Family-based whole exome sequencing of atopic dermatitis complicated with cataracts.

Background: Atopic dermatitis (AD) is a common skin disorder with elevated prevalence. Cataract induced by AD rarely occurs in adolescent and young adult patients, which is also called atopic cataract. Using whole exome sequencing, we aimed to explore genetic alterations among AD and atopic cataract.

Prognostic value of maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis of positron emission tomography/computed tomography in patients with nasopharyngeal carcinoma: A systematic review and meta-analysis.

Background: The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma (NPC) perform as new prognostic factors, but the outcomes of the published articles were inconclusive. In this meta-analysis, we evaluated the prognostic value of SUVmax, MTV, and TLG of PET/CT in patients with NPC.

Methods: Relevant English articles were searched in PubMed and EMBASE.

Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors.

Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.

Combined effects of EGFR and hedgehog signaling blockade on inhibition of head and neck squamous cell carcinoma.

Head and neck cancer, the sixth most common cancer, has poor prognosis and short survival. Anti-epidermal growth factor receptor (EGFR) therapies have been recently developed for the treatment of multiple cancer types. JK184, an inhibitor of Hedgehog pathway, prevents the growth of many tumor cell lines in several studies.

Inhibition of P2X7 Receptor Ameliorates Nuclear Factor-Kappa B Mediated Neuroinflammation Induced by Status Epilepticus in Rat Hippocampus.

P2X7 receptor (P2X7R) has been reported participating in neuroinflammation in multiple neurological diseases. We explored the role of P2X7R in a rat status epilepticus (SE) model induced by coriaria lactone (CL) and its association with neuroinflammation. Thirty minutes after intracerebroventricular infusion with P2X7R antagonists Brilliant blue G (BBG), A-438079, A-740003, or agonists 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), SE was induced by intramuscular injection of CL in Sprague-Dawley rats.

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs.

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients.

Hepatitis B virus X protein promotes hepatocellular carcinoma invasion and metastasis via upregulating thioredoxin interacting protein.

Hepatitis B virus X protein (HBx), a multifunctional protein encoded by the X gene of the hepatitis B virus (HBV) is involved in the metastasis of HBV-associated hepatocellular carcinoma (HCC) through various pathways, including upregulating intracellular reactive oxygen species (ROS). Thioredoxin interacting protein (TXNIP) is a key mediator of intracellular ROS, but its function in HBx-mediated metastasis of HBV-associated HCC is elusive. In the present study, HBV-associated HCC tissues with or without metastasis and HepG2 cells were used to study the function of TXNIP in HBx-mediated metastasis of HBV-associated HCC.

Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors.

The crystal structure of viral infectivity factor (Vif) was reported recently, which makes it possible to design new inhibitors against Vif by structure-based drug design. Through analysis of the protein surface of Vif, the C2 pocket located in the N-terminal was found, which is suit for developing small molecular inhibitors. Then, in our article, fragment-based virtual screening (FBVS) was conducted and a series of fragments was obtained, among which, Zif-1 bearing indole scaffold and pyridine ring can form H-bonds with Tyr148 and Ile155.

Label-free photoacoustic imaging of the cardio-cerebrovascular development in the embryonic zebrafish.

Zebrafish play an important role in biology, pharmacology, toxicology, and medicine. The cardio-cerebrovascular development of zebrafish is particularly critical to understand both brain disorders and cardiovascular diseases in human. In this paper, we applied optical resolution photoacoustic microscopy (ORPAM) to image the whole-body vasculature of the embryonic zebrafish with a special focus on the development of the cardio-cerebrovascular system.

Role of Nicotinamide N-Methyltransferase in Dorsal Striatum in Cocaine Place Preference.

Nicotinamide N-methyltransferase (NNMT) transfers the methyl from S-adenosyl-L-methionine (SAM) to nicotinamide (NA) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide (MeN). NNMT has been implicated in a variety of diseases; however, the role of NNMT in drug addiction is largely unknown. Here, we found that the expression of Nnmt was significantly upregulated in the dorsal striatum (DS) of cocaine-conditioned mice.

The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells.

Prostate cancer is a big threat to male for its poor prognosis and high mortality rate. Natural compounds are important resources of many anticancer drugs. Pomegranate is a kind of antioxidant-rich fruit and its peel and seed has potential anticancer activities.

Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers.

Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy.

Remodeling of brain lipidome in methamphetamine-sensitized mice.

Lipids are predominant components of the brain and key regulators for neural structure and function. The effect of methamphetamine (METH) on behavior, cognition as well as memory has been intensively investigated; however, the impact of METH on brain lipid profiles is largely unknown. Here, we used a global lipidomic approach to investigate brain lipidome of METH-sensitized mice.

Liposomal honokiol induced lysosomal degradation of Hsp90 client proteins and protective autophagy in both gefitinib-sensitive and gefitinib-resistant NSCLC cells.

Honokiol (HK), a natural chemical isolated from Mangnolia officinalis, has shown antitumorigenic activities when used to treat a variety of tumor cell lines. The mechanism of honokiol activity when used to treat gefitinib-sensitive and gefitinib-resistant non-small cell lung cancer (NSCLC) requires elucidation. Here, the presence of liposomal honokiol (LHK) induced apoptotic and antitumor activities in four xenograft models generated using NSCLC cell lines such as HCC827 (gefitinib-sensitive) and H1975 (gefitinib-resistant).

In vitro anticancer effects of two novel phenanthroindolizidine alkaloid compounds on human colon and liver cancer cells.

Malignant cancer is one of the most serious diseases threatening the health of human beings. Natural plant alkaloids exhibit multiple biological functions, including inhibition of cell proliferation, and may have potential anticancer activity. However, most natural alkaloids may not be suitable for human therapies owing to instability, poor dissolubility and potential side effects.

Curcumin exerts its tumor suppressive function via inhibition of NEDD4 oncoprotein in glioma cancer cells.

Glioblastoma is the most common brain cancer in adults. It represents one of the top ten malignant tumors with an average survival time of nine months despite treatments with surgery, radiotherapy and chemotherapy. Curcumin is a phytochemical turmeric isolated from root of the Curcuma longa plant.

In vitro studies of phospholipid-modified PAMAM-siMDR1 complexes for the reversal of multidrug resistance in human breast cancer cells.

The application of RNAi therapeutics is promising in combating several major human diseases including malignant tumors. However, this approach is limited due to its delivery barriers. In this study, we designed a new carrier system loaded with a functional siRNA targeting MDR1 gene to reverse multi-drug resistance (MDR) in human breast cancer MCF-7/ADR cells.

Niclosamide induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in human thyroid cancer in vitro.

The morbidity of thyroid cancer has been rising obviously throughout the world during the past years. Classic treatment procedure is generally curable for low risk differentiated thyroid cancer, but may lead to many postoperative complications. And low-level of thyroid stimulating hormone after surgery has side effects on both cardiovascular system and skeletal system.

Proteomic identification of ERP29 as a key chemoresistant factor activated by the aggregating p53 mutant Arg282Trp.

Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in TP53-expressing cells that were exposed to cisplatin stress.

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for Gene Therapy.

Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence associated with conventional therapy (e.g. surgery, radiation, and chemotherapy).

Assessing the performance of docking scoring function, FEP, MM-GBSA, and QM/MM-GBSA approaches on a series of PLK1 inhibitors.

Over-expressed polo-like kinases 1, a key regulator of cell mitosis, is associated with carcinogenesis and poor prognosis. It is very necessary to develop a reliable computational affinity prediction protocol targeting PLK1. In this study, the performance of different docking scoring function, free energy perturbation, MM-GBSA and QM/MM-GBSA were evaluated.

Improving the pharmacokinetics and tissue distribution of pyrinezolid by self-assembled polymeric micelles.

Antibiotic-resistance by bacteria is a growing global concern within the healthcare field, and it has provided an impetus for continued antimicrobial development. Pyrinezolid (PZ), a novel oxazolidinone compound, can effectively inhibit most gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Though PZ is a promising antimicrobial candidate, the druggability of PZ is limited by its poor water solubility.

Safety and efficacy evaluation of pertuzumab in patients with solid tumors.

Background: The development of targeted therapies benefits patients with certain markers in the treatment of breast cancer. Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. The Food and Drug Administration has approved pertuzumab in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer.