal fibroblast proliferation and migration. Fibrotic phenotypes such as collagen deposition and increased α-actin also appear in fibroblasts. Our results identify PM2.5 as a trigger of PF and delineate the molecular mechanism of autophagy in PM2.5 induced PF, which provides new insights into the pulmonary injury.

Chenopodium Ambrosioides Linn Mitigates Bone Loss in Rats with Periodontitis.

Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis. This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats. For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract. Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts (p< 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found. In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent.

Sensory neurobiology: Muscles power pheromone sensation

While we understand how the five main sensory organs enable and facilitate stimulus detection, little is known about how the vomeronasal organ enables pheromone sensation. A new study finds specialized muscles poised to coordinate stimulus delivery, dynamics, and arousal.

Discovery of 2,9-diaryl-6-carbamoylpurines as a novel class of antitubercular agents

A series of novel 9-alkyl/aryl-2-aryl-6-carbamoylpurines were synthesized, and their activity against Mycobacterium tuberculosis strain H37Rv was assessed. The SAR analysis on the first set of derivatives, with an alkyl or aryl unit at N-9 and a phenolic unit at C-2, showed that the activity depends on the purine ring substituents at N-9 and C-2. A phenyl group at N-9 combined with a 3-hydroxyphenyl or 4-hydroxyphenyl at C-2 improve the activity. The most active compound of this set has a phenyl group at N-9 and a 4-hydroxyphenyl group at C-2, displaying an IC90 = 1.2 μg/mL and a selectivity index higher than 25.5. This compound served as a Hit to design the second set of derivatives. A phenyl group at N-9 was maintained, and the group at C-2 was diversified. The SAR analysis showed that the aryl unit at C-2 must have an oxygen or nitrogen atom bonded in the para position. A proton, a small alkyl or a substituted aryl group may also be bonded to the oxygen. The compound with the 4-methoxyphenyl group at C-2, 1Bd, exhibits the highest activity with an IC90 < 0.19 μg/mL. This compound is highly potent against M. tuberculosis strain H37Rv and non-toxic for VERO mammalian cells with an SI > 153.8. Compound 1Bd was also non-cytotoxic against primary macrophage cultures at IC90, 2xIC90, and 10xIC90 and significantly reduced the bacterial load in M. tuberculosis-infected macrophages at the same concentrations. Compound 1Bd showed a favorable pharmacokinetic profile when administered orally, with major lung and liver accumulation. In vivo antimycobacterial efficacy of 1Bd was tested at 25 mg/kg. At the tested regimen, a decrease in bacterial burden was observed in the liver. Optimization of the treatment regimen should be performed to fully potentiate the in vivo efficacy of our lead molecule, particularly in the lung, the main target organ of M. tuberculosis.

Fine root production, mortality, and turnover in response to simulated nitrogen deposition in the subtropical Abies georgei (Orr) forest

Increased nitrogen deposition has important effects on below-ground ecological processes. Fine roots are the most active part of the root system in terms of physiological activity and the main organs for nutrient and water uptake by plants. However, there is still a limited understanding of how nitrogen deposition affects the fine root dynamics in subtropical Abies georgei (Orr) forests. Consequently, a three-year field experiment was conducted to quantify the effects of three forms of nitrogen sources ((NH4)2SO4, NaNO3, and NH4NO3) at four levels (0, 5, 15, and 30 kg N·ha−1·yr−1) on the fine root dynamics in Abies georgei forests using a randomized block-group experimental design and minirhizotron technique. The first year of nitrogen addition did not affect the first-class fine roots (FR1, 0 < diameter < 0.5 mm) and second-class fine roots (FR2, 0.5 < diameter < 1.0 mm). The next two years of nitrogen addition significantly increased the production, mortality, and turnover of FR1 and FR2; the three year of nitrogen addition did not affect the dynamics of the third- class fine roots (FR3, 1.0 < diameter < 1.5 mm) and fourth- class fine roots (FR4,1.5 < diameter < 2.0 mm). Nitrogen addition positively affected the dynamics of FR1, FR2, FR3 and FR4 by positively affecting the carbon, nitrogen, and phosphorus contents of fine roots and indirectly affecting the soil pH. Increased carbon allocation to FR1 and FR2 may represent a phosphorus acquisition strategy when nitrogen is not the limiting factor. The nitrogen addition forms and levels affected the fine root dynamics in the following orde: NH4NO3 > (NH4)2SO4 > NaNO3 and high nitrogen > medium nitrogen > low nitrogen. The results suggest that the different-diameter fine root dynamics respond differently to different nitrogen addition forms and levels, and linking the different-diameter fine roots to nitrogen deposition is crucial.

The size-dependence and reversibility of polystyrene nanoplastics-induced lipid accumulation in mice: Possible roles of lysosomes

Nanoplastics (NPs) continue to accumulate in global aquatic and terrestrial systems, posing a potential threat to human health through the food chain and/or other pathways. Both in vivo and in vitro studies have confirmed that the liver is one of the main organs targeted for the accumulation of NPs in living organisms. However, whether exposure to NPs induces size-dependent disorders of liver lipid metabolism remains controversial, and the reversibility of NPs-induced hepatotoxicity is largely unknown. In this study, the effects of long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs) on lipid accumulation were investigated in terms of autophagy and lysosomal mechanisms. The findings indicated that hepatic lipid accumulation was more pronounced in mice exposed to 100 nm PS-NPs compared to 500 nm PS-NPs. This effect was effectively alleviated after 50 days of self-recovery for 100 nm and 500 nm PS-NPs exposure. Mechanistically, although PS-NPs exposure activated autophagosome formation through ERK (mitogen-activated protein kinase 1)/mTOR (mechanistic target of rapamycin kinase) signaling pathway, the inhibition of Rab7 (RAB7, member RAS oncogene family), CTSB (cathepsin B), and CTSD (cathepsin D) expression impaired lysosomal function, thereby blocking autophagic flux and contributing to hepatic lipid accumulation. After termination of PS-NPs exposure, lysosomal exocytosis was responsible for the clearance of PS-NPs accumulated in lysosomes. Furthermore, impaired lysosomal function and autophagic flux inhibition were effectively alleviated. This might be the main reason for the alleviation of PS-NPs-induced lipid accumulation after recovery. Collectively, we demonstrate for the first time that lysosomes play a dual role in the persistence and reversibility of hepatotoxicity induced by environmental relevant doses of NPs, which provide novel evidence for the prevention and intervention of liver injury associated with nanoplastics exposure.

α1-Antitrypsin deficiency

α1-Antitrypsin deficiency is classified as an orphan disease. The main target organs are the lungs, liver and skin. Typical respiratory manifestations are emphysema and bronchiectasis, which often lead to disability as the disease progresses. To slow the progression of lung pathology, replacement therapy with an α1-proteinase inhibitor is used worldwide.The aim of this article is to familiarize physicians with a rare lung disease that leads to the early development of emphysema and chronic obstructive pulmonary disease.Conclusion. Early detection of lung pathology associated with α1-antitrypsin deficiency allows timely prescription of the necessary replacement therapy, which in turn leads to an increase in the duration and improvement in the quality of life of patients with this pathology.

Gene editing: a near future for the treatment of genetic kidney diseases

The study by Chen etal. is the first to apply the revolutionary genetic engineering tool, base editing, in a rat model for the treatment of primary hyperoxaluria type 1, a disease that originates in the liver but in which the kidney is the main organ affected. This commentary contextualizes and describes the gene-editing technology applied by the authors, provides an interpretation and opinion of their results, and indicates possible future applications.

A Review on Psychotria calceata E.M.A. Petit and its Botanical Characteristics and Traditional Uses

Abstract: The genus Psychotria, comprising approximately 1,834 species globally, represents the largest genus within the Rubiaceae family. A substantial number of these species are indigenous to West and Central Africa, notably Cameroon, where comprehensive scientific investigations are, however, notably lacking. Yet, the therapeutic and dietary applications of these species are likely to find a potential justification of their pharmacological attributes, as attested by some studies. It goes without saying that a comprehensive review on the utilization of Psychotria calceata E.M.A. Petit in traditional medicine vis-à-vis its pharmacological properties remains an unexplored territory, and is needed to be investigated. The primary objective of this investigation was to compile data pertaining to the botanical characteristics, phytochemical composition, toxicity and traditional uses of Psychotria calceata. This endeavor aimed to establish a rigorous scientific database and identify areas warranting further research. Relevant information on Psychotria calceata, spanning from 1964 to August 2022, was systematically collected from various scientific databases, encompassing Scopus, Research Gate, SCIENCEDOMAIN, Google Scholar, PubMed, Research4Life (Hinari), Web of Science, Science Direct, Current Content Connect, Springer Link, Global Plants, Cochrane Library, and Scirus. Validation of scientific nomenclature was conducted using The World Flora Online. Eight families of secondary metabolites were identified in the aqueous extract of Psychotria calceata leaves. These families included alkaloids, phenolic compounds, flavonoids, tannins, glycosides, coumarins, anthocyanins, and saponins. In addition, in vivo toxicological studies of these same extracts indicated a lethal dose 50 (LD50) of over 5.000 mg/kg body weight, allowing the classification of Psychotria calceata as non-toxic. Histological examination of sections of the main purifying organs, the kidneys, liver, and spleen, corroborated this result, revealing the absence of structural abnormalities within these organs. Psychotria calceata has emerged as a repository of diverse chemical compounds endowed with a range of pharmacological activities. It also holds a prominent position in traditional medicine and dietary practices. However, the nexus between these chemical constituents and the pharmacodynamics of Psychotria calceata remains unestablished due to the paucity of experimental investigations. Consequently, further studies on Psychotria calceata are imperative, with the aspiration of unlocking scientific discoveries and advancing our understanding in this domain

PROBLEMS OF UN SECURITY COUNCIL REFORM AND ITS LEGITIMACY

This article discusses the role of the United Nations Security Council in international security law and the need to reform the Security Council as the main organ charged with the maintenance of international peace and security. The author deeply analyzes main issues of reform of the Council and proposals of states in this regard. In particular, formats of cooperation on reforming the Security Council, such as the Big Four, the Consensus Group, the Annan Plan, and the African Group will be more widely covered. In the article, the author develops several proposals for the effective organization of the Council's activities.

The Effects of Second-hand Smoke on Liver Cancer

Secondhand tobacco smoke contains at least 69 carcinogens, such as nitrosamines, hydrocarbons, tar, and vinyl chloride. The liver is the main metabolic organ for these products. When the human body is exposed to these carcinogens for a long time, the carcinogens will cause "mutations" in the genes in the body and gradually accumulate, causing the cells to be unable to "function" normally, eventually leading to the occurrence of malignant tumors.Harmful substances such as nicotine in tobacco can activate cytokines and intermediate products of fiber formation, which accelerate the process of liver fibrosis and hinder the recovery of liver function in patients with liver disease. The condition will worsen with the increase in daily smoking, promoting the occurrence of liver cancer.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

Transcriptional profile of human thymus reveals IGFBP5 is correlated with age-related thymic involution.

Thymus is the main immune organ which is responsible for the production of self-tolerant and functional T cells, but it shrinks rapidly with age after birth. Although studies have researched thymus development and involution in mouse, the critical regulators that arise with age in human thymus remain unclear. We collected public human single-cell transcriptomic sequencing (scRNA-seq) datasets containing 350,678 cells from 36 samples, integrated them as a cell atlas of human thymus. Clinical samples were collected and experiments were performed for validation. We found early thymocyte-specific signaling and regulons which played roles in thymocyte migration, proliferation, apoptosis and differentiation. Nevertheless, signaling patterns including number, strength and path completely changed during aging, Transcription factors (FOXC1, MXI1, KLF9, NFIL3) and their target gene, IGFBP5, were resolved and up-regulated in aging thymus and involved in promoting epithelial-mesenchymal transition (EMT), responding to steroid and adipogenesis process of thymic epithelial cell (TECs). Furthermore, we validated that IGFBP5 protein increased at TECs and Hassall's corpuscle in both human and mouse aging thymus and knockdown of IGFBP5 significantly increased the expression of proliferation-related genes in thymocytes. Collectively, we systematically explored cell-cell communications and regulons of early thymocytes as well as age-related differences in human thymus by using both bioinformatic and experimental verification, indicating IGFBP5 as a functional marker of thymic involution and providing new insights into the mechanisms of thymus involution.

Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose-stimulated insulin secretion.

Postprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated. LPLAT10 expression is low in the liver, the main organ that regulates metabolism, under normal conditions. Here, we investigated whether overexpression of LPLAT10 in the liver leads to improved glucose metabolism. For overexpression, we generated an LPLAT10-expressing adenovirus (Ad) vector (Ad-LPLAT10) using an improved Ad vector. Postprandial hyperglycemia was suppressed by the induction of glucose-stimulated insulin secretion in Ad-LPLAT10-treated mice compared with that in control Ad vector-treated mice. Hepatic and serum levels of phosphatidylcholine 40:7, containing C18:1 and C22:6, were increased in Ad-LPLAT10-treated mice. Serum from Ad-LPLAT10-treated mice showed increased glucose-stimulated insulin secretion in mouse insulinoma MIN6 cells. These results indicate that changes in hepatic phosphatidylcholine species due to liver-specific LPLAT10 overexpression affect the pancreas and increase glucose-stimulated insulin secretion. Our findings highlight LPLAT10 as a potential novel therapeutic target for T2DM.

A DNA nanostructure-Hif-1α inducer complex as novel nanotherapy against cisplatin-induced acute kidney injury.

Since its discovery in 1978, cisplatin-based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin-induced acute kidney injury (AKI), which occurs in 30% of cisplatin-treated patients. Unfortunately, no effective solution for preventing or managing this severe complication, which greatly impacts its clinical administration. Kidney is the main organ injured by cisplatin, and the injury is related to cisplatin-induced cell apoptosis and DNA injury. Therefore, to achieve the safe use of cisplatin in tumour treatment, the key lies in identifying a kidney treatment that can effectively minimize cisplatin nephrotoxicity. Here, we successfully synthesized and applied a DNA-nanostructure complex, named TFG, which contains tetrahedral framework nucleic acids (tFNAs) and FG-4592, a novel Hif-1α inducer. As cargo, TFG is composed entirely of DNA strands. It possesses low nephrotoxicity and renal aggregation properties while FG-4592 is able to relieve renal injury by downregulating the apoptosis signal pathways. And it can relieve cisplatin-induced renal injury when taken cisplatin treatment. This work aims to enhance chemotherapy protection in tumour patients by using TFG, a DNA-based nanomedicines to kidney. This work has the potential to revolutionize the treatment of renal diseases, particularly drug-induced kidney injury, leading to improved clinical outcomes.

Toxicokinetic study of scandium oxide in rats

Canada has recently invested in the large-scale exploitation of scandium oxide. However, there are no studies available to date to understand its toxicokinetics in the animal or human body, which is necessary to assess exposure and health risks. The aim of this research was to investigate the toxicokinetics of absorbed scandium oxide (Sc2O3) using the rat as an experimental model. Male Sprague-Dawley rats were injected intravenously with 0.3 or 1 mg Sc2O3/kg body weight (bw). Blood and excreta (urine and feces) were collected sequentially during a 21-day period, and main organs (liver, spleen, lungs, kidneys, brain) were withdrawn at sacrifice on day 21. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for the measurement of Sc element in the different samples. The mean residence time (MRTIV) calculated from the blood profile was 19.7 ± 5.9 h and 43.4 ± 24.6 h at the lower and higher doses, respectively. Highest tissue levels of Sc were found in the lungs and liver; respective lung values of 10.6 ± 6.2% and 3.4 ± 2.3% of the Sc dose were observed at the time of sacrifice while liver levels represented 8.9 ± 6.4% and 4.6 ± 1.1%. Elimination of Sc from the body was not complete after 21 days. Cumulative fecal excretion over the 21-day collection period represented 12.3 ± 1.3% and 5.9 ± 1.0% of the lower and higher Sc doses, respectively, and showed a significant effect of the dose on the excretion; only a small fraction of the Sc dose was recovered in urine (0.025 ± 0.016% and 0.011 ± 0.004% in total, respectively). In addition to an effect of the dose on the toxicokinetics, results highlight the importance of the lung as a site of accumulation and retention of Sc2O3, which raises the question of the risks of effects related to respiratory exposure in workers. The results also question the relevance of urine as a matrix for biological exposure monitoring. A more in-depth inhalation toxicokinetic study would be necessary.