Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.

Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed.

Impact factors of Blastocystis hominis infection in persons living with human immunodeficiency virus: a large-scale, multi-center observational study from China.

Background: Blastocystis hominis (Bh) is zoonotic parasitic pathogen with a high prevalent globally, causing opportunistic infections and diarrhea disease. Human immunodeficiency virus (HIV) infection disrupts the immune system by depleting CD4 T lymphocyte (CD4 T) cell counts, thereby increasing Bh infection risk among persons living with HIV (PLWH). However, the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly understood.

Trichoscopy for early diagnosis and follow-up of pet-related neonatal tinea capitis.

We report infant zigzag hairs as a distinct trichoscopic sign for follow up a case of pet-related newborn tinea capitis due to Microsporum canis. Formation of infant zigzag hairs due to ectothrix M. canis infection may be associated soft neonatal widespread thin hair, which is different from vellus hair and terminal hair.

Bedside Diagnosis for Disseminated Deep Dermatophytosis: a Case Series Study.

Deep cutaneous fungal infections including deep dermatophytosis are responsible for significant morbidity and mortality, especially in immunocompromised patients. Variable and longer turnaround time on tissue culture results delay diagnosis. We sought to seek the fast bedside diagnosis for disseminated deep dermatophytosis by direct microscopy using a blunt scalpel or needle aspiration before biopsy.

Violet colonies of Talaromyces marneffei produce on CHROMagar candida medium.

In the present report, we describe an unusual case of mixed infection of Candida albicans and Talaromyces marneffei in the oral cavity and oropharynx with cutaneous involvement. On the CHROMagar Candida plate, green colonies (identified as C. albicans) and tiny violet colonies (identified as T.

Neuroprotective Effects of Lindleyin on Hydrogen Peroxide-Induced Cell Injury and MPTP-Induced Parkinson's Disease in C57BL/6 Mice.

Oxidative stress (OS) is a crucial factor influencing the development of Parkinson's disease (PD). Here we first reported that Lindleyin (), one of the major components of rhubarb, possessed neuroprotective effects against HO-induced SH-SY5Y cell injury and MPTP-induced PD of C57BL/6 mice. The results showed that can decrease cell death and apoptotic rate induced by HO through inhibiting mitochondrial apoptotic pathway and increasing the activities of SOD, GSH-Px, and CAT as well as decreasing the level of MDA.

Safety of combining vascular endothelial growth factor receptor tyrosine-kinase inhibitors with chemotherapy in patients with advanced non-small-cell lung cancer: A PRISMA-compliant meta-analysis.

Background: Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) have been developed for targeted therapies in non-small-cell lung cancer (NSCLC); moreover, some drug-related toxic reactions among cancer patients have been reported. A meta-analysis of randomized controlled trials (RCTs) to definite the incidence and the risk of grade ≥3 adverse events (AEs), serious and fatal AEs (SAEs and FAEs), with VEGFR-TKIs in advanced/metastatic NSCLC patients was performed.

Methods: A comprehensive literature search was conducted for the clinical trials published up to December 2017.

Favus of Scrotum Due to Trichophyton rubrum in Immunocompetent Patients: A Clinical, Mycological and Ultrastructural Study.

Purpose: To characterize the clinical and mycological features of favus of scrotum due to Trichophyton rubrum.

Methods: A single-site prospective study was carried out in an outpatient dermatology clinic. Microscopic examination and fungal culture were done using skin scrapings.

Effects of PKM2 on global metabolic changes and prognosis in hepatocellular carcinoma: from gene expression to drug discovery.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs.

Comprehensive analysis of gene expression profiles associated with proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) is characterized by neovascularization on the surface of the retina or the optic disc, which is associated with environmental and genetic factors. However, its regulatory mechanism remains to be fully elucidated, particularly at a multiomics level. In the present study, a comprehensive analysis was performed of the gene expression profile of fibrovascular membranes (FVMs) associated with PDR, including an analysis of differentially expressed genes, functional enrichment, and regulation of transcription factors (TFs).

High PKM2 expression is independently correlated with decreased overall survival in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal and malignant types of cancer that affects global human health. The present study aimed to investigate the effect of pyruvate kinase muscle isozyme M2 (PKM2) expression on the clinical features and prognosis of HCC. The present study employed univariate logistic regression to investigate the correlation between PKM2 expression and clinical features.

Comprehensive integrated analysis of gene expression datasets identifies key anti-cancer targets in different stages of breast cancer.

Breast cancer is one of the primary threats to women's health worldwide. However, the molecular mechanisms underlying the development of breast cancer remain to be fully elucidated. The present study aimed to investigate specific target gene expression profiles in breast cancer tissues in general and in different breast cancer stages, as well as to explore their functions in tumor development.

Folate Deficiency and Gene Polymorphisms of MTHFR, MTR and MTRR Elevate the Hyperhomocysteinemia Risk.

Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). We aimed to investigate the joint effect of homocysteine metabolism gene polymorphisms, as well as the folate deficiency on the risk of HHcy in a Chinese hypertensive population.

Methods: This study enrolled 480 hypertensive patients aged 28 - 75 from six hospitals in different Chinese regions from 9/2005 - 12/2005.

Comprehensive tissue-specific gene set enrichment analysis and transcription factor analysis of breast cancer by integrating 14 gene expression datasets.

Breast cancer is the most commonly diagnosed malignancy in women. Several key genes and pathways have been proven to correlate with breast cancer pathology. This study sought to explore the differences in key transcription factors (TFs), transcriptional regulation networks and dysregulated pathways in different tissues in breast cancer.

Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation.

Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary.

Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study.

Background: Dyslipidemia is a well-established risk factor for cardiovascular disease. Serum lipids were affected by several gene polymorphisms, folate, homocysteine and other metabolite levels. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension.

Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition.

Aim: 2-(4,6-Dimethoxy-1,3-dioxoisoindolin-2-yl) ethyl 2-chloroacetate (QSN-10c) is one of isoindolone derivatives with antiproliferative activity against human umbilical vein endothelial cells (HUVECs). The aim of this study was to investigate its antitumor activity in vitro and anti-angiogenic effects in vitro and in vivo.

Methods: K562 leukemic cells and HUVECs were used for in vitro studies.

Four new koumine metabolites in rat liver microsomes.

Four new metabolites M-1 [1,2,18,19-tetradehydro-4-demethyl-3,17-epoxy-7,20(2H,19H)-cyclovobasan], M-2 [1,2,4,21,18,19-hexadehydro-4-demethyl-3,17-epoxy-7,20(2H,19H)-cyclovobasan], M-3 [1,2,18,19-tetradehydro-4-demethyl-4-formaldehyde-3,17-epoxy-7,20(2H,19H)-cyclovobasan], and M-4 [1,2,4,21,18,19-hexadehydro-4-demethyl-4-oxy-3,17-epoxy-7,20(2H,19H)-cyclovobasan] were isolated from the chloroform extract of koumine incubated with phenobarbital-treated rat liver microsomes. The structures of M-1, M-2, M-3, and M-4 were elucidated by spectroscopic methods including ESI-TOF-MS, 1D, and 2D NMR experiments. The metabolic pathway of koumine was proposed.

Antibacterial, antifungal and cytotoxic isoquinoline alkaloids from Litsea cubeba.

Five novel isoquinoline alkaloids (+)-N-(methoxylcarbonyl)-N-nordicentrin (1), (+)-N-(methoxylcarbonyl)-N-norpredicentrine (2), (+)-N-(methoxylcarbonyl)-N-norbulbodione (3), and (+)-N-(methoxylcarbonyl)-N-norisocorydione (4), and (+)-8-methoxyisolaurenine-N- oxide (5) were isolated, together with one known compound, (+)-N-(methoxylcarbonyl)- N-norglaucine (6), from a 70% EtOH extract of the barks of Litsea cubeba. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. Alkaloids 1, 2 and 6 showed antimicrobial activity against the bacterium S.

Depletion of histone deacetylase 3 antagonizes PI3K-mediated overgrowth of Drosophila organs through the acetylation of histone H4 at lysine 16.

Core histone modifications play an important role in chromatin remodeling and transcriptional regulation. Histone acetylation is one of the best-studied gene modifications and has been shown to be involved in numerous important biological processes. Herein, we demonstrated that the depletion of histone deacetylase 3 (Hdac3) in Drosophila melanogaster resulted in a reduction in body size.

E2 ligase dRad6 regulates DMP53 turnover in Drosophila.

The turnover of tumor suppressor p53 is critical for its role in various cellular events. However, the pathway that regulates the turnover of the Drosophila melanogaster DMP53 is largely unknown. Here, we provide evidence for the first time that the E2 ligase, Drosophila homolog of Rad6 (dRad6/Dhr6), plays an important role in the regulation of DMP53 turnover.