Diagnostic roles of neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein, and cancer antigen 125 for ovarian cancer.

OBJECTIVE: To compare the diagnostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP) level, and cancer antigen 125 (CA125) level for ovarian cancer (OC). METHODS: Data of 72 patients with OC, 50 patients with benign ovarian disease, and 46 healthy controls were retrospectively analyzed, and receiver operating characteristic analysis was performed. RESULTS: The platelet count was higher in patients with a tumor diameter of ≥10 vs. <10 cm. The absolute lymphocyte count was significantly higher in patients with stage I/II OC than in those with multiple and stage III/IV OC. The absolute monocyte count, NLR, MLR, and CA125 were significantly higher in patients with multiple and stage III/IV OC than in those with single and stage I/II OC. The NLR, PLR, MLR, fibrinogen, D-dimer, CRP, and CA125 were useful for distinguishing between the OC and healthy control groups. CONCLUSIONS: Our analysis showed that the following combinations have practical diagnostic value in OC: NLR + PLR + MLR + CA125, NLR + PLR + MLR + CA125 + CRP, NLR + MLR +PLR + CA125 + CRP + fibrinogen, and NLR + MLR + PLR + CA125 + CRP + fibrinogen + D-dimer.

Novel cell subtypes of SPP1 + S100P+, MS4A1-SPP1 + S100P+ were key subpopulations in intrahepatic cholangiocarcinoma.

BACKGROUND: In this study, we integrated single-cell RNA sequencing (scRNA-seq) data to investigate cell heterogeneity and utilized MSigDB and CIBERSORTx to explore the pathways of major cell types and the relationships between different cell subtypes. Subsequently, we explored the correlation of cell subtypes with survival and used Gene Set Enrichment Analysis (GSEA) analyses to assess the pathways associated with the infiltration of specific cell subtypes. Finally, multiplex immunohistochemistry in tissue microarray cohort were performed to validate differences in protein level and their correlation with survival. RESULTS: iCCA presented a unique immune ecosystem, with increased proportions of Epi (epithelial)-SPP1-2, Epi-S100P-1, Epi-DN (double negative for SPP1 and S100P expression)-1, Epi-DN-2, Epi-DP (double positive for SPP1 and S100P expression)-1, Plasma B-3, Plasma B-2, B-HSPA1A-1, B-HSPA1A-2 cells, and decreased proportions of B-MS4A1. High level of Epi-DN-2, Epi-SPP1-1, Epi-SPP1-2, B-MS4A1, and low level of Epi-DB-1, Epi-S100P-1, and Epi-S100P-2 was significantly associated with longer overall survival (OS), and high level of B-MS4A1_Low_Epi-DN-2_Low was associated with the shortest OS. Moreover, the results of MsigDB and GSEA suggest that bile acid metabolism is a crucial process in iCCA. Finally, we found that S100P+, SPP1+, SPP1 + S100P+, and MS4A1-SPP1 + S100P+ were highly expressed, whereas MS4A1 was lowly expressed in iCCA, and patients with high level of S100P+, SPP1 + S100P+, and MS4A1-SPP1 + S100P+ exhibited shorter survival. CONCLUSIONS: We identified the cell heterogeneity of iCCA, found that iCCA is a unique immune ecosystem with many cell subtypes, and showed that the novel cell subtypes of SPP1 + S100P+ and MS4A1-SPP1 + S100P+ were key subpopulations in iCCA.

Rhizosphere soil properties of waxy sorghum under different row ratio configurations in waxy sorghum-soybean intercropping systems.

To overcome the continuous planting obstacle and promote the sustainable production of waxy sorghum, a two-years field experiment was performed to determine the responses of waxy sorghum rhizosphere soil properties to different row ratio configurations in waxy sorghum-soybean intercropping systems. The treatments included five row ratio configurations, which were two rows of waxy sorghum intercropped with one row of soybean (2W1S), two rows of waxy sorghum intercropped with two rows of soybean (2W2S), three rows of waxy sorghum intercropped with one row of soybean (3W1S), three rows of waxy sorghum intercropped with two rows of soybean (3W2S), and three rows of waxy sorghum intercropped with three rows of soybean (3W3S), and sole cropping waxy sorghum (SW) was used as control. The nutrients, enzyme activities, and microbes of waxy sorghum rhizosphere soil were investigated at the jointing, anthesis, and maturity stages. Results showed that rhizosphere soil properties of waxy sorghum were significantly affected by row ratio configurations of waxy sorghum intercropped soybean. Among all treatments, the performances of rhizosphere soil nutrients contents, enzymes activities, and microbes contents were 2W1S > 3W1S > 3W2S > 3W3S > 2W2S > SW. Compared to SW treatment, the 2W1S treatment increased the organic matter, total N, total P, total K, gram-negative bacteria phospholipid fatty acids (PLFAs), and gram-positive bacteria PLFAs contents and catalase, polyphenol oxidase, and urease activities by 20.86%-25.67%, 34.33%-70.05%, 23.98%-33.83%, 44.12%-81.86%, 74.87%-194.32%, 81.59-136.59%, 91.44%-114.07%, 85.35%-146.91%, and 36.32%-63.94%, respectively. Likewise, the available N, available P, available K, total PLFAs, fungus PLFAs, actinomycetes PLFAs, and bacteria PLFAs contents under the 2W1S treatment were 1.53-2.41, 1.32-1.89, 1.82-2.05, 1.96-2.91, 3.59-4.44, 9.11-12.56, and 1.81-2.71 times than those of SW treatment, respectively. Further, the determining factors of soil microbes were total K, catalase, and polyphenol oxidase for total microbes, bacteria, and gram-negative bacteria, total P and available K for fungus, available N, available K, and polyphenol oxidase for actinomycetes, and total K and polyphenol oxidase for gram-positive bacteria. In conclusion, the 2W1S treatment was the optimal row ratio configuration of waxy sorghum intercropped with soybean, which can improve the rhizosphere soil quality and promote the sustainable production of waxy sorghum.

Identification of Protein Quality Markers in Toad Venom from Bufo gargarizans.

Toad venom is a traditional Chinese medicine with high medicinal value. The existing quality evaluation standards of toad venom have obvious limitations because of the lack of research on proteins. Thus, it is necessary to screen suitable quality markers and establish appropriate quality evaluation methods for toad venom proteins to guarantee their safety and efficacy in clinical applications. SDS-PAGE, HPLC, and cytotoxicity assays were used to analyze differences in protein components of toad venom from different areas. Functional proteins were screened as potential quality markers by proteomic and bioinformatic analyses. The protein components and small molecular components of toad venom were not correlated in content. Additionally, the protein component had strong cytotoxicity. Proteomics analysis showed that 13 antimicrobial proteins, four anti-inflammatory and analgesic proteins, and 20 antitumor proteins were differentially expressed extracellular proteins. A candidate list of functional proteins was coded as potential quality markers. Moreover, Lysozyme C-1, which has antimicrobial activity, and Neuropeptide B (NPB), which has anti-inflammatory and analgesic activity, were identified as potential quality markers for toad venom proteins. Quality markers can be used as the basis of quality studies of toad venom proteins and help to construct and improve safe, scientific, and comprehensive quality evaluation methods.

The Heterogeneity of Tumour-Associated Macrophages Contributes to the Recurrence and Outcomes of Glioblastoma Patients.

Cellular heterogeneity and immune cell molecular phenotypes may be involved in the malignant progression of glioblastoma (GBM). In this study, we aimed to know whether the heterogeneity of tumour-associated macrophages contributes to the recurrence and outcomes of glioblastoma patients. Single-cell RNA sequencing (scRNA-Seq) data were used to assess the heterogeneity of CD45 + immune cells in recurrent GBM and analyse differentially expressed genes (DEGs) in master cells. Then, a prognostic signature based on the identified DEGs was established and validated, the correlation between risk score and tumour microenvironment (TME) was explored. The correlation between immune infiltration and LGMN, an important DEG in GBM tumour-associated macrophages (TAMs) was illuminated, using integrated bioinformatics analyses. Finally, immunohistochemistry and multiplex immunohistochemistry (mIHC) were used to analyse the expression of LGMN in GBM tissues from our hospital. scRNA-Seq analysis showed that the heterogeneity of recurrent GBM mainly comes from TAMs, which can be divided into 8 cell subclusters. Among these subclusters, TAM1 (markers: CXCL10, ADORA3), TAM3 (markers: MRC1, CFP), TAM4 (markers: GPNMB, PLTP), and TAM5 (markers: CCL4, IRAK2) were specifically present in recurrent GBM. After 342 DEGs in TAMs were identified, a prognostic signature was established based on 13 TAM-associated DEGs, and this signature could serve as an excellent prognostic predictor for patients with GBM. LGMN, one of 13 TAM-associated DEGs, was an important gene in lysosome pathway, we found that macrophage infiltration levels were higher after LGMN upregulation. GBM tissues from our hospital were collected for histopathologic validation, then LGMN was co-expressed with CD68, which is associated with the immune regulation of GBM. In conclusion, cell heterogeneity of TAMs is important for recurrent GBM, a prognostic signature based on 13 TAM-related DEGs can predict the survival outcome of GBM patients. An important DEG, LGMN may regulate the immune cell infiltration of GBM.

Associations between dietary fiber intake and cardiovascular risk factors: An umbrella review of meta-analyses of randomized controlled trials.

Although several meta-analyses have revealed the beneficial effects of dietary fiber intake on human health, some have reported inconsistent findings. The purpose of this work was to perform an umbrella meta-analysis to evaluate the relevant evidence and elucidate the effect of dietary fiber intake on glycemic control, lipid profiles, systematic inflammation, and blood pressure. Eligible studies were searched in several electronic databases, including Web of Science, PubMed, Scopus, and the Cochrane Library, up to March 2022. A total of 52 meta-analyses involving 47,197 subjects were identified to assess the pooled effect size. Overall, higher dietary fiber intake was significantly associated with reductions in parameters involving glycemic control, including fasting plasma glucose (ES = -0.55, 95% CI: -0.73, -0.38, P < 0.001), fasting plasma insulin (ES = -1.22, 95% CI: -1.63, -0.82, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (ES = -0.43, 95% CI: -0.60, -0.27, P < 0.001), and glycosylated hemoglobin (HbA1c) (ES = -0.38, 95% CI: -0.50, -0.26, P < 0.001). In terms of lipid profiles, higher dietary fiber intake was associated with significant reductions in the serum level of total cholesterol (ES = -0.28, 95% CI: -0.39, -0.16, P < 0.001) and low-density lipoprotein cholesterol (ES = -0.25, 95% CI: -0.34, -0.16, P < 0.001), but not triglycerides (ES = -0.001, 95% CI: -0.006, 0.004, P = 0.759) and high-density lipoprotein cholesterol (ES = -0.002, 95% CI: -0.004, 0.000, P = 0.087). Higher dietary fiber intake was also significantly associated with improved tumor necrosis factor-alpha serum levels (ES = -0.78, 95% CI: -1.39, -0.16, P = 0.013), while no significant effect was observed for C-reactive protein (ES = -0.14, 95% CI: -0.33, 0.05, P = 0.156). Finally, blood pressure was also significantly improved following higher dietary fiber intake (systolic blood pressure: ES = -1.72, 95% CI: -2.13, -1.30, P < 0.001; diastolic blood pressure: ES = -0.67, 95% CI: -0.96, -0.37, P < 0.001). Subgroup analysis revealed that the study population and type of dietary fiber could be partial sources of heterogeneity. In conclusion, the present umbrella meta-analysis provides evidence for the role of dietary fiber supplementation in the improvement of established cardiovascular risk factors.

A Comprehensive Evaluation of Effects on Water-Level Deficits on Tomato Polyphenol Composition, Nutritional Quality and Antioxidant Capacity.

Tomatoes have high nutritional value and abundant bioactive compounds. Moderate water deficit irrigation alters metabolic levels of fruits, improving composition and quality. We investigated the effects of water deficit (T1, T2, T3, and T4) treatments and adequate irrigation (CK) on tomato polyphenol composition, antioxidant capacity, and nutritional quality. Compared with CK, the total flavonoid content increased by 33.66% and 44.73% in T1 and T2, and total phenols increased by 57.64%, 72.22%, and 55.78% in T1, T2, and T3, respectively. The T2 treatment significantly enhanced antioxidant' capacities (ABTS, HSRA, FRAP, and DPPH). There were multiple groups of significant or extremely significant positive correlations between polyphenol components and antioxidant activity. For polyphenols and antioxidant capacity, the classification models divided the treatments: CK and T4 and T1−T3. The contents of soluble solids, soluble protein, vitamin C, and soluble sugar of the treatment groups were higher than those of CK. The soluble sugar positively correlated with sugar−acid ratios. In the PCA-based model, T3 in the first quadrant indicated the best treatment in terms of nutritional quality. Overall, comprehensive rankings using principal component analysis (PCA) revealed T2 > T1 > T3 > T4 > CK. Therefore, the T2 treatment is a suitable for improving quality and antioxidant capacity. This study provides novel insights into improving water-use efficiency and quality in the context of water scarcity worldwide.

Treatment patterns, effectiveness, and patient-reported outcomes of palbociclib therapy in Chinese patients with advanced breast cancer: A multicenter ambispective real-world study.

BACKGROUND: Palbociclib was the only available cyclin-dependent kinase 4/6 inhibitor in China until very recently, and its effect has not been systemically evaluated among Chinese patients. This study aims to assess the efficacy, safety and patient-reported outcomes (PROs) of palbociclib plus endocrine therapy (ET) in real-world China. METHODS: An ambispective cohort study was conducted on patients with advanced HR+HER2- breast cancer who received palbociclib between July 2018, and November 2020 and were enrolled from 12 hospitals. Treatment patterns, survival outcomes, and safety events were documented, and PROs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items [EORTC QLQ-C30] and EuroQoL 5 dimensions [EQ-5D]) were analyzed. The Kaplan-Meier method was used to visualize and estimate the median progression-free survival (mPFS). Log-rank tests, Cox regressions, t tests, and chi-square tests were performed for comparison. RESULTS: A total of 190 patients (median follow-up of 18.0 months) were enrolled. Palbociclib was mostly combined with aromatase inhibitors (66.3%), fulvestrant (32.6%), and tamoxifen (1.1%). The mPFS values were 21.0, 14.0, and 7.0 months with palbociclib administered in first- (n = 83), second- (n = 41) and subsequent-line settings (n = 66), respectively. Endocrine sensitivity was significantly associated with patient prognosis (mPFS: 23.0, 12.0, and 6.0 months for endocrine naïve, acquired, and primary resistant patients, respectively, p < 0.01). The outcome was worse for patients who failed to meet the inclusion criteria of PALOMA-3 than for those who met the criteria (later-line: 6.0 months vs. 9.0 months). The most common adverse events (AEs) were neutropenia (74.2%; grade 3/4: 30.0%), fatigue (48.4%), anemia (32.6%), and thrombocytopenia (22.1%). PRO data suggested that palbociclib plus ET significantly improved cognitive and emotional function, pain symptoms, and overall quality of life. CONCLUSIONS: Palbociclib is effective for front-line use and for treating endocrine-sensitive patients in real-world China and is generally well tolerated. The prevalence of AEs in the Chinese population is different from that reported in the PALOMA-2/3 trials.

Integrative genomic analysis of N6-methyladenosine-single nucleotide polymorphisms (m6A-SNPs) associated with breast cancer.

Due to the important role of N6-methyladenosine (m6A) in breast cancer, single nucleotide polymorphisms (SNPs) in genes with m6A modification may also be involved in breast cancer pathogenesis. In this study, we used a public genome-wide association study dataset to identify m6A-SNPs associated with breast cancer and to further explore their potential functions. We found 113 m6A-SNPs associated with breast cancer that reached the genome-wide suggestive threshold (5.0E-05), and 86 m6A-SNPs had eQTL signals. Only six genes were differentially expressed between controls and breast cancer cases in GEO datasets (GSE15852, GSE115144, and GSE109169), and the SNPs rs4829 and rs9610915 were located next to the m6A modification sites in the 3'UTRs of TOM1L1 and MAFF, respectively. In addition, we found that polyadenylate-binding protein cytoplasmic 1 might have a potential interaction with rs4829 (TOM1L1) and rs9610915 (MAFF). In summary, these findings indicated that the SNPs rs4829 and rs9610915 are potentially associated with breast cancer because they had eQTL signals, altered gene expression, and were located next to the m6A modification sites in the 3'UTRs of their coding genes. However, further studies are still needed to clarify how genetic variation affects the epigenetic modification, m6A, and its subsequent functions in the pathogenesis of breast cancer.

Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer.

BACKGROUND: Aberrant DNA methylation is significantly associated with breast cancer. METHODS: In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. RESULTS: In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994-1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976-1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. CONCLUSIONS: Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

CYP2J2/EET reduces vulnerability to atrial fibrillation in chronic pressure overload mice.

Growing evidence has well established the protective effects of CYP2J2/EET on the cardiovascular system. The aim of the present study was to determine whether CYP2J2/EET has a preventive effect on atrial fibrillation (AF) and to investigate the underlying mechanisms. Wild-type mice were injected with or without AAV9-CYP2J2 before abdominal aortic constriction (AAC) operation. After 8 weeks, compared with wild-type mice, AAC mice display higher AF inducibility and longer AF durations, which were remarkably attenuated with AAV9-CYP2J2. Also, AAV9-CYP2J2 reduced atrial fibrosis area and the deposit of collagen-I/III in AAC mice, accompanied by the blockade of TGF-ß/Smad-2/3 signalling pathways, as well as the recovery in Smad-7 expression. In vitro, isolated atrial fibroblasts were administrated with TGF-ß1, EET, EEZE, GW9662, SiRNA Smad-7 and pre-MiR-21, and EET was demonstrated to restrain the differentiation of atrial fibroblasts largely dependent on Smad-7, due to the inhibition of EET on MiR-21. In addition, increased inflammatory cytokines, as well as activated NF-κB pathways induced by AAC surgery, were also significantly blunted by AAV9-CYP2J2 treatment. These effects of CYP2J2/EET were partially blocked by GW9662, the antagonist of PPAR-γ. In conclusion, this study revealed that CYP2J2/EET ameliorates atrial fibrosis through modulating atrial fibroblasts activation by disinhibition of MiR-21 on Smad-7, and attenuates atrial inflammatory response by repressing NF-κB pathways, reducing the vulnerability to AF, and CYP2J2/EET exerts its role at least partially through PPAR-γ activation. Our findings might provide a novel upstream therapeutic strategy for AF.

Epoxyeicosatrienoic acid prevents maladaptive remodeling in pressure overload by targeting calcineurin/NFAT and Smad-7.

BACKGROUND: Emerging evidence demonstrates that epoxyeicosatrienoic acids (EETs) as important active eicosanoids that regulate cardiovascular homeostasis, but the mechanisms underlying its favorable anti-hypertrophic benefits in overpressure model remain obscure. METHODS AND RESULTS: Four weeks after transverse aortic constriction (TAC), TAC mice developed maladaptive cardiac hypertrophy and consequent cardiac failure. Conversely, a cardiotropic adeno-associated viral vector (AAV9) encoding CYP2J2 prevented transverse aortic constriction-induced cardiac hypertrophy with preserved ejection fraction. EET also conferred protection against phenylephrine-induced hypertrophy in H9c2 cardiomyoblasts. Further investigations indicate CYP2J2/EET exerts protection against cardiac hypertrophy through opposing the increase of intracellular Ca2+ level and Ca2+-mediated calcineurin/NFATc3 signaling. Meanwhile, extended myocardial fibrosis in TAC mice was also effectively abolished with the administration of AAV9-2J2. Intriguingly, TAC mice display activated TGF-ß/Samd-3 signaling with decreased Smad-7 expression, whereas AAV9-2J2 attenuated the phosphorylation of Smad-3 without altering TGF-ß expression, whilst preservation of Smad-7. Subsequently, the differentiation of cardiac fibroblasts into myofibroblasts in the presence of TGF-ß1 stimulation was significantly disrupted with EET treatment, accompanied by declined Smad-3 activation and collagen production, whereas inhibition of Smad-7 with SiRNA Smad-7 substantially abrogated these effects of EET on cardiac fibroblasts. CONCLUSIONS: EET has synergistic actions on cardiomyocytes and cardiac fibroblasts, preventing cardiac hypertrophy through inhibition of Ca2+-mediated calcineurin/NFATc3 signaling cascades, and ameliorating myocardial fibrosis dependent on Smad-7. This work further extends the potential mechanisms of EET, providing a novel therapeutic approach for the treatment of pathological remodeling and heart failure.

Hydroxychloroquine potentiates the anti-cancer effect of bevacizumab on glioblastoma via the inhibition of autophagy.

Bevacizumab (BEV) is widely used for the treatment of patients with recurrent glioblastoma (GBM), but recent evidence demonstrated that BEV induced cytoprotective autophagy, which allows tumor cells to survive. Hydroxychloroquine (HCQ) inhibits lysosomal acidification and blocks autophagy via influencing autophagosome fusion and degradation. HCQ is often used to enhance the efficacy of chemoradiotherapy. However, whether HCQ sensitizes GBM cells to BEV and the molecular mechanism of this effect are not clear. We showed that high concentrations of BEV increased the LC3-II/LC3-I ratio and caused the degradation of Beclin1 in the LN18 and LN229 cell lines, indicating that high concentrations of BEV induced the autophagy of the LN18 and LN229 cells. However, BEV (100 µg/ml) did not influence the autophagy of the LN18 and LN229 cells, and HCQ at less than 5 µg/ml significantly accumulated LC3B-II and p62 proteins and blocked the autophagy process. Importantly, we found that HCQ (5 µg/ml) potentiated the anti-cancer effect of BEV (100 µg/ml). Therefore, HCQ is a novel strategy that may augment the efficacy of BEV for GBM via the inhibition of autophagy.

Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer.

Gastric cancer is an important cancer type worldwide, the anti­angiogenic agent BC001 can target the vascular endothelial growth factor receptor 2 (VEGFR2), and significantly suppresses the growth of gastric cancer BGC823 cells in vitro and in vivo. However, numerous results indicated that antiangiogenic drugs could induce autophagy, and the inhibition of autophagy enhanced the anticancer effects of antiangiogenic agents. In the present study, hydroxychloroquine (HCQ), an inhibitor of autophagy, enhanced the antiproliferative and proapoptotic effects of BC001 in vitro. Furthermore, HCQ enhanced the antitumor effects of BC001 on BGC823 xenograft tumors in vivo. Of note, BC001 neither induced nor inhibited autophagy. RNA­sequencing results revealed that HCQ regulated autophagy or lysosomal­associated genes, such as tumor protein p53­inducible nuclear protein 1, interleukin (IL)1B, tumor necrosis factor (TNF), Mediterranean fever, ubiquitin specific peptidase 36, IL6, neuraminidase (NEU)1, ATP­binding cassette subfamily A member 1, proprotein convertase subtilisin/kexin type 9, myelin basic protein and NEU3. Importantly, HCQ was determined to affect multiple pathways, including 'negative regulation of endothelial cell proliferation', 'blood vessel remodeling', 'cell surface receptor signaling pathways' and 'notch receptor processing' associated with 'signal transduction', 'cancers' and 'immune system', through regulating C­X­C motif chemokine ligand 8, TNF, IL6, intercellular adhesion molecule 1 and FOS genes. In summary, HCQ was proposed to enhance the anticancer effects of BC001 in gastric cancer via complex mechanisms.

Identification of angiogenesis-inhibiting peptides from Chan Su.

Chan Su is a traditional medicine prepared from toxic secretions from the auricular and skin glands of Chinese toads. Previous studies show that active components in Chan Su can inhibit the proliferation of tumor cells. To study the effect of Chan Su peptides on angiogenesis, fresh Chan Su was collected and its component peptides were isolated by an extraction and precipitation method. A high-performance liquid chromatography (HPLC) fingerprint of the Chan Su component peptides revealed that there were more than 18 peptide component peaks. We demonstrate that Chan Su peptides inhibit angiogenesis in vitro by inhibiting human umbilical vein endothelial cell (HUVEC) proliferation and tube formation in a dose-dependent manner. Western blots indicated that Chan Su peptides inhibited the protein expression of VEGF165 and Ras, leading us to conclude that Chan Su peptide components exert anti-angiogenic effects by suppressing the VEGF165-VEGFR2-Ras signalling pathway. Finally, we identified the partial amino acid sequences of seven Chan Su peptides using the shotgun proteomics method.

Semiconducting polymer-based nanoparticles with strong absorbance in NIR-II window for in vivo photothermal therapy and photoacoustic imaging.

Near-infrared (NIR) light-induced photothermal therapy (PTT) has attracted much interest in recent years. In the NIR region, tissue penetration ability of the second biological near-infrared window (1000-1350 nm) is recognized to be stronger than that of the first window (650-950 nm). However, NIR light absorbers in the second NIR region (NIR-II) have been scant even though various NIR light absorbers in the first NIR region (NIR-I) have been widely explored. In this work, a thieno-isoindigo derivative-based semiconducting polymer, PBTPBF-BT, were formulated into PEGylated nanoparticles. The obtained nanoparticle NPPBTPBF-BT exhibited strong absorption in NIR-II region, inherent high photothermal conversion efficacy, and excellent photostability. The in vitro and in vivo PTT study employing 1064 nm laser in NIR-II window revealed that NPPBTPBF-BT could efficiently ablate tumor cell at a power density of 0.42 W/cm2 (the skin tolerance threshold value). Moreover, NPPBTPBF-BT with excellent photostability exhibited enhanced photoacoustic (PA) imaging of tumor in living mice, suggesting the great probability of using NPPBTPBF-BT for in vivo PA imaging-guided PTT in the NIR-II window.

Investigating the Effect of Chemical Structure of Semiconducting Polymer Nanoparticle on Photothermal Therapy and Photoacoustic Imaging.

The donor-acceptor semiconducting polymers (SPs) have robust absorbance in near-infrared (NIR) region, great photostability, high photothermal conversion efficiency, and good biocompatibility. Thus, the SPs exhibit great potentials for photothermal therapy (PTT) and photoacoustic imaging (PAI). However, poor understanding of the underlying mechanisms and the correlation between the SP polymer chemical structures and their performances of PTT and PAI have significantly hindered their biomedical application. Herein, a series of acceptor-π-acceptor type (A1-π-A2) type SPs were synthesized. The diketopyrrolopyrrole (DPP) and thiophene are used as A1 electron accepting block and π-bridge, and the chemical structure of A2 unit was variable. The SPs were formulated into PEGylated nanoparticles, which ensured these SP-based nanoparticles (SP@NPs) exhibited similar size, shape, and physiological stability. Thus, the chemical structure of A2 unit was the only variable. The effects of the SP chemical structures are carefully and comprehensively evaluated through both in vitro and in vivo experiments. Our results demonstrated the chemical structure of A2 unit simultaneously impact their absorption spectra and photothermal (PT) conversion efficiency, which finally determined their PTT and PAI performances. Among these A2 acceptors, thieno[3,2-b]thiophene (TT) unit exhibited the best in vitro and in vivo anticancer efficacies and PAI performances. This study not only provides molecular insights into the design of efficient SPs for PTT and PAI but also highlights the flexibility and potential of SP@NPs for biomedical application. Thus, SP@NPs can act as a versatile nanoplatform for the development of novel light intensive imaging and therapeutic approaches.

Silibinin: an old drug for hematological disorders.

INTRODUCTION: Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases. Recent research endeavors suggest that silibinin may function diversely and serve as a novel therapy for hematological disorders. AREAS COVERED: It discovered several interesting viewpoints in the widely studied mechanisms of silibinin in the hematological disorders. EXPERT COMMENTARY: In this report, we review the up-to-date findings of more potency roles of silibinin in ß-thalassemia (ß-TM), acute myeloid leukemia (AML), anaplastic large cell lymphoma (ALCL) and multiple myelomas (MM) therapy and attempt to clarify the mechanisms underlying its effects. There are two viewpoints: First, The functional mechanisms of silibinin in AML cells via regulating cell differentiation to exert anti-cancer effect; Second, combination treatment strategy may be a good choice.

Ultrastable Near-Infrared Conjugated-Polymer Nanoparticles for Dually Photoactive Tumor Inhibition.

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low-bandgap donor-acceptor (D-A)-type conjugated-polymer nanoparticles (CP-NPs) are developed to afford a highly efficient singlet-to-triplet transition and photothermal conversion for near-infrared (NIR) light-induced photodynamic (PDT)/photothermal (PTT) treatment. CP-NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP-NPs undergo singlet-to-triplet intersystem crossing through charge transfer in the excited D-A system and simultaneous nonradiative decay from the electron-deficient electron acceptor isoindigo derivative under single-wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP-NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light-triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP-NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof-of-concept design of D-A-type conjugated-polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.

Chemotherapy-related risk management toward safe administration of medications: Apply failure mode and effects analysis to reduce the incidence of chemotherapy errors.

Chemotherapy is considered a high-risk procedure where system failures are more likely to occur. Failure mode and effects analysis (FMEA) is a systematic, multidisciplinary team-based approach to error prevention. We described our experience of using FMEA as a prospective risk-management technique throughout the chemotherapy process. The occurrence, detectability and severity were assessed. Fifteen potential risk factors associated with 10 failure modes were identified. Improvement measures were proposed according to risk priority number. A computerized physician order entry (CPOE) and complete prescription audit system (CPAS) were introduced to reduce potential risks during chemotherapy. Introduction of this system was associated with a decrease from 2.60% to 0.60%. As a result, FMEA is a useful tool to evaluate potential risk in healthcare processes.