Diverse functions of TRIB3 in cancers and its potential as a therapeutic target.

Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and successful application of their inhibitors in diseases. Pseudokinases are members of kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating potential for TRIB3 as a therapeutic target.

CARE-radiology statement explanation and elaboration: reporting guideline for radiological case reports.

Despite the increasing number of radiological case reports, the majority lack a standardised methodology of writing and reporting. We therefore develop a reporting guideline for radiological case reports based on the CAse REport (CARE) statement. We established a multidisciplinary group of experts, comprising 40 radiologists, methodologists, journal editors and researchers, to develop a reporting guideline for radiological case reports according to the methodology recommended by the Enhancing the QUAlity and Transparency Of health Research network. The Delphi panel was requested to evaluate the significance of a list of elements for potential inclusion in a guideline for reporting mediation analyses. By reviewing the reporting guidelines and through discussion, we initially drafted 46 potential items. Following a Delphi survey and discussion, the final CARE-radiology checklist is comprised of 38 items in 16 domains. CARE-radiology is a comprehensive reporting guideline for radiological case reports developed using a rigorous methodology. We hope that compliance with CARE-radiology will help in the future to improve the completeness and quality of case reports in radiology.

Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-κB signaling in vivo.

Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.

Periplocin Overcomes Bortezomib Resistance by Suppressing the Growth and Down-Regulation of Cell Adhesion Molecules in Multiple Myeloma.

Multiple myeloma (MM) is an incurable hematological malignant disorder of bone marrow. Patients with MM receive multiple lines of chemotherapeutic treatments which often develop bortezomib (BTZ) resistance and relapse. Therefore, it is crucial to identify an anti-MM agent to overcome the BTZ resistance of MM. In this study, we screened a library of 2370 compounds against MM wild-type (ARP1) and BTZ-resistant type (ARP1-BR) cell lines and found that periplocin (PP) was the most significant anti-MM natural compound. We further investigated the anti-MM effect of PP by using annexin V assay, clonogenic assays, aldefluor assay, and transwell assay. Furthermore, RNA sequencing (RNA-seq) was performed to predict the molecular effects of PP in MM followed by verification through qRT-PCR and Western blot analysis. Moreover, ARP1 and ARP1-BR xenograft mice models of MM were established to confirm the anti-MM effects of PP invivo. The results showed that PP significantly induced apoptosis, inhibited proliferation, suppressed stemness, and reduced the cell migration of MM. The expression of cell adhesion molecules (CAMs) was suppressed upon PP treatment in vitro and in vivo. Overall, our data recommend PP as an anti-MM natural compound with the potential to overcome BTZ resistance and downregulate CAMs in MM.

The Role of CREBBP/EP300 and Its Therapeutic Implications in Hematological Malignancies.

Disordered histone acetylation has emerged as a key mechanism in promoting hematological malignancies. CREB-binding protein (CREBBP) and E1A-binding protein P300 (EP300) are two key acetyltransferases and transcriptional cofactors that regulate gene expression by regulating the acetylation levels of histone proteins and non-histone proteins. CREBBP/EP300 dysregulation and CREBBP/EP300-containing complexes are critical for the initiation, progression, and chemoresistance of hematological malignancies. CREBBP/EP300 also participate in tumor immune responses by regulating the differentiation and function of multiple immune cells. Currently, CREBBP/EP300 are attractive targets for drug development and are increasingly used as favorable tools in preclinical studies of hematological malignancies. In this review, we summarize the role of CREBBP/EP300 in normal hematopoiesis and highlight the pathogenic mechanisms of CREBBP/EP300 in hematological malignancies. Moreover, the research basis and potential future therapeutic implications of related inhibitors were also discussed from several aspects. This review represents an in-depth insight into the physiological and pathological significance of CREBBP/EP300 in hematology.

Acute aortic dissection complicated with hemorrhagic aortopulmonary artery sheath: a review of the literature.

A hemorrhagic aortopulmonary artery sheath (HAPS) is an infrequent and critical complication of aortic dissection (AD), which is caused by a hematoma extending through the ruptured aortic wall into the aortopulmonary artery sheath. The adventitial hematoma might narrow or even occlude the lumen of the pulmonary arteries and extend into the pulmonary interstitium and alveoli. The prompt and accurate recognition of HAPS on computed tomography (CT) is crucial and might assist in the diagnosis of unidentifiable AD. HAPS was manifested as high attenuation areas surrounded the pulmonary arteries without enhancement on CT; even thickened bronchovascular sheath and ground-glass consolidations surrounded bronchovascular distribution, which might be associated with the prognosis. Aggressive and effective surgical treatment is the primary determinant of short-term survival.

Luteolin inhibits the TGF-ß signaling pathway to overcome bortezomib resistance in multiple myeloma.

Multiple myeloma (MM) is an incurable condition and the second most common hematological malignancy. Over the past few years, there has been progress in the treatment of MM, but most patients still relapse. Multiple myeloma stem-like cells (MMSCs) are believed to be the main reason for drug resistance and eventual relapse. Currently, there are not enough therapeutic agents that have been identified for eradication of MMSCs, and thus, identification of the same may alleviate the issue of relapse in patients. In the present study, we showed that luteolin (LUT), a natural compound obtained from different plants, such as vegetables, medicinal herbs, and fruits, effectively inhibits the proliferation of MM cells and overcomes bortezomib (BTZ) resistance in them in vitro and in vivo, mainly by decreasing the proportion of ALDH1+ cells. Furthermore, RNA sequencing after LUT treatment of MM cell lines and an MM xenograft mouse model revealed that the effects of the compound are mediated through inhibition of transforming growth factor-ß signaling. Similarly, we found that LUT also significantly reduced the proportion of ALDH1+ cells in primary CD138+ plasma cells. In addition, LUT could overcome the BTZ treatment-induced increase in the proportion of ALDH1+ cells, and the combination of LUT and BTZ had a synergistic effect against myeloma cells. Collectively, our findings suggested that LUT is a promising agent that manifests MMSCs to overcome BTZ resistance, alone or in combination with BTZ, and thus, is a potential therapeutic drug for the treatment of MM.

[Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine ×100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg·kg-1·d-1, 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC.

A Ferroptosis Molecular Subtype-Related Signature for Predicting Prognosis and Response to Chemotherapy in Patients with Chronic Lymphocytic Leukemia.

Ferroptosis is a type of regulated cell death catalyzed by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder. However, the understanding of ferroptosis in CLL remains largely poor. In this study, we investigated the stratification and prognostic role of ferroptosis-related genes in CLL patients of ICGC cohort. We obtained fourteen genes with prognostic value by screening 110 ferroptosis-related genes (FRGs). Based on the expression profiles of these 14 genes, we classified CLL patients into two clusters. Most of the FRGs were highly expressed in cluster 1, and cluster 1 was associated with better overall survival (OS). Subsequently, we developed an eight-gene signature (TP63, STEAP3, NQO1, ELAVL1, PRKAA1, HELLS, FANCD2, and CDKN2A) by using LASSO analysis. This risk signature divided CLL patients into high- and low-risk groups. We used Cox regression analysis and ROC analysis demonstrated the risk signature was reliable and robust. And we validated the risk model in an external cohort (GSE22762). We also conducted enrichment analysis and genomic mutation analysis. Finally, we explored the potential effect of chemotherapy between the two risk groups. Our study contributed to understanding the role of ferroptosis in CLL and facilitated personalized and precision treatment.

HIF-PH Encoded by EGLN1 Is a Potential Therapeutic Target for Chronic Lymphocytic Leukemia.

Owing to the recent emergence of drug resistance to Bruton's tyrosine kinase inhibitors (BTK) in chronic lymphocytic leukemia (CLL) treatment, it is crucial to identify alternative therapeutic targets. Therefore, we aimed to identify therapeutic options for CLL besides BTK. We identified that HIF1A expression was higher in CLL patients than in controls, which may suggest good prognosis. We used a lentiviral knockdown of EGLN1 (encoding hypoxia-inducible factor prolyl hydroxylase [HIF-PH]) and found that the growth of MEC-1 cells slowed in the knockdown group. Treatment of CLL cell lines MEC-1 and HG3 with the HIF-PH inhibitor molidustat showed that molidustat could induce apoptosis in a concentration-dependent manner in CLL cells and had low cytotoxicity at this concentration. CXCR4, HIF1A, SLC2AI, and VEGF, the downstream molecules of the HIF pathway, were upregulated after molidustat treatment. Western blotting results indicated that molidustat increased HIF1A expression in CLL cell lines and cells from CLL patients, and sequencing/quantitative PCR analysis demonstrated that the ribosome biogenesis pathway was inhibited in MEC-1 cells after molidustat treatment. We further identified synergistic cytotoxicity of molidustat in combination with ibrutinib on the MEC-1 and HG3 cell lines at certain concentrations. Therefore, molidustat is a potential therapeutic option for CLL.

Polyphyllin VII, a novel moesin inhibitor, suppresses cell growth and overcomes bortezomib resistance in multiple myeloma.

Multiple myeloma is a plasma cell malignancy, accounting for approximately 1% of new cancer cases. It is the second most common hematological malignancy. Novel clinical agents such as the proteasome inhibitor-bortezomib, have shown improved survival rates in recent decades. However, multiple myeloma remains incurable, as most patients eventually relapse and become refractory to current treatments. Therefore, there is an urgent need for developing new regimens to overcome the bortezomib resistance. Here, we screened a library of 2370 bioactives and found that polyphyllin VII selectively suppressed multiple myeloma cell growth in vitro and in vivo. We identified moesin, one of the critical regulators of the Wnt/ß-catenin pathway, as a target of polyphyllin VII by drug affinity responsive target stability assay and cellular thermal shift assay. Polyphyllin VII binds to moesin and induces its degradation via the ubiquitin-proteasome pathway, thereby impairing the Wnt/ß-catenin pathway activity and leading to a reduction in the side population cells to overcome bortezomib resistance. Our study identified polyphyllin VII as a promising compound and moesin as a potential diagnostic and therapeutic target for treating multiple myeloma.

Protocol for developing the reporting guidelines for radiological case reports: Case Report for Radiology statement.

Background: In radiology, case reports play an important role in the presentation of a new disease or an unusual form of a common disease using radiological images. Radiology practitioners can refer to the CAse REport (CARE) statement to write and improve the quality of case reports; however, some CARE items are not applicable to the field of radiology. This protocol seeks to describe the methods and processes used to develop CARE extensions for radiology. Methods: We plan to extend the existing CARE guidelines to radiological case reports. We will follow the steps recommended by the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network to develop the CAse Report for Radiology (CARR) statement and checklist for the reporting of case reports. The working group will constitute a multidisciplinary international team of experts, including methodologists, content experts (radiologists and clinicians), journal editors, and possibly consumer representatives. We will discuss and generate a list of initial items based on the CARE statement. Two to three rounds of the Delphi survey will be administered and an online consensus meeting will be held to reach a consensus and develop the final CARR checklist. The full reporting guidelines should be finalized within 1.5 years. Discussion: The annual number of published radiological case reports has increased over the past 20 years; however, the quality of reporting still needs to be improved. Our protocol envisages the process and methodology for the development of the CARR guidelines, which we anticipate will be available soon and will help radiology practitioners. Trial Registration: We have registered the protocol on the EQUATOR network (https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-observational-studies/#CARR).

LncRNA BC200/miR-150-5p/MYB positive feedback loop promotes the malignant proliferation of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a group of heterogeneous hematologic malignancies with a risk of transformation to acute myeloid leukemia. Understanding the molecular mechanisms of the specific roles of long noncoding RNAs (lncRNAs) in MDS would create novel ways to identify diagnostic and therapeutic targets. The lncRNA BC200 is upregulated and acts as an oncogene in various cancers; however, its expression, clinical significance, and roles in MDS remain unclear. Here, we found that BC200 was highly expressed in MDS patients compared with normal individuals. Knockdown of BC200 inhibited MDS cell proliferation, colony formation, and cell cycle progression in vitro and suppressed the growth and invasiveness of MDS cells in vivo. Mechanistic investigations revealed that BC200 functioned as a miRNA sponge to positively regulate the expression of MYB through sponging miR-150-5p and subsequently promoted malignant proliferation of MDS cells. Conversely, we found that BC200 was a direct transcriptional target of MYB, and knockdown of MYB abolished the oncogenic effect of BC200/miR-150-5p. Taken together, our results revealed that the BC200/miR-150-5p/MYB positive feedback loop promoted the proliferation of MDS cells and is expected to be a potential biomarker and therapeutic target in MDS.

Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1.

Despite the establishment of novel therapeutic interventions, multiple myeloma (MM) remains invariably incurable due to development of drug resistance and subsequent relapse, which are attributed to activation of oncogenic pathways such as autophagy. Deubiquitinating enzymes (DUBs) are promising targets to overcome resistance to proteasome inhibitor-based treatment. Ubiquitin-specific protease-12 (USP12) is a DUB with a known prognostic value in several cancers. We found that USP12 protein levels were significantly higher in myeloma patient samples than in non-cancerous human samples. Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy. Mechanistic studies showed that USP12 interacted with, deubiquitylated and stabilized the critical autophagy mediator HMGB1 (high mobility group box-1) protein. Knockdown of USP12 decreased the level of HMGB1 and suppressed HMGB1-mediated autophagy in MM. Furthermore, basal autophagy activity associated with USP12/HMGB1 was elevated in bortezomib (BTZ)-resistant MM cell lines. USP12 depletion, concomitant with a reduced expression of HMGB1, suppressed autophagy and increased the sensitivity of resistant cells to BTZ. Collectively, our findings have identified an important role of the deubiquitylase USP12 in pro-survival autophagy and resultant BTZ resistance in MM by stabilizing HMGB1, suggesting that the USP12/HMGB1 axis might be pursued as a potential diagnostic and therapeutic target in human MM.

Albendazole inhibits NF-κB signaling pathway to overcome tumor stemness and bortezomib resistance in multiple myeloma.

Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1+ MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma.

A Comparison of Lung Ultrasound and Computed Tomography in the Diagnosis of Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background Lung ultrasound (LUS) and computed tomography (CT) can both be used for diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19), but the agreement between LUS and CT is unknown. Purpose to compare the agreement of LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19. Materials and Methods We searched PubMed, Cochrane library, Embase, Chinese Biomedicine Literature, and WHO COVID-19 databases to identify studies that compared LUS with CT in the diagnosis of interstitial pneumonia caused by COVID-19. We calculated the pooled overall, positive and negative percent agreements, diagnostic odds ratio (DOR) and the area under the standard receiver operating curve (SROC) for LUS in the diagnosis of COVID-19 compared with CT. Results We identified 1896 records, of which nine studies involving 531 patients were finally included. The pooled overall, positive and negative percentage agreements of LUS for the diagnosis of interstitial pneumonia caused by COVID-19 compared with CT were 81% (95% confidence interval [CI] 43-99%), 96% (95% CI, 80-99%, I2 = 92.15%) and 80% (95%CI, 60-92%, I2 = 92.85%), respectively. DOR was 37.41 (95% CI, 9.43-148.49, I2 = 63.9%), and the area under the SROC curve was 0.94 (95% CI, 0.92-0.96). The quality of evidence for both specificity and sensitivity was low because of heterogeneity and risk of bias. Conclusion The level of diagnostic agreement between LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19 is high. LUS can be therefore considered as an equally accurate alternative for CT in situations where molecular tests are not available.

Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells.

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.

Visual Quantitative Detection of Glutathione and Cholesterol in Human Blood Based on the Thiol-Ene Click Reaction-Triggered Wettability Change of the Interface.

Herein, we proposed an innovative visual quantitative sensing strategy based on thiol-ene click chemistry and the capillary action principle. A triethoxyvinylsilane (VTEO)- or mercaptopropylsilatrane (MPS)-modified interface was prepared for analyte recognition. Target analyte molecules containing thiol groups or C═C double bonds are coupled to the VTEO- or MPS-modified inner surface of the glass capillary tube via a thiol-ene click reaction, respectively. Then, the molecular recognition events were transformed into the wettability change of the inner wall of the glass capillary. The concentration of the target molecules was quantified by reading the height change of the water column in the capillary tube. As a proof of concept, this strategy was successfully used to build visual quantitative sensors for detecting glutathione and cholesterol. In addition, this strategy showed a good anti-interference ability to complex biological fluids and realized sensitive glutathione (GSH) and cholesterol detection in real human blood samples.

Protein mass spectrometry reveals lycorine exerting anti-multiple-myeloma effect by acting on VDAC2 and causing mitochondrial abnormalities.

OBJECTIVE: Two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry were performed to compare the proteomic alterations of lycorine-treated and control cells to further investigate the anti-multiple myeloma (MM) mechanisms of lycorine. RESULTS: Mass spectrometry results showed that after lycorine treatment of MM cells, 42% of the differentially expressed proteins had subcellular localization, mainly, on mitochondria. Voltage-dependent anion-selective channel protein 2 (VDAC2), the most abundant protein in the outer mitochondrial membrane, was up-regulated after treatment with lycorine and was subsequently verified by western blot analysis. Further studies on mitochondria found that lycorine was able to increase abnormal mitochondria and increase mitochondrial membrane potential. CONCLUSIONS: Lycorine can achieve the effect of resisting multiple myeloma by acting on VDAC2 and causing mitochondrial abnormalities.

Curcumol and FTY720 synergistically induce apoptosis and differentiation in chronic myelomonocytic leukemia via multiple signaling pathways.

Chronic myelomonocytic leukemia (CML) is a myeloid tumor characterized by MDS (myelodysplastic syndrome) and MPN (myeloproliferative neoplasms). Allogeneic hematopoietic stem cell transplantation, chemotherapy, interferon, and targeted therapy are the main treatment methods for CML. Tyrosine kinase inhibitors (TKIs) are also a treatment option, and patients are currently recommended to take these drugs throughout their lives to prevent CML recurrence. Therefore, there is a need to investigate and identify other potential chemotherapy drugs. Currently, research on CML treatment with a single drug has shown little progress. Fingolimod (FTY720), an FDA-approved drug used to treat relapsing multiple sclerosis, has also shown great potential in the treatment of lymphocytic leukemia. In our study, we find that FTY720 and curcumol have a significant inhibitory effect on K562 cells, K562/ADR cells, and CD34+ cells from CML patients. RNAseq data analysis shows that regulation of apoptosis and differentiation pathways are key pathways in this process. Besides, BCR/ABL-Jak2/STAT3 signaling, PI3K/Akt-Jnk signaling, and activation of BH3-only genes are involved in CML inhibition. In a K562 xenograft mouse model, therapy with curcumol and FTY720 led to significant inhibition of tumor growth and induction of apoptosis. To summarize, curcumol and FTY720 synergistically inhibit proliferation involved in differentiation and induce apoptosis in CML cells. Therefore, synergistic treatment with two drugs could be the next choice of treatment for CML.