Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34+ acute myeloid leukemia cell lines and primary sorted CD34+ acute myeloid leukemia cells

<p>Abstract</p> <p>Background</p> <p>Acute myeloid leukemia (AML) is an immunophenotypically heterogenous malignant disease, in which CD34 positivity is associated with poor prognosis. CD34⁺AML cells are 10-15-fold more resistant to daunorubicin (DNR) than CD34^-AML cells. Curcumin is a major component of turmeric that has shown cytotoxic activity in multiple cancers; however, its anti-cancer activity has not been well studied in DNR-insensitive CD34⁺AML cells. The aim of this study was to therefore to explore curcumin-induced cytotoxicity in DNR-insensitive CD34⁺AML cell lines (KG1a, Kasumi-1), DNR-sensitive U937 AML cells, and primary CD34⁺AML bone-marrow-derived cells.</p> <p>Methods</p> <p>Primary human CD34⁺cells were isolated from peripheral blood mononuclear cells or bone marrow mononuclear cells using a CD34 MicroBead kit. The growth inhibitory effects of curcumin were evaluated by MTT and colony-formation assays. Cell cycle distribution was examined by propidium iodide (PI) assay. Apoptosis was analyzed by Wright-Giemsa, Hoechst 33342 and Annexin-V/PI staining assays. The change in mitochondrial membrane potential (MMP) was examined by JC-1 staining and flow cytometry. Expression of apoptosis-related proteins was determined by reverse transcription-polymerase chain reaction and Western blotting. Short interfering RNA (siRNA) against <it>Bcl-2 </it>was used in CD34⁺KG1a and Kasumi-1 cells incubated with/without DNR.</p> <p>Results</p> <p>Curcumin inhibited proliferation and induced apoptosis and G1/S arrest in both DNR-insensitive KG1a, Kasumi-1 and DNR-sensitive U937 cells. Curcumin-induced apoptosis was associated with reduced expression of both Bcl-2 mRNA and protein, subsequent loss of MMP, and activation of caspase-3 followed by PARP degradation. Curcumin synergistically enhanced the cytotoxic effect of DNR in DNR-insensitive KG1a and Kasumi-1 cells, consistent with decreased Bcl-2 expression. Accordingly, siRNA against <it>Bcl-2 </it>increased the susceptibility of KG1a and Kasumi-1 cells to DNR-induced apoptosis. More importantly, curcumin suppressed Bcl-2 expression, selectively inhibited proliferation and synergistically enhanced the cytotoxicity of DNR in primary CD34⁺AML cells, while showing limited lethality in normal CD34⁺hematopoietic progenitors.</p> <p>Conclusion</p> <p>Curcumin down-regulates Bcl-2 and induces apoptosis in DNR-insensitive CD34⁺AML cell lines and primary CD34⁺AML cells.</p

Serological surveillance of GI norovirus reveals persistence of blockade antibody in a Jidong community-based prospective cohort, 2014–2018

IntroductionHerd immunity against norovirus (NoV) is poorly understood in terms of its serological properties and vaccine designs. The precise neutralizing serological features of genotype I (GI) NoV have not been studied.MethodsTo expand insights on vaccine design and herd immunity of NoVs, seroprevalence and seroincidence of NoV genotypes GI.2, GI.3, and GI.9 were determined using blockade antibodies based on a 5-year longitudinal serosurveillance among 449 residents in Jidong community.ResultsCorrelation between human histo-blood group antigens (HBGAs) and GI NoV, and dynamic and persistency of antibodies were also analyzed. Seroprevalence of GI.2, GI.3, and GI.9 NoV were 15.1%–18.0%, 35.0%–38.8%, and 17.6%–22.0%; seroincidences were 10.0, 21.0, and 11.0 per 100.0 person-year from 2014 to 2018, respectively. Blockade antibodies positive to GI.2 and GI.3 NoV were significantly associated with HBGA phenotypes, including blood types A, B (excluding GI.3), and O+; Lewis phenotypes Leb+/Ley+ and Lea+b+/Lex+y+; and secretors. The overall decay rate of anti-GI.2 antibody was -5.9%/year (95% CI: -7.1% to -4.8%/year), which was significantly faster than that of GI.3 [-3.6%/year (95% CI: -4.6% to -2.6%/year)] and GI.9 strains [-4.0%/year (95% CI: -4.7% to -3.3%/year)]. The duration of anti-GI.2, GI.3, and GI.9 NoV antibodies estimated by generalized linear model (GLM) was approximately 2.3, 4.2, and 4.8 years, respectively.DiscussionIn conclusion, enhanced community surveillance of GI NoV is needed, and even one-shot vaccine may provide coast-efficient health benefits against GI NoV infection

Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health

The fruits of Xanthium sibiricum Patr: A review on phytochemistry, pharmacological activities, and toxicity

In recent years, drug development and research have gradually shifted from chemical synthesis to biopharmaceutical and natural drugs. Natural medicines, such as traditional Chinese medicine, have been among the first studied because of their long medicinal history, simplicity, and the relatively low cost of research. Among them, Xanthii Fructus (XF) is famous for the treatment of sinusitis. In this article, the achievements of research on XF from 1953 to 2020 are systematically reviewed, focusing on the aspects of chemical constituents, pharmacological effects, clinical applications, toxicity and side effects, and processing methods. To date, there have been significant advances in both the phytochemistry and pharmacology of XF. Some traditional uses have been validated and clarified in modern pharmacological studies. However, its mechanism of action in the treatment of allergic diseases has not been satisfactorily explained. Further in vitro and in vivo studies are required to rationally develop new drugs and to elucidate the therapeutic potential of XF. A comprehensive evaluation of XF and an understanding of network pharmacology are also needed. © 2020 World Journal of Traditional Chinese Medicine | Published by Wolters Kluwer ‑ Medknow

Devil's tools: SARS-CoV-2 antagonists against innate immunity

The unprecedented Coronavirus pandemic of 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Like other coronaviruses, to establish its infection, SARS-CoV-2 is required to overcome the innate interferon (IFN) response, which is the first line of host defense. SARS-CoV-2 has also developed complex antagonism approaches involving almost all its encoding viral proteins. Here, we summarize our current understanding of these different viral factors and their roles in suppressing IFN responses. Some of them are conserved IFN evasion strategies used by SARS-CoV; others are novel countermeasures only employed by SARS-CoV-2. The filling of gaps in understanding these underlying mechanisms will provide rationale guidance for applying IFN treatment against SARS-CoV-2 infection

Modeling the effects of cigarette smoke extract on influenza B virus infections in mice

Influenza B virus (IBV) is a major respiratory viral pathogen. Due to a lack of pandemic potential for IBV, there is a lag in research on IBV pathology and immunological responses compared to IAV. Therefore, the impact of various lifestyle and environmental factors on IBV infections, such as cigarette smoking (CS), remains elusive. Despite the increased risk and severity of IAV infections with CS, limited information exists on the impact of CS on IBV infections due to the absence of suitable animal models. To this end, we developed an animal model system by pre-treating mice for two weeks with cigarette smoke extract (CSE), then infected them with IBV and monitored the resulting pathological, immunological, and virological effects. Our results reveal that the CSE treatment decreased IBV specific IgG levels yet did not change viral replication in the upper airway/the lung, and weight recovery post infection. However, higher concentrations of CSE did result in higher mortality post infection. Together, this suggests that CS induced inflammation coupled with IBV infection resulted in exacerbated disease outcome

The VAD Scheme versus Thalidomide plus VAD for Reduction of Vascular Endothelial Growth Factor in Multiple Myeloma: A Meta-Analysis

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52–518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21–1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28− -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60–-39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08–377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD

Impact of Protein Nitration on Influenza Virus Infectivity and Immunogenicity

Influenza viruses are deadly respiratory pathogens of special importance due to their long history of global pandemics. During influenza virus infections, the host responds by producing interferons, which activate interferon-stimulated genes (ISGs) inside target cells. One of these ISGs is inducible nitric oxide synthase (iNOS). iNOS produces nitric oxide (NO) from arginine and molecular oxygen inside the cell. NO can react with superoxide radicals to form reactive nitrogen species, principally peroxynitrite. While much work has been done studying the many roles of nitric oxide in influenza virus infections, the direct effect of peroxynitrite on influenza virus proteins has not been determined. Manipulations of NO, either by knocking out iNOS or chemically inhibiting NO, produced no change in virus titers in mouse models of influenza infection. However, peroxynitrite has a known antimicrobial effect on various bacteria and parasites, and the reason for its lack of antimicrobial effect on influenza virus titers in vivo remains unclear. Therefore, we wished to test the direct effect of nitration of influenza virus proteins. We examined the impact of nitration on virus infectivity, replication, and immunogenicity. We observed that the nitration of influenza A virus proteins decreased virus infectivity and replication ex vivo. We also determined that the nitration of influenza virus hemagglutinin protein can reduce antibody responses to native virus protein. However, our study also suggests that nitration of influenza virus proteins in vivo is likely not extensive enough to inhibit virus functions substantially. These findings will help clarify the role of peroxynitrite during influenza virus infections. IMPORTANCE Nitric oxide and peroxynitrite produced during microbial infections have diverse and seemingly paradoxical functions. While nitration of lung tissue during influenza virus infection has been observed in both mice and humans, the direct effect of protein nitration on influenza viruses has remained elusive. We addressed the impact of nitration of influenza virus proteins on virus infectivity, replication, and immunogenicity. We observed that ex vivo nitration of influenza virus proteins reduced virus infectivity and immunogenicity. However, we did not detect nitration of influenza virus hemagglutinin protein in vivo. These results contribute to our understanding of the roles of nitric oxide and peroxynitrite in influenza virus infections

Epidemiology and Clinical Presentations of Respiratory Syncytial Virus Subgroups A and B Detected with Multiplex Real-Time PCR.

Respiratory syncytial virus (RSV) is one of the most important pathogenic infections of children and requires in-depth research worldwide, and especially in developing countries. We used a novel multiplex real-time PCR to test 5483 patients (≤ 14 years old) hospitalized with respiratory illness in Guangzhou, China, over a 3-year period. Of these patients, 729 were positive for RSV-A (51.2%, 373/729) or RSV-B (48.8%, 356/729), but none was infected with both viruses. Two seasonal peaks in total RSV were detected at the changes from winter to spring and from summer to autumn. RSV-B was dominant in 2013 and RSV-A in 2015, whereas RSV-A and RSV-B cocirculated in 2014. The clinical presentations of 645 RSV-positive patients were analyzed. Bronchiolitis, dyspnea, coryza, vomiting, poor appetite, and diarrhea occurred more frequently in RSV-A-positive than RSV-B-positive patients, whereas chill, headache, myalgia, debility, and rash etc. were more frequent in RSV-B-positive than RSV-A-positive patients, suggesting specific clinical characteristics for RSV-A and RSV-B. Coinfectons with other pathogens were common and diverse. Bronchiolitis, fever (≥ 38°C), and poor appetite were more frequent in patients with single RSV infections than in coinfected patients, suggesting the key pathogenic activity of RSV. Analysis of the relationships between the comparative viral load and clinical presentations showed significant differences in bronchiolitis, fever (≥ 38°C), and rash etc. among patients with different viral loads. This study provides a novel rapid method for detecting RSV subgroups, and provides new insights into the epidemiology and clinical implications of RSV