Toxicokinetics of α- and ß-amanitin in mice following single and combined administrations: Simulating in vivo amatoxins processes in clinical cases.

α-Amanitin and ß-amanitin, two of the most toxic amatoxin compounds, typically coexist in the majority of Amanita mushrooms. The aim of this study was to use a newly developed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method to determine the toxicokinetics and tissue distribution of α- and ß-amanitin following single or combined oral (po) administration in mice. α-Amanitin and ß-amanitin administered at 2 or 10 mg/kg doses showed similar toxicokinetic profiles, except for peak concentration (Cmax). The elimination half-life (t1/2) values of α-amanitin and ß-amanitin in mice were 2.4-2.8 h and 2.5-2.7 h, respectively. Both α- and ß-amanitin were rapidly absorbed into the body, with times to reach peak concentration (Tmax) between 1.0 and 1.5 h. Following single oral administration at 10 mg/kg, the Cmax was significantly lower for α-amanitin (91.1 µg/L) than for ß-amanitin (143.1 µg/L) (p < 0.05). The toxicokinetic parameters of α-amanitin, such as t1/2, mean residence time (MRT), and volume of distribution (Vz/F) and of ß-amanitin, such as Vz/F, were significantly different (p < 0.05) when combined administration was compared to single administration. Tissues collected at 24 h after po administration revealed decreasing tissue distributions for α- and ß-amanitin of intestine > stomach > kidney > lung > spleen > liver > heart. The substantial distribution of toxins in the kidney corresponds to the known target organs of amatoxin poisoning. The content in the stomach, liver, and kidney was significantly higher for of ß-amanitin than for α-amanitin at 24 h following oral administration of a 10 mg/kg dose. No significant difference was detected in the tissue distribution of either amatoxin following single or combined administration. After po administration, both amatoxins were primarily excreted through the feces. Our data suggest the possibility of differences in the toxicokinetics in patients poisoned by mushrooms containing both α- and ß-amanitin than containing a single amatoxin. Continuous monitoring of toxin concentrations in patients' blood and urine samples is necessary in clinical practice.

Genetic Contributions on Attachment in Emerging Adults: Cumulative Effects of Serotonergic Polymorphisms.

Attachment in emerging adults is closely intertwined with emotion regulation, stress coping, and social bonding during the transition from childhood to early adulthood. Due to the critical roles of serotonin in these mental functions, this research explored whether the cumulative genetic effects of serotonergic polymorphisms are associated with individual differences and contextual variations in attachment dimensions over time in emerging adults. Study 1 utilized a cross-sectional design in college students (N = 1088, mean age = 22.71 ± 2.86 years). The results showed significant correlations between a higher cumulative genetic score and elevated levels of attachment anxiety and avoidance. Study 2 employed a three-wave longitudinal design in a cohort of freshmen (N = 523, mean age = 19.54 ± 1.86 years at wave 1). The results demonstrated that a higher genetic score was associated with both higher levels and greater variability in attachment dimensions compared to a lower genetic score. These findings suggest that the cumulative genetic effects of serotonergic polymorphisms contribute to individual differences and dynamic processes in attachment dimensions in emerging adults.

Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation.

Objective: In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods: Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results: At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion: Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.

circFAM193B interaction with PRMT6 regulates AML leukemia stem cells chemoresistance through altering the oxidative metabolism and lipid peroxidation.

Most forms of chemotherapy for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), as their underlying mechanisms remain unclear. Here, we have identified circFAM193B, which regulates the redox biology of LSCs and is associated with unfavorable outcomes in AML patients. In vitro and in vivo assays suggested that circFAM193B significantly inhibits LSCs chemotherapy resistance and AML progression. Knockdown circFAM193B enhances mitochondrial OXPHOS function and inhibits the accumulation of reactive oxygen species and lipid peroxidation mediated by chemotherapy, which protects AML cells from oxidative stress-induced cell death. Mechanistically, circFAM193B physically interacts with arginine methyltransferase PRMT6 catalytic domain and enhances the transcription efficiency of key lipid peroxidation factor ALOX15 by decreasing H3R2me2a modification. In summary, we have identified circFAM193B was downregulated in LSCs to promote the survival of LSC by modulating energy metabolism and the redox balance in the postchemotherapy persistence of LSC. Our studies provide a conceptual advance and biological insights regarding the drug resistance of LSCs via circRNA mediated PRMT6-deposited methylarginine signaling.

Propionate promotes ferroptosis and apoptosis through mitophagy and ACSL4-mediated ferroptosis elicits anti-leukemia immunity.

Short-chain fatty acids (SCFAs), particularly propionate and butyrate, have been reported in many cancers. However, the relationship between propionate and acute myeloid leukemia (AML) remains unclear. Additionally, Acyl-CoA synthetase long chain family member 4 (ACSL4) has been reported to regulate immunity in solid tumors, but there are still many gaps to be filled in AML. Here, we discovered the underlying mechanism of propionate and ACSL4-mediated ferroptosis for immunotherapy. Our results showed that the level of propionate in the AML patients' feces was decreased, which was correlated to gut microbiota dysbiosis. Moreover, we demonstrated that propionate suppressed AML progression both in vivo and in vitro. In mechanism, propionate induced AML cells apoptosis and ferroptosis. The imbalance of reactive oxygen species (ROS) and redox homeostasis induced by propionate caused mitochondrial fission and mitophagy, which enhanced ferroptosis and apoptosis. Furthermore, ACSL4-mediated ferroptosis caused by propionate increased the immunogenicity of AML cells, induced the release of damage-associated molecular patterns (DAMPs), and promoted the maturation of dendritic cells (DCs). The increased level of immunogenicity due to ferroptosis enable propionate-based whole-cell vaccines to activate immunity, thus further facilitating effective killing of AML cells. Collectively, our study uncovers a crucial role for propionate suppresses AML progression by inducing ferroptosis and the potential mechanisms of ACSL4-mediated ferroptosis in the regulation of AML immunity.

Mitochondrial transfer in hematological malignancies.

Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy. In this review, we discuss the patterns and mechanisms on mitochondrial transfer and their engagement in different pathophysiological contexts and outline the latest knowledge on intercellular transport of mitochondria in hematological malignancies. Besides, we briefly outline the drug resistance mechanisms caused by mitochondrial transfer in cells during chemotherapy. Our review demonstrates a theoretical basis for mitochondrial transfer as a prospective therapeutic target to increase the treatment efficiency in hematological malignancies and improve the prognosis of patients.

Hematopoietic stem cells suppress proliferation and enhance differentiation of leukemia cells through regulating apoptotic and inflammatory genes.

PURPOSE: Stem cells are known to play an important role in tumor treatment and many of them have shown tumor-suppressing ability in different cancers; however, whether hematopoietic stem cells (HSCs) have growth-inhibiting effects on leukemia cells has not been fully evaluated. Herein, we aimed to demonstrate the growth-restraining function of HSCs in acute leukemia treatment. METHODS: Cell fusion experiment was conducted by PEG-1500. The viability, proliferation, apoptosis and differentiation of leukemia cells were evaluated by cell counting, CCK-8 and flow cytometry analysis. The morphological changes were imaged using a fluorescence microscope. The expression of genes was detected by quantitative reverse transcription PCR (qRT-PCR). RESULTS: We observed that HSCs and their lytic extracts had the capability to suppress leukemia cells proliferation, promote apoptosis and especially induce acute myelogenous leukemia (AML) cells differentiation, which might have an effect on differentiation therapy to leukemia especially AML treatment. The expression levels of Bcl-2, Survivin decreased and Bax increased following HSCs extracts treatment. Furthermore, the expression of inflammatory cytokines also changed in AML cells which might have to do with the mechanism of HSCs/extracts suppressing effect. CONCLUSION: HSCs and their extracts can suppress the proliferation of leukemia cells and enhance the differentiation of AML cells and using the extracts of HSCs might be a probable therapeutic option for acute leukemia.

Hair-based rapid UPLC-MS/MS analysis of 36 phencyclidine-type substances in forensic cases.

Phencyclidine (PCP) is a frequently abused dissociative agent. It causes confusion, increased tendencies toward violence, and concentration-dependent cytotoxicity after entry into the body. The parent nucleus of phencyclidine-type substances is arylcyclohexylamine, which is easy to modify; therefore, abusers and dealers can readily synthesize substitutes beyond the drug control catalog. An urgent need exists to establish screening methods for phencyclidine-type substances to provide technical support for abuse monitoring. In this study, 20 mg of hair was pulverized in 500 mL of methanol containing 0.5 ng/mL PCP-d5. After ultrasonication, centrifugation, and filtration, the supernatant was analyzed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) operating in the multiple reaction monitoring mode. Phencyclidine-type substances were separated in 13 min on a biphenyl column using a mobile phase gradient composed of A (water, formic acid 0.1%, acetonitrile 5%, 20 mmol/L ammonium acetate) and B (acetonitrile). The developed and validated method showed good selectivity, sensitivity (limit of detection: 0.25-2 pg/mg and lower limit of quantitation: 0.5-4 pg/mg), linearity (R2 > 0.994), accuracy, and precision (< 20%), and a dilution effect. The method also showed good recovery and acceptable matrix effects for most of the targeted compounds. This analytical approach was successfully applied for the identification and quantification of phencyclidine-type substances in hair from 87 authentic forensic cases. Nine analytes were detected: ketamine (10.3-26211.3 pg/mg), 2-F-2-oxo-PCE (11.5-4034.9 pg/mg), 2-FDCK (14.0-43290.2 pg/mg), 2-BrDCK (10.6-21170.0 pg/mg), nor2-FDCK (10.1-16767.4 pg/mg), tiletamine (10.1-3250.8 pg/mg), O-PCE (43.3-166.1 pg/mg), DCK (10.2-90.4 pg/mg), and norDCK (24.9-103.0 pg/mg).

The genetic polymorphisms of immune-related genes contribute to the susceptibility and survival of lymphoma.

BACKGROUND: Though immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear. METHODS: We investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune-related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA. RESULTS: By comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK-STAT, NF-κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter-OS genotypes. CONCLUSIONS: We used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune-related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway.

Aberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML); however, its regulatory mechanism remains unclear. Herein, we identified a novel circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We further validated their expression in large-scale samples and found that only the expression of Circ_0001187 was significantly decreased in newly diagnosed (ND) AML patients and increased in patients with hematological complete remission (HCR) compared with controls. Knockdown of Circ_0001187 significantly promoted proliferation and inhibited apoptosis of AML cells in vitro and in vivo, whereas overexpression of Circ _0001187 exerted the opposite effects. Interestingly, we found that Circ_0001187 decreases mRNA m6A modification in AML cells by enhancing METTL3 protein degradation. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression of E3 ubiquitin ligase RNF113A, which mediates METTL3 ubiquitin/proteasome-dependent degradation via K48-linked polyubiquitin chains. Moreover, we found that the low expression of Circ _0001187 is regulated by promoter DNA methylation and histone acetylation. Collectively, our findings highlight the potential clinical implications of Circ _0001187 as a key tumor suppressor in AML via the miR-499a-5p/RNF113A/METTL3 pathway.

Clinical and prognostic profile of SRSF2 and related spliceosome mutations in patients with acute myeloid leukemia.

BACKGROUND: Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but their clinical and prognostic relevance in acute myeloid leukemia (AML) have rarely been reported. METHODS: A total of 368 newly diagnosed non-M3 AML patients were included in this study. Next generation sequencing including four SF genes was performed on the genomicDNA. The clinical features and survival were analyzed using statistical analysis. RESULTS: We found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequently found in older or male patients. SRSF2 mutations were shown obviously co-existed with IDH2 mutation. The level of measurable residual disease after first chemotherapy was higher in SF-mutated patients compared to that in SF-wild patients, while the complete remission rate was significantly decreased. And the overall survival of SF-mutated patients was shorter than that of SF-wild patients. Moreover, our multivariable analysis suggests that the index of male, Kit mutation or ZRSR2 mutation was the independent risk factor for overall survival. SRSF2mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by flow cytometry. CONCLUSION: SF mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2mut could be potential targets for novel treatment in AML.

Smart and Generalizable Cytarabine Derivative-Triggered Nanoparticles for Synergistic Therapy of Relapsed/Refractory Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is rapidly progressed hematologic malignancy with relapsed and refractory characteristics. Cytarabine combined with the BCL2 inhibitor venetoclax showed impressive response rates in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML), while it requires complicated administration regimens and brings added toxicity. In this work, we synthesized a mercaptopropionic acid-substituted derivative of Ara-C (Ara-SH) and used it as the trigger to fabricate a smart cytarabine and venetoclax-coloaded nanoparticle (AV-NP) through self-assembly. The AV-NP characterized with redox-responsive drug release, rapid uptake by leukemia cells, and long retention in circulation had the potential to accumulate in leukemia-enriched sites. It generated a remarkable synergistic effect with higher antileukemia activity in vitro and better safety in the hematologic system compared with free drugs and significantly improved the therapeutic effect on orthotopic AML mice in vivo. These similar results were also confirmed in primary cells from R/R-AML patients. Besides, the AV-NP has the superiority of facile fabrication and generalizability, rendering it easy for clinical translation.

Mechanistic and microbial ecological insights into the impacts of micro- and nano- plastics on microbial reductive dehalogenation of organohalide pollutants.

Micro- and nano-plastics are prevalent in diverse ecosystems, but their impacts on biotransformation of organohalide pollutants and underpinning microbial communities remain poorly understood. Here we investigated the influence of micro- and nano-plastics on microbial reductive dehalogenation at strain and community levels. Generally, microplastics including polyethylene (PE), polystyrene (PS), polylactic acid (PLA), and a weathered microplastic mixture increased dehalogenation rate by 10 - 217% in both the Dehalococcoides isolate and enrichment culture, whereas the effects of polyvinyl chloride (PVC) and a defined microplastic mixture depended on their concentrations and cultures. Contrarily, nano-PS (80 nm) consistently inhibited dehalogenation due to increased production of reactive oxygen species. Nevertheless, the enrichment culture showed higher tolerance to nano-PS inhibition, implying crucial roles of non-dehalogenating populations in ameliorating nanoplastic inhibition. The variation in dehalogenation activity was linked to altered organohalide-respiring bacteria (OHRB) growth and reductive dehalogenase (RDase) gene transcription. Moreover, microplastics changed the community structure and benefited the enrichment of OHRB, favoring the proliferation of Dehalogenimonas. More broadly, the assembly of microbial communities on plastic biofilms was more deterministic than that in the planktonic cells, with more complex co-occurrence networks in the former. Collectively, these findings contribute to better understanding the fate of organohalides in changing environments with increasing plastic pollution.

Bright side of the MAOA-uVNTR on trait and situational forgiveness.

The stress-and-coping theory of forgiveness posits that forgiveness and aggression are alternative ways of coping with stress of interpersonal offences. Inspired by the link between aggression and MAOA-uVNTR (a genetic variant involving in catabolism of monoamines), we investigated the relationship between this variant and forgiveness with two studies. Study 1 examined the relationship between the MAOA-uVNTR and trait forgiveness in students, and study 2 examined the effect of this variant on third-party forgiveness in response to situational offences in male inmates. The results showed that the MAOA-H (a high activity allele) was associated with higher trait forgiveness in male students and greater third-party forgiveness to accidentally committed harm and attempted but failed harm in male inmates than the MAOA-L. These findings highlight the bright side of MAOA-uVNTR on trait and situational forgiveness.

Resilience and functional redundancy of methanogenic digestion microbiome safeguard recovery of methanogenesis activity under the stress induced by microplastics.

Microplastics and nanoplastics are emerging pollutants that substantially influence biological element cycling in natural ecosystems. Plastics are also prevalent in sewage, and they accumulate in waste-activated sludge (WAS). However, the impacts of plastics on the methanogenic digestion of WAS and the underpinning microbiome remain underexplored, particularly during long-term operation. In this study, we found that short-term exposure to individual microplastics and nanoplastics (polyethylene, polyvinyl chloride, polystyrene, and polylactic acid) at a low concentration (10 particles/g sludge) slightly enhanced methanogenesis by 2.1%-9.0%, whereas higher levels (30-200 particles/g sludge) suppressed methanogenesis by 15.2%-30.1%. Notably, the coexistence of multiple plastics, particularly at low concentrations, showed synergistic suppression of methanogenesis. Unexpectedly, methanogenesis activity completely recovered after long-term exposure to plastics, despite obvious suppression of methanogenesis by initial plastic exposure. The inhibition of methanogenesis by plastics could be attributed to the stimulated generation of reactive oxygen species. The stress induced by plastics dramatically decreased the relative abundance of methanogens but showed marginal influence on putative hydrolytic and fermentation populations. Nonetheless, the digestion sludge microbiome exhibited resilience and functional redundancy, contributing to the recovery of methanogenesis during the long-term operation of digesters. Plastics also increased the complexity, modularity, and negative interaction ratios of digestion sludge microbiome networks, but their influence on community assembly varied. Interestingly, a unique plastisphere was observed, the networks and assembly of which were distinct from the sludge microbiome. Collectively, the comprehensive evaluation of the influence of microplastics and nanoplastics on methanogenic digestion, together with the novel ecological insights, contribute to better understanding and manipulating this engineered ecosystem in the face of increasing plastic pollution.

Construction of a Clinical Predictive Model of Left Atrial and Left Atrial Appendage Thrombi in Patients with Nonvalvular Atrial Fibrillation.

Background: The purpose of this study was to investigate the risk factors of left atrial (LA) or left atrial appendage (LAA) thrombi in patients with nonvalvular atrial fibrillation (NVAF) and to establish and validate relevant predictive models. It might improve thromboembolic risk stratification in patients with NVAF. Methods: This study retrospectively included 1210 consecutive patients with NVAF undergoing transesophageal echocardiography (TEE), of whom 139 patients had thrombi in LA or in LAA. Through literature review and the ten events per variable (10EPV) principle, 13 variables were finally identified for inclusion in multivariate analysis. Models were constructed by multivariate logistic stepwise regression and least absolute shrinkage and selection operator (lasso) regression. Results: After logistic regression, five variables (AF type, age, B-type natriuretic peptide, E/e' ratio, and left atrial diameter) were finally screened out as model 1. After Lasso regression, AF type, age, gender, B-type natriuretic peptide, E/e' ratio, left atrial diameter, and left ventricular ejection fraction were finally screened as model 2. After comparing the two models, the simpler model 1 was finally selected. The area under the ROC curve (AUC) of the model 1 was 0.865 (95% CI: 0.838-0.892), the Hosmer-Lemeshow test = 0.898, and the AUC = 0.861 after internal validation. The clinical decision curve showed that the new clinical prediction model could achieve a net clinical benefit when the expected threshold was between 0 and 0.6. Conclusion: This study constructed a new clinical prediction model of LA or LAA thrombi, with a higher discriminative degree than the CHADS2 and CHA2DS2-VASc scoring systems (AUC: 0.865 vs. 0.643; AUC: 0.865 vs 0.652).

Crosstalk between regulated necrosis and micronutrition, bridged by reactive oxygen species.

The discovery of regulated necrosis revitalizes the understanding of necrosis from a passive and accidental cell death to a highly coordinated and genetically regulated cell death routine. Since the emergence of RIPK1 (receptor-interacting protein kinase 1)-RIPK3-MLKL (mixed lineage kinase domain-like) axis-mediated necroptosis, various other forms of regulated necrosis, including ferroptosis and pyroptosis, have been described, which enrich the understanding of pathophysiological nature of diseases and provide novel therapeutics. Micronutrients, vitamins, and minerals, position centrally in metabolism, which are required to maintain cellular homeostasis and functions. A steady supply of micronutrients benefits health, whereas either deficiency or excessive amounts of micronutrients are considered harmful and clinically associated with certain diseases, such as cardiovascular disease and neurodegenerative disease. Recent advance reveals that micronutrients are actively involved in the signaling pathways of regulated necrosis. For example, iron-mediated oxidative stress leads to lipid peroxidation, which triggers ferroptotic cell death in cancer cells. In this review, we illustrate the crosstalk between micronutrients and regulated necrosis, and unravel the important roles of micronutrients in the process of regulated necrosis. Meanwhile, we analyze the perspective mechanism of each micronutrient in regulated necrosis, with a particular focus on reactive oxygen species (ROS).

Patient-derived primary breast cancer cells and their potential for predicting sensitivity to chemotherapy.

Chemotherapy resistance exposes patients to side effects and delays the effect of therapy in patients. So far, there are no predictive tools to predict resistance to chemotherapy and select sensitive chemotherapeutic drugs for the patient. Here, we aim to develop an in-vitro primary cell culture model from breast cancer patients to predict sensitivity to chemotherapy. We created the primary breast cancer cell medium BCMI and culture system with higher efficiency of the model establishment. Immunofluorescence staining of ERa, PR and HER2 were done to identify the primary breast cancer cell from the counterpart breast cancer patient. The killing assay showed that these primary breast cancer cells responded differently to doxorubicin and pirarubicin treatment. These results indicate that our established primary breast cancer cell model holds great promise for predicting breast cancer sensitivity to chemotherapy drugs.