Explore the vast range of titles available.

Alterations in membrane proteins (MPs) and their regulated pathways have been established as cancer hallmarks and extensively targeted in clinical applications. However, the analysis of MP-interacting proteins and downstream pathways across human malignancies remains challenging. Here, we present a systematically integrated method to generate a resource of cancer membrane protein-regulated networks (CaMPNets), containing 63,746 high-confidence protein–protein interactions (PPIs) for 1962 MPs, using expression profiles from 5922 tumors with overall survival outcomes across 15 human cancers. Comprehensive analysis of CaMPNets links MP partner communities and regulated pathways to provide MP-based gene sets for identifying prognostic biomarkers and druggable targets. For example, we identify CHRNA9 with 12 PPIs (e.g., ERBB2) can be a therapeutic target and find its anti-metastasis agent, bupropion, for treatment in nicotine-induced breast cancer. This resource is a study to systematically integrate MP interactions, genomics, and clinical outcomes for helping illuminate cancer-wide atlas and prognostic landscapes in tumor homo/heterogeneity. Membrane proteins have been implicated in cancers, but studying the downstream effects of their perturbation remains challenging. Here, the authors map the membrane protein-regulated network of 15 cancers, a resource for prognostic biomarker development and druggable target identification.

Human triple-negative breast cancer (TNBC) is the most aggressive and poorly understood subclass of breast cancer. Glucose transporters (GLUTs) are required for glucose uptake in malignant cancer cells and are ideal targets for cancer therapy. To determine whether the inhibition of GLUTs could be used in TNBC cell therapy, the apple polyphenol phloretin (Ph) was used as a specific antagonist of GLUT2 protein function in human TNBC cells. Interestingly, we found that Ph (10–150 μM, for 24 h) inhibited cell growth and arrested the cell cycle in MDA-MB-231 cells in a p53 mutant-dependent manner, which was confirmed by pre-treatment of the cells with a p53-specific dominant-negative expression vector. We also found that Ph treatment (10–150 μM, for 24 h) significantly decreased the migratory activity of the MDA-MB-231 cells through the inhibition of paxillin/FAK, Src, and alpha smooth muscle actin (α-sMA) and through the activation of E-cadherin. Furthermore, the anti-tumorigenic effect of Ph (10, 50 mg/kg or DMSO twice a week for six weeks) was demonstrated in vivo using BALB/c nude mice bearing MDA-MB-231 tumor xenografts. A decrease in N-cadherin, vimentin and an increase in p53, p21 and E-cadherin were detected in the tumor tissues. In conclusion, inhibition of GLUT2 by the apple polyphenol Ph could potentially suppress TNBC tumor cell growth and metastasis. [Display omitted] •Human triple-negative breast cancer (TNBC) is the most aggressive and poorly understood subclass of breast cancer.•Glucose transporters (GLUTs) are required for glucose uptake in malignant cancer cells and are ideal targets for cancer therapy.•Ph (10–150 μM, for 24 h) inhibited cell growth, migration, and arrested the cell cycle in MDA-MB-231 cells.•The anti-tumorigenic effect of Ph (10, 50 mg/kg or DMSO twice a week for six weeks) was demonstrated in vivo using BALB/c nude mice bearing MDA-MB-231 tumor xenografts.•Inhibition of GLUT2 by the apple polyphenol Ph could potentially suppress TNBC tumor cell growth and metastasis.

(1) Background: Psoriasis is a T helper 1/T helper 17 cells-involved immune-mediated genetic disease. Lithospermic acid, one of the major phenolic acid compounds of Danshen, has antioxidation and anti-inflammation abilities. Due to the inappropriate molecular weight for topical penetration through the stratum corneum, lithospermic acid was loaded into the well-developed microemulsion delivery system for IMQ-induced psoriasis-like dermatitis treatment. (2) Methods: BALB/c mice were administered with topical imiquimod to induce psoriasis-like dermatitis. Skin barrier function, disease severity, histology assessment, autophagy-related protein expression, and skin and spleen cytokine expression were evaluated. (3) Results: The morphology, histopathology, and skin barrier function results showed that 0.1% lithospermic acid treatment ameliorated the IMQ-induced psoriasis-like dermatitis and restored the skin barrier function. The cytokines array results confirmed that 0.1% lithospermic acid treatment inhibited the cutaneous T helper-17/Interleukin-23 axis related cytokines cascades. (4) Conclusions: The results implied that lithospermic acid might represent a possible new therapeutic agent for psoriasis treatment.

The purpose of this review is to update and discuss key findings from in vitro and in vivo studies on apple and its biocompounds, with a special focus on its anticancer role. Several studies have proposed that apple and its extracts exhibit a variety of biological functions that may contribute to health benefits including beneficial effects against chronic heart and vascular disorders, respiratory and pulmonary dysfunction, diabetes, obesity, and cancer. In this review, we summarize the molecular mechanism(s) of various components in apple, as established in previous studies that indicated their growth-inhibitory effects in various cancer cell types. Moreover, an attempt is made to delineate the direction of future studies that could lead to the development of apple components as a potent chemopreventive/chemotherapeutic agent against cancer. [Display omitted] •Apple polyphenols and cell proliferation.•Apple polyphenols inhibit cell migration and invasion.•Apple polyphenols induce apoptotic cancer cell death.•Signaling molecules and disease protection effects of phloretin.•Apple polyphenols induce anticancer effects in animal models.

Cigarette smoking is associated with an increased risk of melanoma metastasis. Smokers show higher PD-L1 expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Here, we investigate whether nicotine, a primary constituent of tobacco, induces PD-L1 expression and promotes melanoma cell proliferation and migration, which is mediated by the α9 nicotinic acetylcholine receptor (α9-nAChR). α9-nAChR overexpression in melanoma using melanoma cell lines, human melanoma tissues, and assessment of publicly available databases. α9-nAChR expression was significantly correlated with PD-L1 expression, clinical stage, lymph node status, and overall survival (OS). Overexpressing or knocking down α9-nAChR in melanoma cells up- or downregulated PD-L1 expression, respectively, and affected melanoma cell proliferation and migration. Nicotine-induced α9-nAChR activity promoted melanoma cell proliferation through stimulation of the α9-nAChR-mediated AKT and ERK signaling pathways. In addition, nicotine-induced α9-nAchR activity promoted melanoma cell migration via activation of epithelial-mesenchymal transition (EMT). Moreover, PD-L1 expression was upregulated in melanoma cells after nicotine treatment via the transcription factor STAT3 binding to the PD-L1 promoter. These results highlight that nicotine-induced α9-nAChR activity promotes melanoma cell proliferation, migration, and PD-L1 upregulation. This study may reveal important insights into the mechanisms underlying nicotine-induced melanoma growth and metastasis through α9-nAChR-mediated carcinogenic signals and PD-L1 expression.

The performance of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for identifying acute hemorrhagic stroke in Taiwan's National Health Insurance claims database has not been assessed. This study aimed to construct and validate the case definitions for acute hemorrhagic stroke based on ICD-10-CM diagnostic codes. From January 2018 to December 2019, all inpatient records with ICD-10-CM code of I60 or I61 in any field of the discharge diagnoses were retrieved from the hospitalization claims data and all hospitalizations with a final diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) were identified from the stroke registry databases. The clinical diagnosis in the stroke registry was treated as the reference standard. For hospitalizations not recorded in the stroke registry, manual review of the medical records and images was done to ascertain the diagnosis. The positive predictive value (PPV) and sensitivity of various case definitions for acute hemorrhagic stroke were estimated. Among the 983 hospitalizations, 860, 111, and 12 were determined to be true-positive, false-positive, and false-negative episodes of acute hemorrhagic stroke, respectively. The PPV and sensitivity of the ICD-10-CM codes of I60 or I61 for identifying acute hemorrhagic stroke were 88.6% and 98.6%, respectively. The PPV increased to 98.2%, whereas the sensitivity decreased to 93.1% when acute hemorrhagic stroke was defined as hospitalizations in which the primary diagnosis field contained I60 or I61. Hemorrhagic transformation of ischemic stroke and concomitant cerebrovascular diseases other than SAH or ICH were the main reasons for a false-positive and false-negative diagnosis of acute hemorrhagic stroke, respectively. This study demonstrated the performance of ICD-10-CM codes for identifying acute hemorrhagic stroke and may offer a reference for future claims-based stroke studies.

Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection.

Objective: This study aimed to compare the pregnancy stress among pregnant women in receiving tocolytic and non-tocolytic treatments where both used complementary medicine. Methods: A cross-sectional survey was conducted among 35 pregnant women receiving tocolytic treatment and 35 receiving non-tocolytic treatment, where both used complementary medicine in a medical center in central Taiwan. A basic information questionnaire that contained demographic variables and types of complementary medicine used and the Pregnancy Stress Rating Scale were used for the analysis. Results: The types of complementary medicines were surveyed using the multiple-choice questionnaire. Natural products (77.5%) were most commonly used by pregnant women receiving tocolytic treatment, followed by alternative medicine (13.75%), manipulative and body-based practices (5%), and mind and body medicine (3.75%). In pregnant women who were receiving non-tocolytic treatment, natural products (59.1%) were most commonly used, followed by manipulative and body-based practices (16.4%), alternative medicine (15.4%), mind and body medicine (7.3%), and energy therapy (1.8%). According to the analysis of covariance test results, while both used complementary medicine in groups, pregnant women receiving tocolytic treatment were less stressed than those who were receiving non-tocolytic treatment (Pregnancy Stress Rating Scale score, p = 0.038), especially in dimension 2 (stress caused by infant care and changes in family relationships) ( p = 0.015) and dimension 5 (stress caused by changes in physical appearance and function) ( p = 0.008), which showed statistically significant differences ( p < 0.05). Linear regression analysis results showed that the gestational age significantly associated with pregnancy stress (Pregnancy Stress Rating Scale score, p = 0.029; dimension 2, p = 0.016; and dimension 5, p = 0.001). Conclusion: Among both who used complementary medicine, pregnancy stress was significantly lower in pregnant women who were receiving tocolytic treatment than in those who were receiving non-tocolytic treatment. This finding can be used as a reference for future pregnant women’s health studies.

Background Melasma is a therapeutically challenging hyperpigmented skin condition. Currently, there is a lack of in vivo observation regarding changes in melanin and dendritic melanocytes after laser treatment. Objective To investigate alterations in melanin and melanocytes in melasma before and after laser treatment using optical coherence tomography (OCT). Methods Eight female melasma patients were enrolled in Taiwan. Based on the baseline OCT scans, the patients were categorized into either epidermal‐type or mixed‐type melasma and were assigned different treatment protocols accordingly. Sequential OCT images were collected from melasma lesions and normal skin at baseline, Week 4 and Week 8. Results After 8 weeks of laser treatment, the mean Melasma Area Severity Index (MASI) score improved from 10.92 to 6.30. Results from OCT showed no significant changes in the normalized density, area, or intensity of melanin in both lesional and normal skin. At baseline, the mean length of dendritic melanocytes in the affected skin was 15% longer than those in normal skin; at Week 8, the mean length of lesional dendritic melanocytes became the same as those in normal skin. Additionally, the mean width of dendritic melanocytes decreased from being 4% wider to only 2% wider than those in normal skin. Conclusion After 8 weeks of treatment, an improvement of MASI score was noted, mainly attributable to a reduction in lesional area. OCT showed no notable change regarding melanin, but a decrease in length and width of dendritic melanocytes was noted in the lesional skin of melasma patients.

The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms.