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Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8 + T cells and immunomodulatory roles mediated by CD4 + T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4 + T cells were significantly upregulated in breast cancer patients compared to healthy controls. The IL-9-expressing Th9 cells were enriched in the CCR4 − CCR6 − CXCR3 − subset. Upon TCR stimulation, this subset also presented potent IL-10 and IL-21 expression in addition to IL-9 expression. CCR4 − CCR6 − CXCR3 − CD4 + T cells also assisted in the killing of autologous tumor cells by CD8 + T cells, but did not initiate cytotoxicity by themselves. This enhancement in CD8 + T cell-mediated cytotoxicity was dependent on IL-9 as well as on IL-21. Interestingly, the tumor-infiltrating Th9 cells presented comparable IL-9, reduced IL-10, and elevated IL-21 expression compared with their counterparts in the peripheral blood. Together, these results demonstrated that IL-9-expressing Th9 cells were upregulated in breast cancer patients and potentially possessed antitumor roles by enhancing CD8 + T cell-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance In traditional Chinese medicine (TCM), Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases. Recently, Huangkui capsule (HKC), a Chinese patent medicine extracted from AM, has been widely applied to the clinical therapy of renal fibrosis in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain ambiguous. The goal of this study is to expound the mechanism in vivo of HKC in order to deepen the understanding of its clinical effects, by using the approaches of contrasting the dose-effects of HKC on oxidative stress (OS) in the kidney compared to α-lipoic acid (LA), and then demonstrating whether and how anti-oxidative properties of HKC or LA might be beneficial for the treatment of renal fibrosis in vivo. Materials and methods Thirty-three rats were divided into 5 groups, a Sham group, a Vehicle group, a L-HKC group, a H-HKC group and a LA group. The different doses of HKC, LA and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with streptozotocin (STZ) intraperitoneal injections. Rat's general status, biochemical parameters, renal histological changes and OS indicators, as well as the key protein expressions in p38 mitogen-activated protein kinase (p38MAPK)/serine-threonine kinase (Akt) signaling pathways and downstream cytokines including transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α were examined, respectively. Results HKC and LA ameliorated body weight, kidney weight, urinary albumin and renal function including blood urea nitrogen and serum uric acid, attenuated renal fibrosis including the cell numbers and extracellular matrix rate in glomerulus, and controlled OS indicators including malondialdehyde, total superoxide dismutase, 8-hydroxy-2′-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase 4, but did not lower blood glucose in DN model rats. Among them, the anti-renal fibrosis effect of H-HKC was better than that of LA. In addition, HKC simultaneously down-regulated the protein expressions of phosphorylated p38MAPK, phosphorylated Akt (p-Akt), TGF-β1 and TNF-α in the kidney of DN model rats, unlike HKC, LA only down-regulated p-Akt and TNF-α protein expressions. Conclusion We have demonstrated that HKC, similar to LA, is renoprotective via attenuating OS and renal fibrosis in the DN rat model. The potential mechanisms by which HKC and LA exert their therapeutic effects in vivo are respectively through down-regulating the activation of p38MAPK and/or Akt pathways as well as the expressions of TGF-β1 and/or TNF-α in the kidney. Our findings thus provide the useful information about a clinical combination of HKC and LA in early DN patients. [ABSTRACT FROM AUTHOR]

An efficient one-pot reaction for the synthesis of oxoaporphine alkaloids has been developed. Twenty-three compounds of oxoaporphine alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, 4B displayed the most potent activity with an IC 50 value of 0.5 μM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by −NO 2 significantly enhanced the anticancer activity. Mechanism studies indicated that 4 and 4B induced cell cycle arrest at G2/M phase; in contrast, 4V induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of caspase-3/9, were observed in T-24 cells after exposure to compounds 4 , 4B and 4V , suggesting that the mitochondrial pathway was involved in the induced apoptosis. Moreover, compound 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24. [Display omitted] • One-pot reaction for synthesis of oxoaporphine alkaloids was developed. • A series of oxoaporphine alkaloids were synthesized. • 4B induced DNA damage, and caused significant G2/M cell cycle arrest. • 4B induced caspase-3/9-dependent apoptosis through mitochondrial dysfunction. • 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24. [ABSTRACT FROM AUTHOR]

In addition to being associated with energy supply, lipid droplets (LDs) play vital roles in many other important physiological and some pathological processes. Fluorescent probes are useful tools for studying the biological functions of LDs. In this study, we develop three new highly fluorescent LD-specific bioprobes, which can be excited by one- and two-photon, with favorable biocompatibility. They have little crosstalk with some commonly used commercially-available green- and red-emissive probes, such as BODIPY 493/503, MitoTracker Red CMXRos (MTR) and LysoTracker Red DND-99 (LTR), thus allowing the simultaneous multicolor imaging. Notably, one of the probes, BIP-1 , has superior photostability and allows excellent 3D imaging of cellular LDs. BIP-1 can be used to monitor the number and morphological changes of LDs, and the interactions of LDs with other organelles (e.g. mitochondria) under specific physiological conditions (e.g. starvation). Overall, BIP-1 is a promising alternative fluorescent bioprobe for live-cell LD-specific imaging and long-term tracking during LD-related research. Image 1 • A series of lipid droplet probes were developed. • The probes can light up lipid droplets with specificity. • The probes have good biocompatibility and excellent photostability. • The probes allow 3D imaging and can monitor the metabolism of lipid droplets. [ABSTRACT FROM AUTHOR]