The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer.

Abnormal expression of ACSL members 1, 3, 4, 5, and 6 is frequently seen in human cancer; however, their clinical relevance is unclear. In this study, we analyzed the expression of ACSLs and investigated the effects of the ACSL inhibitor Triacsin C (TC) in lung cancer. We found that, compared to normal human bronchial epithelial (NHBE) cells, ACSL1, ACSL4, and ACSL6 were highly expressed, while ACSL3 and ACSL5 were lost in the majority of lung cancer cell lines. ACSL activity was associated with the expression levels of the ACSLs. In primary lung tumors, a higher expression of ACSL1, ACSL4, and ACSL5 was significantly correlated with adenocarcinoma (ADC). Moreover, ACSL5 was significantly reversely related to the proliferation marker Ki67 in low-grade tumors, while ACSL3 was positively associated with Ki67 in high-grade tumors. Combination therapy with TC and Gemcitabine enhanced the growth-inhibitory effect in EGFR wild-type cells, while TC combined with EGFR-TKIs sensitized the EGFR-mutant cells to EGFR-TKI treatment. Taken together, the data suggest that ACSL1 may be a biomarker for lung ADC, and ACSL1, ACSL4, and ACSL5 may be involved in lung cancer differentiation, and TC, in combination with chemotherapy or EGFR-TKIs, may help patients overcome drug resistance.

The Application of Membrane Separation Technology in the Pharmaceutical Industry.

With the advancement in membrane technology, membrane separation technology has been found increasingly widespread applications in the pharmaceutical industry. It is utilized in drug separation and purification, wastewater treatment, and the recycling of wastewater resources. This study summarizes the application history of membrane technology in the pharmaceutical industry, presents practical engineering examples of its applications, analyzes the various types of membrane technologies employed in the pharmaceutical sector, and finally, highlights the application cases of renowned international and Chinese membrane technology companies in the pharmaceutical field.

Genetic analysis of potential biomarkers and therapeutic targets associated with ferroptosis from bronchopulmonary dysplasia.

Ferroptosis is a recently identified form of cell death that is distinct from the conventional modes such as necrosis, apoptosis, and autophagy. Its role in bronchopulmonary dysplasia (BPD) remains inadequately understood. To address this gap, we obtained BPD-related RNA-seq data and ferroptosis-related genes (FRGs) from the GEO database and FerrDb, respectively. A total of 171 BPD-related differentially expressed ferroptosis-related genes (DE-FRGs) linked to the regulation of autophagy and immune response were identified. Least absolute shrinkage and selection operator and SVM-RFE algorithms identified 23 and 14 genes, respectively, as marker genes. The intersection of these 2 sets yielded 9 genes (ALOX12B, NR1D1, LGMN, IFNA21, MEG3, AKR1C1, CA9, ABCC5, and GALNT14) with acceptable diagnostic capacity. The results of the functional enrichment analysis indicated that these identified marker genes may be involved in the pathogenesis of BPD through the regulation of immune response, cell cycle, and BPD-related pathways. Additionally, we identified 29 drugs that target 5 of the marker genes, which could have potential therapeutic implications. The ceRNA network we constructed revealed a complex regulatory network based on the marker genes, further highlighting their potential roles in BPD. Our findings offer diagnostic potential and insight into the mechanism underlying BPD. Further research is needed to assess its clinical utility.

Prevalence and associated factors of alexithymia among people living with HIV/AIDS in China: a cross-sectional study.

BACKGROUND: Alexithymia is common and causes serious harm to people living with HIV/AIDS. Therefore, this study aimed to examine its prevalence and associated factors among people living with HIV/AIDS in China. METHODS: A cross-sectional study was conducted in two designated AIDS medical institutions in Harbin, China between January and December 2019. In total, 767 participants completed the 20-item Toronto Alexithymia Scale, the University of California Los Angeles Loneliness short-form, the Patient Health Questionnaire-9, the HIV Treatment Regimen Fatigue Scale, and the Alcohol Use Disorders Identification Test-Consumption. The participants responded to several questions regarding their demographic characteristics, life satisfaction, disease-related economic burden, and their antiretroviral therapy (ART) side effects. Multivariate logistic regression assessed the relationship between alexithymia and associated factors. Odds ratios (OR) and 95% confidence intervals (CI) for OR were calculated. RESULTS: Approximately 36.1% of the participants were classified as having alexithymia. After adjusted age and education, the logistic regression model indicated that disease-related economic burden (OR = 1.477, 95% CI = 1.155-1.888), ART side effects (OR = 1.249, 95% CI = 1.001-1.559), loneliness (OR = 1.166, 95% CI = 1.101-1.236), and HIV treatment regimen fatigue (OR = 1.028, 95% CI = 1.017-1.039) were positively associated with alexithymia. CONCLUSIONS: The mental health problems of people living with HIV/AIDS are essential to understand and deserve attention. Disease-related economic burdens are major associated factors. Multiple actors should provide better services and guarantees for patients.

Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy.

The farnesoid-X receptor (FXR), a member of the nuclear hormone receptor superfamily, can be activated by bile acids (BAs). BAs binding to FXR activates BA signaling which is important for maintaining BA homeostasis. FXR is differentially expressed in human organs and exists in immune cells. The dysregulation of FXR is associated with a wide range of diseases including metabolic disorders, inflammatory diseases, immune disorders, and malignant neoplasm. Recent studies have demonstrated that FXR influences tumor cell progression and development through regulating oncogenic and tumor-suppressive pathways, and, moreover, it affects the tumor microenvironment (TME) by modulating TME components. These characteristics provide a new perspective on the FXR-targeted therapeutic strategy in cancer. In this review, we have summarized the recent research data on the functions of FXR in solid tumors and its influence on the TME, and discussed the mechanisms underlying the distinct function of FXR in various types of tumors. Additionally, the impacts on the TME by other BA receptors such as takeda G protein-coupled receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and muscarinic receptors (CHRM2 and CHRM3), have been depicted. Finally, the effects of FXR agonists/antagonists in a combination therapy with PD1/PD-L1 immune checkpoint inhibitors and other anti-cancer drugs have been addressed.

Tumor-Intrinsic PD-L1 Exerts an Oncogenic Function through the Activation of the Wnt/ß-Catenin Pathway in Human Non-Small Cell Lung Cancer.

Programmed death ligand 1 (PD-L1) strongly inhibits T cell activation, thereby aiding tumors in escaping the immune response. PD-L1 inhibitors have proven to be effective in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). Yet, the knowledge regarding the biological function of tumor-intrinsic PD-L1 in lung cancer remains obscure. In our study, we set the goal of determining the function of PD-L1 using overexpression and knockdown strategies. PD-L1 silencing resulted in decreased migratory and invasive ability of tumor cells, together with attenuated colony-forming capacity. Ectopic expression of PD-L1 showed the opposite effects, along with increased activities of MAPK and Wnt/ß-catenin pathways, and the upregulation of Wnt/ß-catenin target genes. Additionally, overexpression of PD-L1 was associated with dysregulated cellular and exosomal miRNAs involved in tumor progression and metastasis. In primary lung tumors, immunohistochemistry revealed that both PD1 and PD-L1 were highly expressed in squamous cell carcinoma (SCC) compared to adenocarcinoma (p = 0.045 and p = 0.036, respectively). In SCC, PD1 expression was significantly associated with tumor grading (p = 0.016). Taken together, our data suggest that PD-L1 may exert an oncogenic function in NSCLC through activating Wnt/ß-catenin signaling, and may act as a potential diagnostic marker for lung SCC.

Diterpenoid alkaloids isolated from Delphinium trichophorum alleviate pulmonary fibrosis via the TGF-ß/Smad pathway in 3T6 and HFL-1 cells.

Delphinium trichophorum Franch (DTF), a species endemic to China, has been widely used for centuries in Tibet as an indigenous medicine for treating cough, pneumonia, and pulmonary fibrosis. Hetisine-type C20-diterpenoid alkaloids have been reported to be characteristic and active ingredients. Herein, five ones with relatively high contents in D. trichophorum, including 2α,11α,13ß-triacetylhetisine (DTF1), trichodelphinine A (DTF2), trichodelphinine D (DTF3), 2α-acetyl-11α,13ß-dihydroxyhetisine (DTF4), and trichodelphinine C (DTF5), were investigated for anti-fibrosis effects using fibroblasts induced by TGF-ß1 or LPS for the first time. The results showed that all five tested compounds decreased hydroxyproline (HYP) levels and inhibited the abnormal proliferation of 3T6 and HFL-1 cells induced by either TGF-ß1 or LPS. Moreover, DTF1 and DTF2 attenuated the production of collagen (Col-1 and Col-3) at relatively low doses, suggesting their higher efficiency among the five alkaloids. Based on large-scale ligand-based pharmacophore modeling, TGFBR1 was screened as a potential target for these tested alkaloids. The molecular docking results also exhibited high-affinity interactions between TGFBR1 and five alkaloids, especially DTF1 and DTF2. Further experiments revealed that DTF1 and DTF2 could inhibit the expression of TGF-ß1 and α-SMA and the phosphorylation of Smad3 and Smad4 while restoring the expression of Smad7 protein. Overall, DTF1 and DTF2 may reduce collagen generation and delay the development of pulmonary fibrosis by inhibiting the activation of the TGF-ß/Smad signaling pathway. Our results provide experimental and theoretical evidence for DTF1 and DTF2 as superior candidates for further development of anti-fibrotic drugs.

Epithelial Membrane Protein 1 Promotes Sensitivity to RSL3-Induced Ferroptosis and Intensifies Gefitinib Resistance in Head and Neck Cancer.

Epithelial membrane protein (EMP1), a member of the peripheral myelin protein (PMP22) family, is involved in the development of various human malignancies. However, the expression level of EMP1 and its functional role in head and neck squamous cell carcinoma (HNSCC) remain unclear to date. Ferroptosis, a newly characterized form of regulated cell death, plays an essential role in tumorigenesis. In this study, we aimed to investigate the expression levels of EMP1 in HNSCC and normal tissues, as well as to identify the function of EMP1 in regulating ferroptosis during the progression of HNSCC. To further explore the biological function of EMP1 in vitro, transient transfection was used to overexpress EMP1 in the HNSCC cell lines Hep2 and Detroit562. Functionally, our results indicated that EMP1 overexpression could not affect the initiation of ferroptosis directly but reinforced RSL3-induced ferroptosis on HNSCC cells. Furthermore, mechanical study indicated that EMP1 mediated the ferroptosis via cell density-regulated Hippo-TAZ pathway and regulated the expression of Rac1 and NOX1. In addition, our study demonstrated that EMP1 overexpression could promote gefitinib resistance by targeting the MAPK pathway. In summary, our findings indicate that EMP1 may act as an oncogene and serve as a therapeutic target against malignant progression of HNSCC.

Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial.

BACKGROUND: Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD. METHODS: This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score. DISCUSSION: This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046755 . Registered on May 28, 2021.

Diterpenoid Alkaloids Isolated from Delphinium brunonianum and Their Inhibitory Effects on Hepatocytes Lipid Accumulation.

This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from Delphinium brunonianum. Four novel diterpenoid alkaloids, brunodelphinine B-E, were isolated from D. brunonianum together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids-brunodelphinine E (4), delbruline (5), lycoctonine (7), delbrunine (8), and sharwuphinine A (12)-exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A (12) displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of D. brunonianum and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.

Authentication and Quality Assessment of Plumeriae Rubrae Flos by UHPLC-QTOF-MS/MS and UHPLC-DAD Combined With Chemometrics.

BACKGROUND: Plumeriae rubrae flos, the dried flowers of Plumeria rubra cv. acutifolia (PRCA), is one of the most important materials of herbal tea in China. Recently, due to the lack of effective quality evaluation standards, it has been found that Plumeria rubra (PR) and Plumeria rubra var. alba (PRVA) were pretended to be PRCA in herbal material markets. OBJECTIVE: To establish an effective method for comprehensive quality assessment on plumeriae rubrae flos, and distinguishing PRCA from its common adulterants, PR and PRVA. METHOD: In this study, a method combined application of ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS), UHPLC with a diode array detector (UHPLC-DAD), and chemometrics was developed for qualitative and quantitative analysis of PRCA, PR, and PRVA, based on their multiple components. RESULTS: A total of 26 components were identified by UHPLC-QTOF-MS/MS, including nine flavonoids, eight iridoids, seven phenolic acids, and two coumarins from PRCA. Quantified fingerprints were established and validated using UHPLC-DAD based on 18 chemical markers in PRCA, PR, and PRVA samples. The multivariate statistical analysis of quantitative results demonstrated clear discrimination of PRCA, PR, and PRVA, which indicated that isoquercetin, luteolin-3'-O-ß-D-glucoside, 15-demethylplumieride P-E-coumarate, and 4-O-beta-glucopyranosyl-cis-coumaric acid could be considered the most obvious characteristic components for distinguishing PRCA from PR and PRVA. CONCLUSIONS: A combination of quantitative fingerprint and chemometrics analysis provided an effective and reliable strategy for the quality control of PRCA. HIGHLIGHTS: The current study was prospected to apply a comprehensive quality control method for plumeriae rubrae flos.

HAGLROS promotes cell proliferation and angiogenesis and inhibits apoptosis by activating multiple signaling pathways in LSCC cells.

BACKGROUND: HAGLROS is a long noncoding RNA involving in the development of a variety of cancers, but its mechanism of action in laryngeal squamous cell carcinomas (LSCC) is still unclear. We aim to unveil the effect and mechanism of HAGLROS on LSCC. METHODS: The expression of HAGLROS in LSCC patients' tissues, serum, and LSCC cell lines was quantified by quantitative real-time PCR. AMC-HN-8 and SNU-46 cells were transfected with the overexpression plasmid of HAGLROS and shHAGLROS, and the functional assay (colony formation assays, flow cytometry, and tube formation) was performed. Western blot was used to determine the expressions of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), P27 and cleaved caspase-3, as well as phosphorylated-c-Jun-N-terminal kinase (p-JNK), JNK, phosphorylated-extracellular signal-regulated kinase 1/2 (p-Erk1/2), Erk1/2, phosphorylated-protein kinase B (p-AKT) and AKT. RESULTS: HAGLROS was highly expressed in LSCC tissues and cells, and it was correlated to lymph node, tumor depth, and clinical stage of LSCC patients. The proliferation ability of LSCC cells was higher than that of HuLa-PC cells. Meanwhile, HAGLROS overexpression promoted the abilities of proliferation and angiogenesis and reduced apoptosis, whereas silencing of HAGLROS exerted the opposite effects in LSCC cell lines. Moreover, overexpressed HAGLROS upregulated the expressions of VEGF and PCNA yet downregulated the expressions of P27 and cleaved caspase-3 by activating Erk1/2 and AKT or JNK signaling pathways in different LSCC cell lines. CONCLUSION: Overexpressed HAGLROS promoted the proliferation and angiogenesis yet inhibited apoptosis of LSCC cells by activating Erk1/2 and AKT or JNK signaling pathways.

Tumor-derived exosomes: Key players in non-small cell lung cancer metastasis and their implication for targeted therapy.

Exosomes represent extracellular vesicles of endocytic origin ranging from 30 to 100 nm that are released by most of eukaryotic cells and can be found in body fluids. These vesicles in carrying DNA, RNA, microRNA (miRNA), Long noncoding RNA, proteins, and lipids serve as intercellular communicators. Due to their role in crosstalk between tumor cells and mesenchymal stroma cells, they are vital for tumor growth, progression, and anticancer drug resistance. Lung cancer is a global leading cause of cancer-related deaths with 5-year survival rates of about 7% in patients with distant metastasis. Although the implementation of targeted therapy has improved the clinical outcome of nonsmall cell lung cancer, drug resistance remains a major obstacle. Lung tumor-derived exosomes (TDEs) conveying molecular information from tumor cells to their neighbor cells or cells at distant sites of the body activate the tumor microenvironment (TME) and facilitate tumor metastasis. Exosomal miRNAs are also considered as noninvasive biomarkers for early diagnosis of lung cancer. This review summarizes the influence of lung TDEs on the TME and metastasis. Their involvement in targeted therapy resistance and potential clinical applications are discussed. Additionally, challenges encountered in the development of exosome-based therapeutic strategies are addressed.

Genome-wide exploration of a pyroptosis-related gene module along with immune cell infiltration patterns in bronchopulmonary dysplasia.

Pyroptosis plays a crucial role in bronchopulmonary dysplasia (BPD) and is associated with various lung injury illnesses. However, the function of pyroptosis-related genes (PRGs) in BPD remains poorly understood. The gene expression omnibus (GEO) database was searched for information on genes associated with BPD. Twenty-five BPD-related DE-PRGs were identified, all of which were closely associated with pyroptosis regulation and immunological response. LASSO and SVM-RFE algorithms identified CHMP7, NLRC4, NLRP2, NLRP6, and NLRP9 among the 25 differentially expressed PRGs as marker genes with acceptable diagnostic capabilities. Using these five genes, we also generated a nomogram with excellent predictive power. Annotation enrichment analyses revealed that these five genes may be implicated in BPD and numerous BPD-related pathways. In addition, the ceRNA network showed an intricate regulatory link based on the marker genes. In addition, CIBERSORT-based studies revealed that alterations in the immunological microenvironment of BPD patients may be associated with the marker genes. We constructed a diagnostic nomogram and gave insight into the mechanism of BPD. Its diagnostic value for BPD must be evaluated in further research before it can be used in clinical practice.

Epidemiological trend in scarlet fever incidence in China during the COVID-19 pandemic: A time series analysis.

Objective: Over the past decade, scarlet fever has caused a relatively high economic burden in various regions of China. Non-pharmaceutical interventions (NPIs) are necessary because of the absence of vaccines and specific drugs. This study aimed to characterize the demographics of patients with scarlet fever, describe its spatiotemporal distribution, and explore the impact of NPIs on the disease in the era of coronavirus disease 2019 (COVID-19) in China. Methods: Using monthly scarlet fever data from January 2011 to December 2019, seasonal autoregressive integrated moving average (SARIMA), advanced innovation state-space modeling framework that combines Box-Cox transformations, Fourier series with time-varying coefficients, and autoregressive moving average error correction method (TBATS) models were developed to select the best model for comparing between the expected and actual incidence of scarlet fever in 2020. Interrupted time series analysis (ITSA) was used to explore whether NPIs have an effect on scarlet fever incidence, while the intervention effects of specific NPIs were explored using correlation analysis and ridge regression methods. Results: From 2011 to 2017, the total number of scarlet fever cases was 400,691, with children aged 0-9 years being the main group affected. There were two annual incidence peaks (May to June and November to December). According to the best prediction model TBATS (0.002, {0, 0}, 0.801, {<12, 5>}), the number of scarlet fever cases was 72,148 and dual seasonality was no longer prominent. ITSA showed a significant effect of NPIs of a reduction in the number of scarlet fever episodes (ß2 = -61526, P < 0.005), and the effect of canceling public events (c3) was the most significant (P = 0.0447). Conclusions: The incidence of scarlet fever during COVID-19 was lower than expected, and the total incidence decreased by 80.74% in 2020. The results of this study indicate that strict NPIs may be of potential benefit in preventing scarlet fever occurrence, especially that related to public event cancellation. However, it is still important that vaccines and drugs are available in the future.

Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis.

Fatty acids are energy substrates and cell components which participate in regulating signal transduction, transcription factor activity and secretion of bioactive lipid mediators. The acyl-CoA synthetases (ACSs) family containing 26 family members exhibits tissue-specific distribution, distinct fatty acid substrate preferences and diverse biological functions. Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis, designated as the bidirectional relationship between the gut, microbiome and liver, is closely associated with a range of human diseases including metabolic disorders, inflammatory disease and carcinoma in the gastrointestinal tract and liver. In this review, we depict the role of ACSs in fatty acid metabolism, possible molecular mechanisms through which they exert functions, and their involvement in hepatocellular and colorectal carcinoma, with particular attention paid to long-chain fatty acids and small-chain fatty acids. Additionally, the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed. Moreover, the development of potentially therapeutic small molecules, proteins and compounds targeting ACSs in cancer treatment is summarized.

Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer.

Fibulins (FBLNs), interacting with cell adhesion receptors and extracellular matrix (ECM) components, play multiple roles in ECM structures and tissue functions. Abnormal expression of FBLN2, one of the fibulin family members, contributes to tumor initiation and development. However, the function of FBLN2 in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we found that FBLN2 was downregulated in 9 out of 11 lung cancer cell lines compared to normal bronchial epithelial cells, which was associated with DNA hypermethylation. Primary lung squamous cell carcinoma expressed significantly more FBLN2 protein compared to adenocarcinoma (p = 0.047). Ectopic expression of FBLN2 led to decreased cell proliferation, migration and invasion, accompanied by inactivated MAPK/ERK and AKT/mTOR pathways, while FBLN2 siRNA knockdown resulted in an opposite biological behaviour in NSCLC cells. Additionally, overexpression of FBLN2 led to dysregulation of cell adhesion molecules, ECM markers and a panel of lysate/exosome-derived-microRNAs, which are involved in cell adhesion and ECM remodelling. Taken together, our data indicate that FBLN2 is methylated and exerts a tumor suppressor function through modulation of MAPK/ERK and AKT pathways and regulation of cell adhesion and ECM genes. Moreover, FBLN2 might be a potential biomarker for the sub-classification of NSCLC.

Pheophorbide co-encapsulated with Cisplatin in folate-decorated PLGA nanoparticles to treat nasopharyngeal carcinoma: Combination of chemotherapy and photodynamic therapy.

The adverse effect and drug resistance of Cisplatin (CDDP) could be potential reduced by delivering in targeted nanoparticles and by combining with adjuvant therapy such as photodynamic therapy. In this study, F/CDPR-NP was formulated and characterized for all the physicochemical, biological and in vivo analysis. The results obtained from various in vitro and biological studies showed that encapsulation of CDDP and PBR in PLGA nanoparticles results in controlled release of encapsulated drugs and exhibited significantly low cell viability in CNE-1 and HNE-1 cancer cells. F/CDPR-NP significantly prolonged the blood circulation of the encapsulated drugs. The AUC of CDDP from F/CDPR-NP (4-fold) was significantly higher compared to that of free CDDP and similarly significantly higher t1/2 for CDDP from F/CDPR-NP was observed. F/CDPR-NP in the presence of laser irradiation showed significant reduction in the tumor burden with low tumor cell proliferations compared to either CDPR-NP or free CDDP indicating the potential of targeted nanoparticles and photodynamic therapy. Overall, combination of treatment modalities and active targeting approach paved way for the higher antitumor activity in nasopharyngeal carcinoma model. The positive results from this study will show new horizon for the treatment of other cancer models.

A UPLC-MS/MS-based metabolomics analysis of the pharmacological mechanisms of rabdosia serra against cholestasis.

BACKGROUND: Rabdosia Serra, the dried aerial parts of Rabdosia serra (Maxim.) Hara (RS) from the Labiatae family, is a traditional Chinese herbal medicine called Xihuangcao. Although RS has been found to exert a therapeutic effect on cholestasis, the underlying molecular mechanism remains unclear. PURPOSE: This study was designed to investigate the pharmacological effect and mechanism of RS on cholestatic rats using metabolomics platform. METHODS: Histopathology and biochemical evaluations were performed to determine the therapeutic effect of RS and developed a rapid metabolite detection technology method based on UPLC-MS/MS to perform metabolomics research. Further, quantitative real-time polymerase chain reaction (RT-qPCR) was used to study the effect of RS on the bile acid metabolism pathway at the transcriptional level. RESULTS: RS significantly reduced the bile flow rates in cholestatic rats and decreased the levels of ALT, AST, TBA, T-BIL, and LDH, which were increased in the model group. Histological analysis showed that RS alleviated the liver injury induced by ANIT. Serum metabolomics results revealed 33 of the 37 biomarkers were found to be significantly altered by ANIT, and 26 were considerably changed following treatment with RS. Metabolic pathway analysis revealed four pathways such as primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, and arachidonic acid and tryptophan metabolism. The bile acid secretion process and the inflammation and oxidative stress processes are the major biochemical reactions following treatment with ANIT and RS. Bile acid-targeted metabolomics study showed that TCA, GCA, GCDCA, and GDCA might be sensitive biomarkers that induced liver injury. we found that treatment with RS regulated the levels of bile acid in the serum and liver and restored the proportion of bile acids, especially CA and conjugated bile acids, such as TCA and GCA, in the bile duct. RS increased the mRNA expression levels of FXR, SHP, BSEP, and MRP2 in livers, and IBABP, OST-α, and OST-ß in the ileum. CONCLUSION: In this study, RS was found to protect the liver by regulating multiple metabolic pathways and promoting the excretion of bile acids. Simultaneously, RS played an essential role in reversing the imbalance of bile acids and protected against cholestasis by regulating the expression of transporters associated with bile acids. We demonstrated the correlation between molecular mechanisms and metabolites, provide a reference for the fabrication of extracts that can be used to treat cholestasis.

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.