Background/Aims: Although the cure rate of acute promyelocytic leukemia (APL) has exceeded 90%, the relapse/refractory APL that resistant to all-trans retinoic acid (ATRA) or ATO was still serious concern. Matrine (MAT) could improve the differentiation ability of ATRA-resistant APL cells. This study aimed to explore how the APL-specific fusion protein was degraded in ATRA-resistant APL with the application of MAT and ATRA. Methods: ATRA-sensitive (NB4) and ATRA-resistant (NB4-LR1) cell lines were used. Nitroblue tetrazolium reduction assay and flow cytometry were used to detect the differentiation ability. The activity of ubiquitin-proteasome and autophagy-mediated pathways in both cells treated with ATRA with or without MAT were compared in protein and mRNA level (Western blot analysis, qRT-PCR), the Fluorescent substrate Suc-LLVY-AMC detection was used to detect the activity of proteasome, and electron microscope for observing autophagosome. MG 132(proteasome inhibitor), rapamycin (autophagy activator), hydroxychloroquine (lysosomal inhibitor) and STI571 [retinoic acid receptor alpha (RARα) ubiquitin stabilizer] were used as positive controls. The effect of MAT was observed in vivo using xenografts. Results: MAT improved the sensitivity of NB4-LR1cells to ATRA treatment, which was consistent with the expression of PML-RARα fusion protein. MAT promoted the ubiquitylation level in NB4-LR1. MG 132 induced the decrease in RARα in both cell lines, and hampered the differentiation of NB4 cells. MAT also promoted the autophagy in NB4-LR1 cells, with an increase in microtubule-associated protein 1 light chain3 (LC3)-II and LC3-II/LC3-I ratio and exhaustion of P62. The expression of LC3II increased significantly in the MAT and ATRA + MAT groups in combination with lysosomal inhibitors. A similar phenomenon was observed in mouse xenografts. MAT induced apoptosis and differentiation. Conclusions: Autophagy and ubiquitin-mediated proteolytic degradation of PML/RARα fusion protein are crucial in MAT-induced differentiation sensitivity recovery of NB4-LR1 cells.
Disseminated Rhizopus microsporus infections are uncommon in children and are resistant to echinocandin and azole antifungal agents. We describe a child with severe aplastic anemia who developed disseminated R. microsporus infection following allogeneic hematopoietic stem cell transplantation. R. microsporus was identified microscopically in the hepatic drain culture and was confirmed on the basis of 18S rRNA and 28S rRNA sequence analyses. The patient was treated successfully with hepatic drainage and amphotericin B deoxycholate.
Treatment with the KBS formulation may reduce the rate of graft failure and treatment-related mortality and improve the rate of OS in SAA patients with allo-HSCT.
Background. Leukemia is a common malignancy that has four main subtypes and is a threat to human health. Understanding the epidemiological status of leukemia and its four main subtypes globally is important for allocating appropriate resources, guiding clinical practice, and furthering scientific research. Methods. Average annual percentage changes (AAPCs) were calculated to estimate the change trends of age-standardized rates (ASRs) from 1990 to 2019 in 204 countries and territories. The risk factors for leukemia death and disability-adjusted life-year (DALY) were also analyzed. In addition, the future trends in ASRs were projected through 2030. Results. The total number of incident cases, deaths, and DALYs from leukemia in 2019 was 0.64, 0.33, and 11.66 million, respectively. Decreasing trends in age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and age-standardized DALY rate were detected on a global level while increasing trends in ASIR were detected in the high-sociodemographic index (SDI) regions. The leukemia burden was heavier in males than in females. By cause, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) were more likely to impose a burden on the elderly, while acute lymphoblastic leukemia (ALL) showed a greater impact in the younger population. A significant positive correlation was observed between SDI and AAPC in ASIR, while SDI was negatively correlated with AAPCs in both ASDR and age-standardized DALY rate. Smoking remained the most significant risk factor associated with leukemia-related death and DALY, especially in males. Similar deaths and DALYs were caused by smoking and high body mass index (BMI) in females. Future projections through 2030 estimated that ASIR and ASDR will continue to increase, while the DALY rate is predicted to decline. Conclusions. Patterns and trends of leukemia burden are correlated with SDI. The estimated contributions to leukemia deaths indicate that timely measures are needed to reduce smoking and obesity.
SXL is a safe and effective preparation for treatment of ITP, showing an immediate effect which is obviously superior to that of ampeptide elemente with less adverse effect.
Soybean processing waste (SPW) has potential as a sustainable source of phytochemicals and functional foods. A variety of phytochemicals, nutrients, and minerals have been characterized from SPW using various analytical methods. SPW utilization strategies may provide a new way to increase production of bioactive compounds, nutritional supplements, and cosmetic ingredients. SPW has the potential for value-added processing, to improve commercial use, and to lower environmental pollution through proper use. Okara, a byproduct generated during soybean processing of tofu and soy milk, is rich in dietary fiber, isoflavones, and saponins. Isoflavones, an important class of biologically active compounds owing to their multifunctional and therapeutic effects, are extracted from SPW. Further, studies have shown that okara has potential prebiotic and therapeutic value in lowering the risk of noncommunicable diseases. Therefore, in this review, we focus on several extraction methods and pharmacotherapeutic effects of different SPWs. Their effective uses in functional foods, nutraceuticals, and health applications, as biocatalysts, and as value-added resources have been discussed.
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