Carcinogenic Agents Research Articles

Hemangiossarcoma hepático em cadela da raça Dobermann

In this work, a case is reported of a young Doberman dog, with a history of ingesting cica palm (Cycas revoluta), in the first months of life, she presented changes in liver enzymes. The patient was diagnosed with primary hepatic hemangiosarcoma, which is a malignant neoplasm of epithelial cells, and is highly metastatic in its visceral form. The diagnosis was made through exploratory laparotomy and histopathological results. In addition, complementary hematological and imaging tests were performed for follow-up. Eight chemotherapy sessions with doxorubicin were performed. Due to the aggressiveness of this neoplasm, the prognosis is reserved to unfavorable. During treatment, the patient developed dilated cardiomyopathy, progressing to heart failure, which was the cause of death. The objective of this report is to present a case of primary hepatic hemangiosarcoma, raising the possible cause related to the carcinogenic agent responsible for its development.

Aristolochia clematitis L. Ethanolic Extracts: In Vitro Evaluation of Antioxidant Activity and Cytotoxicity on Caco-2 Cell Line.

Aristolochia sp. plants are used in traditional medicine because of their immunostimulatory and anticarcinogenic properties, despite their content of aristolochic acids (AAs), carcinogenic and nephrotoxic agents. Therefore, ethanolic extracts of Aristolochia clematitis leaves, a specie growing in Western Romania, were obtained to study antioxidant and cytotoxic effects. The antioxidant capacity of the extract was evaluated by five in vitro chemical-based assays, proving that ABTS assay was a better method for this type of evaluation showing an IC50 of 160.89 ± 0.21 µg/mL. Furthermore, the cytotoxic effects of the extract were established by an IC50 of 216 µg/mL for 24 h by MTT assay, followed by a cell-based assay on Caco-2 cells by the ABTS method. The antioxidant effects of the A. clematitis extract demonstrate potential therapeutic applications in complementary medicine.

Comparison of the cytotoxic impact of samsum ant venom (Brachyponera sennaarensis) administration routes on quantitative histological analysis of thymus

Samsum (Brachyponera sennaarensis) ant venom contains several peptides that have an aggressive impact on the architecture of the internal organs including the thymus. The objective of this study was to evaluate the effectiveness of venom with various doses as a toxin insult by examining the histological alterations and measurable biochemical parameters in the thymus. Forty Wistar albino rats separated into seven groups were used.Data demonstrated statistically significant hyperplasia in the cellular density, shrinkage in cortical thickness, and medullary area in the venom- intraperitoneally treated group compared to the − orally treated group. Additionally, there was a prominent increase in apoptotic cells TGB, the density of lesions, and hemorrhagic cysts effects of the venom on thymic cells. There was a notable higher intensity of pathological features in the thymus.Results validated the role of SAV in the general thymic atrophy in the histological structure of thymus tissues and acted as a carcinogenic agent. The structural analysis of the thymus revealed that a larger dosage of SAV produced a thymoma in the histoarchitecture. The differences between the low dose of SAV-treated groups orally and (IP) were not statistically significant in some analyses. In terms of the thymus tissue’s structure, the administration of a high dose of (450 µl) intraperitoneally had the worst impact on the health of the thymus.

Modeling of hexavalent chromium removal onto natural zeolite from air stream in a fixed bed column

The increasing use of hexavalent chromium (Cr(VI)) has exposed large populations to this environmental and occupational carcinogenic agent. Therefore, researchers have been interested in removing this substance through adsorbents. This study aimed to investigate the efficiency of natural zeolite in the direct adsorption of Cr(VI) from airflow and its adsorption modeling. In this study, a nebulizer device produced the Cr(VI) mist. The efficiency of natural zeolite in Cr(VI) adsorption from airflow, modeling of fixed column adsorption, and the effective parameters on adsorption efficiency including the initial concentration of chromium, airflow rate, and adsorption bed depth were studied. To facilitate the prediction of the performance of natural zeolite’s adsorption column, Yoon–Nelson, Thomas, BDST, and Buhart–Adams models were used. The results showed that the adsorption capacity diminished with increased airflow rate and initial concentration, while it increased with elevated height of the adsorption bed. Yoon–Nelson, Thomas, and BDST models corresponded to experimental data with a correlation coefficient of 0.9933, but the information of the Buhart–Adams model had a lower correlation coefficient (around 0.6677). In conclusion, natural zeolite can be used as an efficient low-cost adsorbent for directly Cr(VI) removing from the airflow in a fixed bed column.

3D/2D-Bismuth Oxybromide Spheres with Selenium-Doped Graphitic Carbon Nitride Sheets: An Efficient Electrocatalyst for the Detection of Arsenic Drug Roxarsone.

Heavy metals are crucial carcinogenic agents threatening the environment and living habituates. Among them, arsenic (As) is an important metalloid that is categorized as a group I toxic carcinogen. Roxarsone (RX) is an organoarsenic antibiotic compound primarily used as a veterinarian drug and growth promoter for poultry animals. The extensive usage of RX increased the accumulation of As in living beings and the ecosystem. Therefore, we have prepared an electrochemical sensor based on 3D bismuth oxybromide with 2D selenium-doped graphitic carbon nitride (BOB/SCN) electrocatalyst for the rapid detection of RX. The elemental and structural details were thoroughly investigated with several spectroscopic techniques. The electrochemical properties were measured by impedance and voltammetric measurements. The electrocatalytic behavior toward the RX was estimated with different voltammetric methods. Therefore, our BOB/SCN-based electrochemical sensor demonstrated a low detection limit (2.3 nM), low quantification value (7.7 nM), optimal sensitivity (0.675 μA μM-1 cm-2), and good linear ranges (0.01-77 and 77-857 μM). Additionally, this sensor showed good electrochemical performance and was applied to monitor the RX in various real samples with remarkable recoveries. Based on these results, our BOB/SCN sensor is a promising electrochemical platform for determining RX.

Facile scalable one-flow synthesis of ionizable cationic lipid library as precursors of nanoparticle carriers

A variety of ionizable and cationic lipids have been synthesized as precursors for nanoparticle carriers. However, the laborious synthetic routes in batch reactors often involve the use of toxic and carcinogenic agents, as well as challenge of removing gaseous byproducts. In this study, we present facile one-flow micro-reaction process that enables the synthesis of 11 ionizable lipids as well as 7 cationic lipids, including the well-known DODAP and DOTAP. These lipids can be scaled up to produce approximately ∼10g/h by using a straightforward size-up approach. The development of the lipid library was involved generating highly moisture-sensitive acyl chloride at 25 °C for 1.5 min. The toxic byproducts such as HCl, CO2 and CO were subsequently removed using a liquid–gas separator. The esterification with dimethylamino-1,2-diol at 25 °C for 3 min, monitored in-line with FTIR, completed the process. Additionally, the synthesized ionizable lipids were converted to cationic lipids with methyl sulfate, chloride ions via dimethyl sulfate and Steglich esterification in a continuous flow system. Finally, the produced DODAP was transformed into a uniform-sized LNPs (64 nm, PDI 0.07) and liposomal nanoparticles (72 nm, PDI 0.05) while DOTAP was converted to liposomes (55 nm, PDI 0.08) using a custom micro-mixer. This efficient platform for lipid synthesis significantly contributes to the practical applications of lipid-based nanomedicines.

Fast-track adaptive laboratory evolution of Cupriavidus necator H16 with divalent metal cations.

Microbial strain improvement through adaptive laboratory evolution (ALE) has been a key strategy in biotechnology for enhancing desired phenotypic traits. In this Biotech Method paper, we present an accelerated ALE (aALE) workflow and its successful implementation in evolving Cupriavidus necator H16 for enhanced tolerance toward elevated glycerol concentrations. The method involves the deliberate induction of genetic diversity through controlled exposure to divalent metal cations, enabling the rapid identification of improved variants. Through this approach, we observed the emergence of robust variants capable of growing in high glycerol concentration environments, demonstrating the efficacy of our aALE workflow. When cultivated in 10% v/v glycerol, the adapted variant Mn-C2-B11, selected through aALE, achieved a final OD600 value of 56.0 and a dry cell weight of 15.2gL-1, compared to the wild type (WT) strain's final OD600 of 39.1 and dry cell weight of 8.4gL-1. At an even higher glycerol concentration of 15% v/v, Mn-C2-B11 reached a final OD600 of 48.9 and a dry cell weight of 12.7gL-1, in contrast to the WT strain's final OD600 of 9.0 and dry cell weight of 3.1gL-1. Higher glycerol consumption by Mn-C2-B11 was also confirmed by high-performance liquid chromatography (HPLC) analysis. This adapted variant consumed 34.5 times more glycerol compared to the WT strain at 10% v/v glycerol. Our method offers several advantages over other reported ALE approaches, including its independence from genetically modified strains, specialized genetic tools, and potentially carcinogenic DNA-modifying agents. By utilizing divalent metal cations as mutagens, we offer a safer, more efficient, and cost-effective alternative for expansion of genetic diversity. With its ability to foster rapid microbial evolution, aALE serves as a valuable addition to the ALE toolbox, holding significant promise for the advancement of microbial strain engineering and bioprocess optimization.

Mitigating Effect of Matricin Against Benzo(a)pyrene-induced Lung Carcinogenesis in Experimental Mice Model.

Lung cancer is a life-threatening disease that is still prevalent worldwide. This study aims to evaluate the effects of matricin, a sesquiterpene, on the carcinogenic agent benzo(a)pyrene [B(a)P]-induced lung cancer in Swiss albino mice. Lung cancer was induced by oral administration of B(a)P at 50 mg/kg b. wt. in model Swiss-albino mice (group II) as well in experimental group III, and treated with matricin (100 mg/kg b. wt.) in group III. Upon completion of treatment for 18 weeks, the changes in body weight, tumor formation, enzymatic and non-enzymatic antioxidant levels (GSH, SOD, GPx, GR, QR, CAT), lipid peroxidation (LPO) level, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), immunoglobulin levels (IgG, IgM), apoptosis markers (Bax, Bcl-xL), tumor markers (carcinoembryogenic antigen (CEA), neuron-specific enolase (NSE)), and histopathological (H&E) alterations were determined. The results indicate that B(a)P caused a significant increase of tumor formation in the lungs, increased tumor markers and inflammatory cytokines in serum, and depletion of enzymatic/ non-enzymatic antioxidants and immunoglobulins, compared to the untreated control group. Matricin treatment significantly reversed the changes caused by B(a)P as evidenced by the biochemical and histopathological assays. The changes caused by matricin clearly indicate the cancer-preventive effects of matricin against B(a)P-induced lung cancer in animal models, which can be attributed to the antioxidant activity, immunomodulation, and mitigation of the NF-kβ pathway.

A Scoping Review of Firefighters' Health Behaviors and Chronic Diseases

Objectives: Due to exposure to carcinogenic agents, firefighters are at increased risk for chronic diseases (e. g., cancer). It is unclear how much research has focused on firefighters' health behaviors that also could also contribute to firefighters' disease risk. In this scoping review, we aimed to (1) determine how much research has examined firefighters' health behaviors and (2) determine how many studies have assessed the association between health behaviors and chronic diseases. Methods: We searched electronic databases (e. g., PubMed/MEDLINE). We included studies if they measured at least one health behavior (diet, tobacco use, physical activity, sleep, alcohol consumption), regardless of assessing chronic diseases. We noted if the study included chronic diseases and if it examined an association between health behavior and chronic disease. Results: Overall, 126 articles were included that measured at least one health behavior. Physical activity and diet were the most studied health behaviors. About half of the studies included a chronic disease. Of those studies, 26 examined associations between the health behavior(s) and chronic diseases. Conclusions: There is a growing literature examining health behaviors among firefighters. This information can inform intervention development.

50 Hz magnetic field influences caspase-3 activity and cell cycle distribution in ionizing radiation exposed SH-SY5Y neuroblastoma cells

Purpose Earlier evidence suggests that extremely low frequency magnetic fields (ELF MFs) can modify the effects of carcinogenic agents. However, the studies conducted so far with ionizing radiation as the co-exposure agent are sparse and have provided inconclusive results. We investigated whether 50 Hz MFs alone, or in combination with ionizing radiation alter cell biological variables relevant to cancer and the biological effects of ionizing radiation. Materials and methods Human SH-SY5Y neuroblastoma cells were sham exposed or exposed to 100 or 500 µT MF for 24 h either before or after ionizing radiation exposure (0, 0.4 or 2 Gy). After the exposures, cells were assayed for viability, clonogenicity, reactive oxygen species, caspase-3 activity, and cell cycle distribution. Cell cycle distribution was assayed with propidium iodide staining followed by flow cytometry analysis and ROS levels were assayed together with cell viability by double staining with DeepRed and Sytox Blue followed by flow cytometry analysis. Results Increased caspase-3 activity was observed in cells exposed to 500 µT MF before or after ionizing radiation. Furthermore, exposure to the 500 µT MF after the ionizing radiation decreased the percentage of cells in S-phase. No changes in the ROS levels, clonogenicity, or viability of the cells were observed in the MF exposed groups compared to the corresponding sham exposed groups, and no MF effects were observed in cells exposed at 100 µT. Conclusions Only the 500 µT magnetic flux density affected SH-SY5Y cells significantly. The effects were small but may nevertheless help to understand how MFs modify the effects of ionizing radiation. The increase in caspase-3 activity may not reflect effects on apoptosis, as no changes were observed in the subG1 phase of the cell cycle. In contrast to some earlier findings, 50 Hz MF exposure after ionizing radiation was not less effective than MF treatment given prior to ionizing radiation.

Pre-mating exposure with hesperidin protects N-ethyl-N-nitrosourea-induced neurotoxicity and congenital abnormalities in next generation of mice as a model of glioma.

Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular membranes, proteins, chromosomes and genetic material. It is thought that compounds like hesperidin with high antioxidant and anticancer potential can reduce development of cancer induced by chemical carcinogens via neutralizing their oxidative damages. We investigated protective effect of hesperidin against N-Ethyl-N-Nitrosourea (ENU)-induced neurotoxicity, congenital abnormalities and possible brain cancer after exposure of mice during pregnancy as model of glioma. The mice were divided to four groups; control (normal saline), ENU (40mg/kg daily for three consecutive days from the 17th to the 19th of pregnancy), hesperidin (pretreated with 25mg/kg for 30 consecutive days, before mating) + ENU and hesperidin alone. Developmental toxicity parameters (the number of pregnant mice, stillbirths, abortion, live and dead offspring), behavioral tests (novel object recognition, open field and elevated plus maze) were performed. Moreover, the activity of butrylcholinesterase and acetylcholinesterase enzymes, oxidative markers and histopathological abnormalities were detected in brain tissue. Our data showed that conversely, the pretreatment of hesperidin reduces various degrees of developmental toxicity, neurobehavioral dysfunction, neurotoxicity, oxidative stress and histopathological abnormalities induced by ENU as a neurotoxic and carcinogenic agent in the next generation. In conclusion, pre-mating exposure with hesperidin may open new avenues for prevention of primary brain cancer in next generation and could be valuable for enhancing the antioxidant defense and minimizing the developmental and neurotoxicity of DNA alkylating agents.

Cancer risk in people living with HIV and solid organ transplant recipients: a systematic review and meta-analysis

Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I2=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I2=99·8%; 10·24 [8·48-12·35], I2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. US National Cancer Institute, National Institutes of Health.

Circulating tumor DNA (ctDNA) Detection via electrochemical Biosensing Tools

Cancer is characterized by the presence of mutated alleles in DNA, leading to the formation of tumors. A delayed diagnosis of this condition can result in fatal outcomes, making it a significant global cause of mortality. WHO has emphasized that early detection could significantly increase the chances of successful treatment and recovery. Traditional cancer diagnosis relies on invasive tissue biopsies, which pose risks to both patient’s and healthcare professionals due to the use of formaldehyde, a known carcinogenic agent, for specimen preservation. In recent times, liquid biopsies have emerged as a promising alternative, particularly for the analysis of circulating tumor DNA (ctDNA), a fraction of which originates from tumor cells and circulates in the bloodstream. However, conventional molecular genetic tests for ctDNA analysis are often costly and time-consuming. Advancements in technology and the field of nanoscience offer the potential to develop cost-effective, rapid, highly sensitive, and selective diagnostic tools. Among these, biosensors stand out as a promising option. In this article, we delve into the quantification of ctDNA in plasma, discuss amplification techniques for ctDNA, and explore the development of electrochemical-based biosensors tailored for ctDNA detection. Finally, we highlight recent studies and innovations in the field of ctDNA detection.

Neurotoxin-induced animal model of multiple sclerosis: Molecular mechanism focus

Background: Neurotoxins can alter the central nervous system. They induce severe clinical symptoms such as encephalopathy, convulsions, muscle paralysis, and respiratory failure. Hence, the neurotoxin can mimic human central nervous system disorders such as Multiple Sclerosis (MS) to study pathophysiology and drugs of development. Objective: This mini-review compared the neurotoxins for mimicking MS in animal models. Method: This study was a narrative review using the scientific electronic databases Scopus, PubMed, and Google Scholar. All related articles by keywords animal models, multiple sclerosis, and neurotoxins were collected by YP and BW. All authors contributed to manuscript development. Result: Cuprizone, ethidium bromide, lysolecithin, Myelin Oligodendrocyte Glycoprotein (MOG), and Myelin Essential Protein (MBP) are neurotoxins for MS animal models. Cuprizone is particularly relevant for use in studies addressing toxic mechanisms of the demyelination process and studies of therapeutic interventions. Ethidium bromide causes spinal cord demyelination with distinctive features in the oligodendrocytes and astrocytes. However, it is a carcinogen agent. Lysolecithin is suitable for old animal models because the duration for remyelination is relatively longer than others. MOG and MBP are preferable to resemble MS pathophysiology in humans. Conclusion: MOG and MBP are appropriate for generating animal multiple sclerosis models for further in vivo experiments.

Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.

4-methylimidazole can promote oxidative stress, inflammation and histopathological assessment following sub-chronic exposure in rats: mechanistic approaches

4-methylimidazole (4-MEI) as the main by-product of many foods like drink colas, beverages, soy sauce, meats, candy, vinegar and caramel color which is formed in a high temperature following millard reaction. Other data revealed that 4-MEI is a neurotoxic and carcinogenic agent in animals but the obscure mechanistic pathway on the liver of wistar rats after two month administration. Therefore, sub-chronic effects of 4-MEI (32 µg kg−1–64 mg kg−1) were conducted on the cytotoxicity and inflammatory biomarkers in the liver and then histopathological changes were evaluated following oral administration. Our data revealed that 4-MEI exposure enhanced protein and lipid oxidation, and decreased reduced glutathione and total antioxidant level (FRAP) with histopathological changes in rats in higher doses of 320 µg kg−1. Our data explored the potentially toxic role of 4-MEI on the liver via induction of oxidative stress, mitochondrial dysfunction with negative impacts on glutathione and Frap level, and a raise in protein carbonylation and lipid peroxidation in the different doses of 4-MEI which leads to cell death signaling in the liver. Increased nitric oxide (NO) levels suggested the involvement of inflammation in 4-MEI mechanistic toxicity. Our data explored the potential hepatotoxic of 4-MEI by considering its possible role in oxidative stress, inflammation, and mitochondrial dysfunction.

PCF Based Four-Channel SPR Biosensor With Wide Sensing Range.

In this article, we have demonstrated a highly sensitive four-channel photonic crystal fiber (PCF) based surface plasmon resonance (SPR) biosensor which can detect four different analytes simultaneously. To ease practical implementation, four analyte sensing layers and plasmonic materials such as gold (Au) and gold (Au) with Tantalum Pentoxide (Ta2O5) are placed on the exterior of the four arms of the square shaped structure. The sensor's structure consists of only nine circular air holes, making it simple and easy to fabricate using currently available technologies. Finite element method (FEM) based numerical analysis is used to evaluate the sensing performance of the proposed sensor. With optimum structure parameters, the sensor achieves maximum wavelength sensitivity of 11000, 25000, 11000 and 25000 nm/RIU for Channel-1, Channel-2, Channel-3, and Channel-4 respectively. It shows maximum amplitude sensitivity of 803.732, 709.171, 803.827, 709.146 RIU -1 for Channel 1, 2, 3, and 4 respectively. It also shows maximum FOM of 232.55, 352.36, 231.57, 352.36 RIU -1 in Ch-1, Ch-2, Ch-3 and Ch-4 respectively. Moreover, the proposed sensor shows a wide range of refractive index sensing capability from 1.30 to 1.41. Due to multi-analyte detection capability, large sensing range, and excellent sensitivity the proposed sensor unfolds unrivalled capacity of detecting chemicals, carcinogenic agents, biomolecules, and other analytes.

Therapy-related acute lymphoblastic leukaemia in women with antecedent breast cancer.

Therapy-related acute lymphoblastic leukaemia (tr-ALL) is a disease entity attributed to previous exposure to chemotherapy and/or radiation for antecedent malignancy. There is observed female predominance for tr-ALL, likely due to high prevalence and excellent curable rate for non-metastatic breast cancer as well as the frequent use of carcinogenic agents as part of adjuvant therapy. Here, we reviewed 37 women with diagnosis of ALL following breast cancer treatment with focus on cytogenetic categorization. Philadelphia chromosome positivity (Ph+), KMT2A alterations and other cytogenetic change groups were observed in 32%, 22% and 46% of patients respectively. Median overall survival (OS) and relapse-free survival (RFS) were 19.4 and 12.9 months, overall while both OS and RFS were superior in tr-ALL with Ph+ disease compared to KMT2Ar and other cytogenetics respectively. Seventeen (45.9%) patients underwent consolidative allogeneic haematopoietic cell transplantation (alloHCT) in CR1 out of which 4 (24%) relapsed following transplant. Both OS and RFS were superior in the KMT2Ar cytogenetics group following alloHCT. Ph chromosome represents the largest genetic entity of tr-ALL following breast cancer therapy, and it may be associated with superior survival outcomes while KMT2Ar may be associated with poorer outcomes that can perhaps be mitigated by alloHSCT.

Exceptionally High Perfluorooctanoic Acid Uptake in Water by a Zirconium-Based Metal-Organic Framework through Synergistic Chemical and Physical Adsorption.

Perfluorooctanoic acid (PFOA) is an environmental contaminant ubiquitous in water resources, which as a xenobiotic and carcinogenic agent, severely endangers human health. The development of techniques for its efficient removal is therefore highly sought after. Herein, we demonstrate an unprecedented zirconium-based MOF (PCN-999) possessing Zr6 and biformate-bridged (Zr6)2 clusters simultaneously, which exhibits an exceptional PFOA uptake of 1089 mg/g (2.63 mmol/g), representing a ca. 50% increase over the previous record for MOFs. Single-crystal X-ray diffraction studies and computational analysis revealed that the (Zr6)2 clusters offer additional open coordination sites for hosting PFOA. The coordinated PFOAs further enhance the interaction between coordinated and free PFOAs for physical adsorption, boosting the adsorption capacity to an unparalleled high standard. Our findings represent a major step forward in the fundamental understanding of the MOF-based PFOA removal mechanism, paving the way toward the rational design of next-generation adsorbents for per- and polyfluoroalkyl substance (PFAS) removal.

Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation.

Non-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox balancing of the encapsulated nanoparticles (NP) for the maintenance of a homeostatic condition. The formation of Cr-NP complex as an excretion of the heavy metal is also demonstrated through optical spectroscopic and high resolution transmission optical microscopy (HRTEM). Our studies confirm the oxidative stress mitigation activity of the Cr-NP complex. A detailed immunological assay followed by histopathological studies and assessment of mitochondrial parameters in pre-clinical mice model with chromium (Cr) induced lung inflammation establishes the mechanism of drug action to be redox-buffering. Thus, localised delivery of C-Mn3O4 NPs in the respiratory tract via aerosols can act as an effective nanotherapeutic agent against oxidative stress induced lung inflammation.