Establishment and characterization of immortalized human breast cancer cell lines from breast cancer patient-derived xenografts (PDX).

The application of patient-derived xenografts (PDX) in drug screening and testing is a costly and time-consuming endeavor. While cell lines permit extensive mechanistic studies, many human breast cancer cell lines lack patient characteristics and clinical treatment information. Establishing cell lines that retain patient's genetic and drug response information would enable greater drug screening and mechanistic studies.

A combination of morphological and photosynthetic functional traits maintains the vertical distribution of bryophytes in a subtropical cloud forest.

Premise: The distribution and performance of bryophyte species vary with vertical gradients, as a result of changes in environmental factors, especially light. However, the morphological and physiological drivers of bryophyte distribution along forest vertical gradients are poorly understood.

Methods: For 18 species of mosses and liverworts distributed among three vertical microhabitats (ground, tree trunk, and branch, variance in 28 morphological and photosynthetic functional traits was comparatively analyzed among the microhabitats and bryophyte life-forms in a subtropical cloud forest in Ailao Mountain, Yunnan, southwestern China.

Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria-Targeted Fluorescent Organic Arsenical in vitro and in vivo.

Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family-dependent apoptosis.

LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical.

Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling.

The novel function of tumor protein D54 in regulating pyruvate dehydrogenase and metformin cytotoxicity in breast cancer.

Background: The role of tumor protein D54 in breast cancer has not been studied and its function in breast cancer remains unclear. In our previous pharmacogenomic studies using lymphoblastoid cell line (LCL), this protein has been identified to affect metformin response. Although metformin has been widely studied as a prophylactic and chemotherapeutic drug, there is still a lack of biomarkers predicting the response to metformin in breast cancer.

A mitochondria-targeted organic arsenical accelerates mitochondrial metabolic disorder and function injury.

Considering the vital role of mitochondria in the anti-cancer mechanism of organic arsenical, the mitochondria-targeted precursor PDT-PAO-TPP was designed and synthesized. PDT-PAO-TPP, as a delocalization lipophilic cation (DLCs) which mainly accumulated in mitochondria, contributed to improve anti-cancer efficacy and selectivity towards NB4 cells. In detail, PDT-PAO-TPP inhibited the activity of PDHC resulting in the suppression of ATP synthesis and thermogenesis disorder.

Mitochondrial toxicity of organic arsenicals: membrane permeability transition pore opening and respiratory dysfunction.

In order to clarify the mitochondrial toxicity mechanism of the organic arsenical (2-methoxy-4-(((4-(oxoarsanyl) phenyl) imino) methyl) phenol), research was carried out at the sub-cell level based on the previous finding that the compound can damage the mitochondria by triggering a burst of ROS. After investigating its influence on isolated mitochondria , it was demonstrated that a high dose of with short-term exposure can induce mitochondrial swelling, decrease the membrane potential, enhance the permeability of H and K, and induce membrane lipid peroxidation, indicating that it can result in an MPT process in a ROS-mediated and Ca-independent manner. Additionally, MPT was also aggravated as a result of impairment of the membrane integrity and membrane fluidity.

Organic arsenicals target thioredoxin reductase followed by oxidative stress and mitochondrial dysfunction resulting in apoptosis.

Considering the vital role of cellular redox state, more and more researches focus on the design of drugs targeting thioredoxin reductase (TrxR), an important enzyme in maintaining the balance of cellular redox. Here two organic arsenicals, 2-(((4-(1,3,2-dithiarsinan-2-yl) phenyl) imino) methyl) phenol (PIM-PAO-PDT) and N-(4-(1,3,2-dithiarsinan-2-yl) phenyl)-2-hydroxybenzamide (PAM-PAO-PDT), bearing the S-As-S chemical scaffold and different linking groups have been synthesized, and both of them show the better inhibitory activity and selectivity towards HL-60 cells. Importantly, it is illustrated that they can target TrxR selectively and inhibit its activity via the disturbance for Cys83 and Cys88 located in conserved active sites.

Uncoupling Effect of F16 Is Responsible for Its Mitochondrial Toxicity and Anticancer Activity.

As a novel delocalized lipophilic cation, F16 selectively accumulates in mitochondria of carcinoma cells and shows a broad spectrum of antiproliferative action towards cancer cell lines. In order to reveal the mode of action and molecular mechanism of F16 inducing cytotoxicity, we investigated the effects of F16 on cancer cells and isolated mitochondria relative to its precursor compound (E)-3-(2-(pyridine-4yl)vinyl)-1 H-indole (PVI), which has a similar structure without positive charge. It was found that PVI did not accumulate in mitochondria, and exhibited lower cytotoxicity compared to F16.

A lysosome-targeted fluorescent sensor for the detection of glutathione in cells with an extremely fast response.

A highly sensitive and selective Rhodamine B-based fluorescent sensor, RhB-1, for glutathione (GSH) was easily synthesized. An extremely fast detection response time of 10 s, which is the fastest one ever reported, is achieved in aqueous solutions over a wide pH range with large enhancement of emission intensity. The sensor detects GSH in cells and selectively accumulates in lysosomes.

Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals.

Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7.

Resonance energy transfer, pH-induced folded states and the molecular interaction of human serum albumin and icariin.

Icariin is a flavonol glycoside with a wide range of pharmacological and biological activities. The pharmacological and biological functions of flavonoid compounds mainly originate from their binding to proteins. The mode of interaction of icariin with human serum albumin (HSA) has been characterized by fluorescence spectroscopy and far- and near-UV circular dichroism (CD) spectroscopy under different pH conditions.

Hypomethylation and overexpression of ITGAL (CD11a) in CD4(+) T cells in systemic sclerosis.

Background: The pathogenesis and etiology of systemic sclerosis (SSc) are complex and poorly understood. To date, several studies have demonstrated that the activation of the immune system undoubtedly plays a pivotal role in SSc pathogenesis. Activated immune effector T cells contribute to the release of various pro-inflammatory cytokines and drive the SSc-specific autoantibody responses.

Exploring the site-selective binding of jatrorrhizine to human serum albumin: spectroscopic and molecular modeling approaches.

This paper exploring the site-selective binding of jatrorrhizine to human serum albumin (HSA) under physiological conditions (pH=7.4). The investigation was carried out using fluorescence spectroscopy, UV-vis spectroscopy, and molecular modeling.

Biophysical studies on the interactions of jatrorrhizine with bovine serum albumin by spectroscopic and molecular modeling methods.

The interaction between jatrorrhizine (JAT) and bovine serum albumin (BSA) has been studied. The studies were carried out in a buffer medium at pH 7.4 using fluorescence spectroscopy, UV-vis spectroscopy, and molecular modeling methods.

Comprehensive study of the interaction between a potential antiprion cationic porphyrin and human prion protein at different pH by using multiple spectroscopic methods.

Cationic porphyrins are potential antiprion drugs; however, the action mechanisms remain poorly understood. Herein, the interaction between a cationic porphyrin and recombinant human prion protein (rPrP(C)) was comprehensively studied by using surface plasmon resonance (SPR), fluorescence, resonance light scattering (RLS), and circular dichroism (CD) spectroscopy. The experimental results showed that the interaction between the cationic porphyrin and rPrP(C) was pH dependent.