Discovery and optimization of novel 4-morpholinothieno[3,2-d]pyrimidine derivatives as potent BET inhibitors for cancer therapy.

The identification of structurally novel and potently active BET inhibitors represents a significant advancement in the field of anticancer therapeutics. In the present investigation, leveraging the outcomes of previous screening endeavors, we successfully optimized and synthesized a novel series of bromodomain and extra-terminal (BET) inhibitors with a 4-morpholinothieno[3,2-d]pyrimidine structure. Among the synthesized compounds, compound 6c emerged as a promising candidate, exhibiting exceptional inhibitory activities against various BET isoform proteins, with IC values ranging from 3.

Smart Design of Mitochondria-Targeted and ROS-Responsive CPI-613 Delivery Nanoplatform for Bioenergetic Pancreatic Cancer Therapy.

Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 () prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613.

A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report.

The pathogenesis of Alzheimer's disease is complex, and early-onset Alzheimer's disease (EOAD) is mostly influenced by genetic factors. Presenilin-1, presenilin-2 (PSEN2), and amyloid precursor protein are currently known as the three main causative genes for autosomal dominant EOAD, with the PSEN2 mutation being the rarest. In this study, we reported a 56-year-old Chinese Han proband who presented with prominent progressive amnesia, aphasia, executive function impairment, and depression 5 years ago.

Zinc(ii)-cyclen coordinative amphiphiles for enhanced gene delivery.

In this study, we developed coordinative amphiphiles for use as novel non-viral DNA vectors. As a modification of a conventional cationic lipid structure, we replaced the cationic head with a zinc(ii)-1,4,7,10-tetraazacyclododecane (Zn-cyclen) complex as a phosphate-directing group, and used biocompatible skeletons (α-tocopherol or cholesterol) as hydrophobic tails. The structure-activity relationship (SAR) was systematically investigated to study the effect of Zn-coordination on the gene transfection between cyclen-based traditional head-tail lipids and Zn(ii)-cyclen coordinative amphiphiles.

Medicated thread moxibustion for alopecia areata: A case report.

Rationale: According to the literature reports and clinical studies on alopecia areata (AA) from 2008 to 2018, most clinical treatments have been oral drugs and external ointments. At present, systemic immunosuppressive therapy has been widely used in AA, but there are various side effects such as elevated liver enzymes, gastrointestinal discomfort, poor drug compliance, and repeated illness. We present a case report describing a traditional medicine treatment for AA that uses an ethnic therapy of Zhuang medicine, a kind of Traditional Chinese Medicine, namely, medicated thread moxibustion.

Inhibitory Effect of Volatiles Emitted From N1-4 on and Aflatoxins in Storage.

Controlling aflatoxigenic and aflatoxins (AFs) in grains and food during storage is a great challenge to humans worldwide. N1-4 isolated from tea rhizosphere soil can produce abundant antifungal volatiles, and greatly inhibited the growth of in un-contacted face-to-face dual culture testing. Gas chromatography tandem mass spectrometry revealed that dimethyl disulfide (DMDS) and methyl isovalerate (MI) were two abundant compounds in the volatile profiles of N1-4.

Guizhi Decoction () Inhibits Cholinergic Transdifferentiation by Regulating Imbalance of NGF and LIF in Salt-Sensitive Hypertensive Heart Failure Rats.

Objective: To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction () on sympathetic remodeling by inhibiting cholinergic transdifferentiation.

Methods: SS-13 and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13 group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle.

Functionalized Asymmetric Bola-Type Amphiphiles for Efficient Gene and Drug Delivery.

The studies of bolaamphiphile-based nanoparticles as delivery vectors are still rudimentary and under development. In this study, several asymmetric bolaamphiphiles containing lysine and another moiety with special functions, such as pH-sensitive or cell-targeting property, were designed and synthesized. The potentials of these bolaamphiphile-based nanoparticles as versatile vectors for both nucleic acids and chemical drugs were studied.

Cross-linked polymers with fluorinated bridges for efficient gene delivery.

A new strategy for the construction of fluorinated cationic polymers for gene delivery was introduced. The fluorinated polymers were synthesized by crosslinking low molecular weight PEI with diols containing various lengths of perfluoroalkyl chains via epoxide ring-opening polymerization. Such a study presents the first example of polymeric gene vectors with fluorination on the polymer backbone but not on the side chains.

Stretch force guides finger-like pattern of bone formation in suture.

Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown.

Amphiphilic polymers formed from ring-opening polymerization: a strategy for the enhancement of gene delivery.

Cationic liposomes and polymers are both important candidates for use as non-viral gene vectors. However, both of them have special shortcomings and application limits. This work is devoted to the combination of advantages of liposomes and polymers.

Structure-activity relationship studies of symmetrical cationic bolasomes as non-viral gene vectors.

Compared to traditional cationic lipids, bola-type lipids have received much less attention despite their advantages including the ability to form more stable and regular-shaped liposomes. In this report, a series of novel symmetric cationic bolalipids based on lysine or cyclen headgroups were designed and synthesized. Structure-activity relationships including the effect of the hydrophobic chain length and cationic headgroup on liposome formation, DNA binding, the physical property of bolasomes, and gene transfection were systematically studied.

Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of linking group structures.

The gene transfection efficiency (TE) of cationic lipids is largely influenced by the lipid structure. Six novel 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based cationic lipids L1-L6, which contain double oleyl as hydrophobic tails, were designed and synthesized. The difference between these lipids is their diverse backbone.

Inhibition of bleomycin-induced pulmonary fibrosis by bone marrow-derived mesenchymal stem cells might be mediated by decreasing MMP9, TIMP-1, INF-γ and TGF-β.

The study was aimed to investigate the mechanism and administration timing of bone marrow-derived mesenchymal stem cells (BMSCs) in bleomycin (BLM)-induced pulmonary fibrosis mice. Thirty-six mice were divided into six groups: control group (saline), model group (intratracheal administration of BLM), day 1, day 3 and day 6 BMSCs treatment groups and hormone group (hydrocortisone after BLM treatment). BMSCs treatment groups received BMSCs at day 1, 3 or 6 following BLM treatment, respectively.

Expression of caveolin-1 is correlated with lung adenocarcinoma proliferation, migration, and invasion.

Both tumor suppressor and tumor promoter roles, which are dependent on the tumor type, have been described for caveolin-1 (CAV-1). Because CAV-1 can modulate cell signaling, we tested the hypothesis that it regulates lung adenocarcinoma cell proliferation and metastasis via modulation of epidermal growth factor receptor (EGFR) activity. The lung adenocarcinoma cell line, GLC-82, was transfected with pcDNA3.

Effect of thoracic epidural blockade on hypoxia-induced pulmonary arterial hypertension in rats.

Objectives: The present study was aimed to investigate the influence of thoracic epidural blockade on hypoxia-induced pulmonary hypertension in rats.

Materials And Methods: Forty eight Wistar rats were randomly divided into 4 equal groups, named normoxia hypoxia hypoxia/ ropivacaine and hypoxia/saline. Animals were placed in a hypoxia chamber and instrumented with epidural catheters at the thoracic level.

Cyclen-based cationic lipids containing a pH-sensitive moiety as gene delivery vectors.

A series of novel cationic lipids based on 1,4,7,10-tetrazacyclododecane (cyclen) with the imidazole group as the pH-sensitive moiety and various aliphatic long chains were designed and synthesized. Cationic liposomes were prepared by mixing the lipids and the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in an appropriate molar ratio. The liposomes showed good stability and could condense plasmid DNA into nanosized particles (∼100 to ∼250 nm) with a positive zeta-potential (+10-25 mV).

miR-99a suppresses the metastasis of human non-small cell lung cancer cells by targeting AKT1 signaling pathway.

MicroRNAs (miRNAs) play an important role in the development and progression of non-small cell lung cancer (NSCLC). Recently, several studies have shown that miR-99a is downregulated in various cancers, which can affect tumor initiation and maintenance. Herein, we found that miR-99a was downregulated in NSCLC tissues and suppressed tumor metastasis of NSCLC cells.

[Epidemic situation and prevention strategy of schistosomiasis in Ya' an City after Lushan Earthquake on April 20, 2013].

This paper analyzes the recently epidemic status of schistosomiasis, the change of natural and social factors, and field survey and evaluation data of schistosomiasis in Ya'an City after Lushan Earthquake on April 20, 2013, and proposes that it is necessary to strengthen the conventional schistosomiasis control measures, the control of exogenous infection sources, the control of Oncomelania hupensis snails and health education for ensuring no major epidemics after the disaster. This paper also recommends the direction and suggestions for future schistosomiasis control in Ya' an City.

Activation of AKT/ERK confers non-small cell lung cancer cells resistance to vinorelbine.

Vinorelbine is a semi-synthetic vinca-alkaloid approved for the treatment of non-small cell lung cancer (NSCLC). However, the lower objective response rate and higher adverse effects of vinorelbine hinder its wide use in treatment of advanced NSCLC. Therefore, it is of great interest to uncover the biomarkers for sensitivity of NSCLC cells to vinorelbine to allow the identification of patients most likely to benefit from vinorelbine-based chemotherapy and to improve the therapy.

Biotinylated cyclen-contained cationic lipids as non-viral gene delivery vectors.

A series of 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based cationic lipids, namely 5a-c bearing a biotin moiety and a variety of end groups (cholesterol, diosgenin, and α-tocopherol) via biodegradable carbamate bond linkage were prepared and applied as non-viral gene delivery vectors. The liposomes formed from 5 and dioleoylphosphatidylethanolamine could bind and condense plasmid DNA into nanoparticles with appropriate size and zeta potentials. All biotinylated cyclen cationic lipids showed higher cell viability than commercially available lipofectamine 2000 even at high N/P ratios, while their transfection efficiency was relatively lower.