a-quantitative-assessment-phagocytosis-allogeneic-xenogeneic

A Quantitative Assessment of the Phagocytosis of Allogeneic and Xenogeneic Erythrocytes by Rat Macrophages <em>In Vitro</em>

Xenogeneic cell transplantation often faces significant immune rejection, even in immunodeficient animal models. Among residual immune components, ...

Jiangsu university

The potential mechanism of the chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from acute myeloid leukemia. In a multicenter clinical trial, 38 patients with poor risk forms of AML were treated with tetrandrine (TET), a potent inhibitor of the MDR-1 efflux pump, combined with daunorubicin (DNR), etoposide and cytarabine (TET-DEC). Overall, post-chemotherapy marrow hypoplasia was achieved in 36 patients. Sixteen patients (42%) achieved complete remission or restored chronic phase, 9 achieved partial remission (PR) and 13 failed therapy. Toxicities included infection, myelosuppression, stomatitis, mucositis, cerebellar toxicity and reversible cardiotoxicity. There was no significant difference in response for P-gp-positive and -negative patients. P-gp function was assessed in 26 patients by flow cytometric analysis, TET-contained plasma-augmented DNR accumulation relative to pretreatment plasma in K562/A02 cells by a median value of 88+/-101% (range, 11-501%). However, there was no difference in DNR uptake between responding and non-responding patients. Our data showed that TET-DEC was relatively well tolerated in these patients with poor risk AML, and had encouraging antileukemic effects.

Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia.

In this study, we have explored the possibility of the combination of the high reactivity of nano Fe3O4 or Au nanoparticles and daunomycin, one of the most important antitumor drugs in the treatment of acute leukemia clinically, to inhibit MDR of K562/A02 cells. Initially, to determine whether the magnetic nanoparticle Fe3O4 and Au can facilitate the anticancer drug to reverse the resistance of cancer cells, we have explored the cytotoxic effect of daunomycin (DNR) with and without the magnetic nano-Fe3O4 or nano-Au on K562 and K562/A02 cells by MTT assay. Besides, the intracellular DNR concentration and apoptosis of the K562/A02 cells was further investigated by flow cytometry and confocal fluorescence microscopic studies. The MDR1 gene expression of the K562/A02 cells was also studied by RT-PCR method. Our results indicate that 5.0 x 10(-7) M nano-Fe3O4 or 2.0 x 10(-8) M nano-Au is biocompatible and can apparently raise the intracellular DNR accumulation of the K562/A02 cells and increase the apoptosis of tumor cells. Moreover, our observations illustrate that although these two kinds of nanoparticles themselves could not lower the MDRI gene expression of the K562/A02 cells, yet they could degrade the MDR1 gene level when combining with anticancer drug DNR. This raises the possibility to combine the nano-Fe3O4 or nano-Au with DNR to reverse the drug resistance of K562/A02 cells, which could offer a new strategy for the promising efficient chemotherapy of the leukemia patients.

Synergistic effect of the combination of nanoparticulate Fe3O4 and Au with daunomycin on K562/A02 cells.

Apoptosis is a common pathway that finally mediated the killing functions of anticancer drugs, which is an important cause of multidrug resistance (MDR). The aim of this study was to investigate the potential benefit of combination therapy with magnetic nanoparticle of Fe(3)O(4) (MNP(Fe(3)O(4))) and 5-bromotetrandrin (BrTet). Analysis of the apoptosis percentage showed that combination of daunorubicin (DNR) with either MNP(Fe(3)O(4)) or BrTet exerted a potent cytotoxic effect on K562/A02 cells, while MNP(Fe(3)O(4)) and BrTet cotreatment can synergistically enhance DNR-induced apoptosis. Importantly, we confirmed that the distinct synergism effect of that composite on reverse multidrug resistance may owe to the regulation of various proliferative and antiapoptotic gene products, including P53 and caspase-3. Thus our in vitro data strongly suggests a potential clinical application of MNP(Fe(3)O(4)) and BrTet combination on CML.

Magnetic nanoparticle of Fe3O4 and 5-bromotetrandrin interact synergistically to induce apoptosis by daunorubicin in leukemia cells.

In this paper we establish the xenograft leukemia model with stable multidrug resistance in nude mice and to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe(3)O(4) (MNP-Fe(3)O(4)) combined with daunorubicin (DNR) in vivo. Two subclones of K562 and K562/A02 cells were inoculated subcutaneously into the back of athymic nude mice (1 x 10(7) cells/each) respectively to establish leukemia xenograft models. Drug-resistant and sensitive tumor-bearing nude mice were assigned randomly into five groups which were treated with normal saline; DNR; NP-Fe(3)O(4) combined with DNR; 5-BrTet combined with DNR; 5-BrTet and MNP-Fe(3)O(4) combined with DNR, respectively. The incidence of formation, growth characteristics, weight, and volume of tumors were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of Bcl-2, and BAX were detected by Western blot. Bcl-2, BAX, and caspase-3 genes were also detected. For K562/A02 cells xenograft tumors, 5-BrTet and MNP-Fe(3)O(4) combined with DNR significantly suppressed growth of tumor. A histopathologic examination of tumors clearly showed necrosis of the tumors. Application of 5-BrTet and MNP-Fe(3)O(4) inhibited the expression of Bcl-2 protein and upregulated the expression of BAX and caspase-3 proteins in K562/A02 cells xenograft tumor. It is concluded that 5-BrTet and MNP-Fe(3)O(4) combined with DNR had a significant tumor-suppressing effect on a MDR leukemia cells xenograft model.

Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice.

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy. We evaluated the effect of daunorubicin (DNR)-loaded magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) on K562-n/VCR cells in vivo. K562-n and its MDR counterpart K562-n/VCR cell were inoculated into nude mice subcutaneously. The mice were randomly divided into four groups: group A received normal saline, group B received DNR, group C received MNPs-Fe3O4, and group D received DNR-loaded MNPs-Fe3O4. For K562-n/VCR tumor, the weight was markedly lower in group D than that in groups A, B, and C. The transcriptions of Mdr-1 and Bcl-2 gene were significantly lower in group D than those in groups A, B, and C. The expression of Bcl-2 was lower in group D than those in groups A, B, and C, but there was no difference in the expression of P-glycoprotein. The transcriptions and expressions of Bax and caspase-3 in group D were increased significantly when compared with groups A, B, and C. In conclusion, DNR-loaded MNPs-Fe3O4 can overcome MDR in vivo.

Daunorubicin-loaded magnetic nanoparticles of Fe3O4 overcome multidrug resistance and induce apoptosis of K562-n/VCR cells in vivo.

Gambogic acid (GA) has a significant anticancer effect on a wide variety of solid tumors. Recently, many nanoparticles have been introduced as drug-delivery systems to enhance the efficiency of anticancer drug delivery. The aim of this study was to investigate the potential benefit of combination therapy with GA and magnetic nanoparticles of Fe(3)O(4) (MNPs-Fe(3)O(4)). The proliferation of K562 cells and their cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscope and flow cytometry, respectively. Furthermore, real-time polymerase chain reaction and Western blotting analyses were performed to examine gene transcription and protein expression, respectively. The results showed that MNPs-Fe(3)O(4) dramatically enhanced GA-induced cytotoxicity and apoptosis in K562 cells. The typical morphological features of apoptosis treated with GA and MNPs-Fe(3)O(4) were observed under an optical microscope and a fluorescence microscope, respectively. The transcription of caspase-3 and bax gene in the group treated with GA and MNPs-Fe(3)O(4) was higher than that in the GA-alone group or MNPs-Fe(3)O(4)-alone group, but the transcription of bcl-2, nuclear factor-kappaB, and survivin degraded as did the expression of corresponding proteins in K562 cells. Our data suggests a potential clinical application of a combination of GA and MNPs-Fe(3)O(4) in leukemia therapy.

Synergistic effect of magnetic nanoparticles of Fe(3)O(4) with gambogic acid on apoptosis of K562 leukemia cells.

In many instances, multidrug resistance (MDR) is mediated by increasing the expression at the cell surface of the MDR1 gene product, P-glycoprotein (P-gp), a 170-kD energy-dependent efflux pump. The aim of this study was to investigate the potential benefit of combination therapy with magnetic Fe(3)O(4) nanoparticle [MNP (Fe(3)O(4))] and MDR1 shRNA expression vector in K562/A02 cells. For stable reversal of "classical" MDR by short hairpin RNA (shRNA) aiming directly at the target sequence (3491-3509, 1539-1557, and 3103-3121 nucleotide) of MDR1 mRNA. PGC silencer-U6-neo-GFP-shRNA/MDR1 called PGY1-1, PGY1-2, and PGY1-3 were constructed and transfected into K562/A02 cells by lipofectamine 2000. After transfected and incubated with or without MNP (Fe(3)O(4)) for 48 hours, the transcription of MDR1 mRNA and the expression of P-gp were detected by quantitative real-time PCR and Western-blot assay respectively. Meanwhile intracellular concentration of DNR in K562/A02 cells was detected by flow cytometry (FCM). PGC silencer-U6-neo-GFP-shRNA/MDR1 was successfully constructed, which was confirmed by sequencing and PGY1-2 had the greatest MDR1 gene inhibitory ratio. Analysis of the reversal ratio of MDR, the concentration of daunorubicin (DNR) and the transcription of MDR1 gene and expression of P-gp in K562/A02 showed that combination of DNR with either MNP (Fe(3)O(4)) or PGY1-2 exerted a potent cytotoxic effect on K562/A02 cells, while combination of MNP (Fe(3)O(4)) and PGY1-2 could synergistically reverse multidrug resistance. Thus our in vitro data strongly suggested that a combination of MNP (Fe(3)O(4)) and shRNA expression vector might be a more sufficient and less toxic anti-MDR method on leukemia.

Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and MDR1 shRNA expression vector in leukemia cells.

In the title compound, C19H19ClO4, the di-hydro-pyran ring and the cyclo-hexane ring adopt a half-chair conformation and a chair conformation, respectively. The cyclo-hexene ring has an envelope conformation with the central CH2 C atom as the flap. This atom is disordered over two positions [site-occupancy ratio = 0.744 (12):0.256 (12)] above and below the mean plane formed by the other five atoms. In the crystal, O-H⋯O hydrogen bonds between hy-droxy and carbonyl groups link mol-ecules into chains propagating along [001].

9-(2-Chloro-phen-yl)-4a-hy-droxy-3,4,4a,5,6,7,9,9a-octa-hydro-2H-xanthene-1,8-dione.

Modulation of Immune check point regulators, especially the PD-1/PD-L1 axis, plays a critical role in successful management of a small proportion of lung cancer patients, but not so effective in the rest of lung cancer patients. A better understanding of immunotherapy non-responsive or resistant patients therefore warranted for future development of novel therapeutics. The newly identified regulator CMTM6 (CKLF-like MARVEL transmembrane domain containing 6) has been reported to serves as the stabilizer of PD-L1 and enhances the inhibitory effect of PD-L1 on immune system in both cell line and animal models, but its clinical relevance associated with PD-L1 is unknown and the current study is designed to address this question. The study using immunohistochemistry demonstrated that CMTM6 positivity from 15 out of 19 types of cancers with our in-house tissue microarray, and PD-L1 expression is always found only in CMTM6 positive cancers. CMTM6 and PD-L1 expression were analyzed in 81 lung cancer patient sample, and we observed that CMTM6 expression correlated with cancer histotypes and inversely correlated with cancer metastases, but not with patients' age and gender. No PD-L1 expression was observed in negative CMTM6 samples. Higher expression PD-L1 is also associated with higher CMTM6 expression. In summary, CMTM6 expression is associated with PD-L1 expression, as well as lung cancer histotypes and metastasis. The results thus for the first time confirmed earlier reports on CMTM6/PD-L1 connection, from a clinical aspect of analysis.

CMTM6, the newly identified PD-L1 regulator, correlates with PD-L1 expression in lung cancers.

To explore radiomic features of pharmacokinetic dynamic contrast-enhanced (Pk-DCE) MRI on the extensive Tofts model to diagnose breast cancer and predict molecular phenotype. Breast lesions enrolled must undergo Pk-DCE MRI before treatment or puncture, and be identified as primary lesions by pathology. K, K, V and V were generated on the extensive Tofts model. Radiomic features (histogram, geometry and texture features) were extracted from parametric maps and selected by LASSO. The subjects were divided into training and validation cohort with a ratio of 4:1 to construct model in diagnosis of breast cancer. Feature analysis was made to predict the molecular phenotype. Area under curve (AUC), sensitivity, specificity and accuracy were used to evaluate radiomic features. DeLong's test was performed to compare AUC values. 228 breast lesions met the criteria were used to discrimination and 126 malignant lesions were used to study molecular phenotypes. The number of training cohort and validation cohort were 182 and 46, respectively. The AUC of K, K, V, and V was 0.95, 0.93, 0.89, and 0.96, and their accuracy was 85%, 89%, 89%, 94% respectively in diagnosis of breast lesions, while their AUC was 0.71 to 0.77, 0.61 to 0.68, and 0.67 to 0.74 to predict ER/PR, Her-2, and Ki-67. There was no significant difference among parameters (P > 0.05). Radiomic features based on Pk-DCE MRI have an advantage to diagnose breast cancer and less ability to predict molecular phenotypes, which are beneficial to guide clinical treatment of breast lesions in some extent.

Radiomic features of Pk-DCE MRI parameters based on the extensive Tofts model in application of breast cancer.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for  autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Owing to its nice performance, low cost, and simple solution-processing, organic-inorganic hybrid perovskite solar cell (PSC) becomes a promising candidate for next-generation high-efficiency solar cells. The power conversion efficiency (PCE) has boosted from 3.8% to 25.2% over the past ten years. Despite the rapid progress in PCE, the device stability is a key issue that impedes the commercialization of PSCs. Recently, all-inorganic cesium lead halide perovskites have attracted much attention due to their better stability compared with their organic-inorganic counterpart. In this progress report, we summarize the properties of CsPb(IBr) and their applications in solar cells. The current challenges and corresponding solutions are discussed. Finally, we share our perspectives on CsPb(IBr) solar cells and outline possible directions to further improve the device performance.

CsPb(IBr) solar cells.

Mesenchymal stem/stromal cells （MSCs） act as a factor in tumor recurrence after drug treatment with their involvement observed in various cancer types. As a constituent of the tumor microenvironment (TME), MSCs not only provide support to tumor growth but also establish connections with diverse cell populations within the TME, serving as mediators linking different tumor-associated components. MSCs play an important role in maintaining tumor progression due to their stem cell properties and remarkable differentiation capacity. Given the intensification of tumor research and the encouraging results achieved in recent years，the aim of this article is to investigate the supportive role of MSCs in tumor cells as well as in various cellular and non-cellular components of the tumor microenvironment. Furthermore, the article shows that MSCs do not have a specific anatomical ecological niche and describes the contribution of MSCs to the maintenance of tumor homeostasis on the basis of homing, plasticity and tumor-forming properties. By elucidating the critical roles of different components of TME, this study provides a comprehensive understanding of tumor therapy and may offer new insights into defeating cancer.

Mesenchymal stem/stromal cells: dedicator to maintain tumor homeostasis.

Helmets are crucial for protecting motorcycle riders from head injuries in accidents. This study proposes a helmet pad design based on a negative-Poisson's-ratio (NPR) structure and comprehensively evaluates its protective effect on head injuries. A concave hexagonal honeycomb structure was embedded into the energy-absorbing lining of a motorcycle helmet, and finite element collision simulations were conducted according to the ECE R22.05 standard. These simulations compared and analyzed the differences in protective performance between concave hexagonal honeycomb helmets with different parameter configurations and traditional expanded polystyrene (EPS) helmets under flat anvil impact scenarios. Using biomechanical parameters, including peak linear acceleration (PLA), head injury criterion (HIC), intracranial pressure (ICP), maximum principal strain (MPS), and the probability of AIS2+ traumatic brain injury, the protective effect of the helmets on traumatic brain injury was evaluated. The results showed that when the wall angle of the honeycomb structure was 60°, honeycomb helmets with wall thicknesses of 0.8 mm and 1.0 mm significantly reduced PLA and HIC values. In particular, the honeycomb helmet with a wall thickness of 1.0 mm reduced ICP by 25.7%, while the honeycomb helmet with a wall thickness of 1.2 mm exhibited the lowest maximum principal strain in the skull compared to EPS helmets and reduced the probability of AIS2+ brain injury by 7.2%. Concave hexagonal honeycomb helmets demonstrated an excellent protective performance in reducing the risk of traumatic brain injury. These findings provide important theoretical foundations and engineering references for the design and optimization of new protective helmets.

Article	Year
Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia. Leukemia research\| PubMed ID: 16219352	2006
Synergistic effect of the combination of nanoparticulate Fe3O4 and Au with daunomycin on K562/A02 cells. International journal of nanomedicine\| PubMed ID: 18990943	2008
Magnetic nanoparticle of Fe3O4 and 5-bromotetrandrin interact synergistically to induce apoptosis by daunorubicin in leukemia cells. International journal of nanomedicine\| PubMed ID: 19421371	2009
Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice. International journal of nanomedicine\| PubMed ID: 19421372	2009
Daunorubicin-loaded magnetic nanoparticles of Fe3O4 overcome multidrug resistance and induce apoptosis of K562-n/VCR cells in vivo. International journal of nanomedicine\| PubMed ID: 19918366	2009
Synergistic effect of magnetic nanoparticles of Fe(3)O(4) with gambogic acid on apoptosis of K562 leukemia cells. International journal of nanomedicine\| PubMed ID: 20011242	2009
Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and MDR1 shRNA expression vector in leukemia cells. International journal of nanomedicine\| PubMed ID: 20957165	2010
9-(2-Chloro-phen-yl)-4a-hy-droxy-3,4,4a,5,6,7,9,9a-octa-hydro-2H-xanthene-1,8-dione. Acta crystallographica. Section E, Structure reports online\| PubMed ID: 24826146	2014
CMTM6, the newly identified PD-L1 regulator, correlates with PD-L1 expression in lung cancers. Biochemistry and biophysics reports\| PubMed ID: 31646201	2019
Radiomic features of Pk-DCE MRI parameters based on the extensive Tofts model in application of breast cancer. Physical and engineering sciences in medicine\| PubMed ID: 32524436	2020
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy\| PubMed ID: 33634751	2021
CsPb(IBr) solar cells. Science bulletin\| PubMed ID: 36659562	2019
Mesenchymal stem/stromal cells: dedicator to maintain tumor homeostasis. Human cell\| PubMed ID: 39607530	2024
Mechanical Performance Evaluation of Negative-Poisson's-Ratio Honeycomb Helmets in Craniocerebral Injury Protection. Materials (Basel, Switzerland)\| PubMed ID: 40428925	2025

Feng Gao

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