Hypericin-photodynamic therapy inhibits the growth of adult T-cell leukemia cells through induction of apoptosis and suppression of viral transcription.

BACKGROUND: Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). ATL carries a poor prognosis due to chemotherapy resistance. Thus, it is urgent to develop new treatment strategies. Hypericin (HY) is a new-type of photosensitizer in the context of photodynamic therapy (PDT) due to its excellent photosensitizing properties and anti-tumor activities. RESULTS: In the present study, we investigated the efficacy of hypericin in ATL cells. Clinically achievable concentrations of hypericin in association with PDT induced the inhibition of cell proliferation in ATL cell lines with minimal effect on peripheral blood CD4+ T lymphocytes. Moreover, hypericin-PDT treatment caused apoptosis and G2/M phase cell cycle arrest in leukemic cells. Western blot analyses revealed that hypericin-PDT treatment resulted in downregulation of Bcl-2 and enhanced the expression of Bad, cytochrome C, and AIF. Cleavage of caspases-3/-7/-9/-8, Bid, and PARP was increased in hypericin-PDT-treated ATL cells. In a luciferase assay, hypericin-PDT treatment was able to activate the promoter activity of Bax and p53, resulting in enhanced expression of Bax and p53 proteins. Finally, hypericin-PDT treatment suppressed the expression of viral protein HBZ and Tax by blocking the promoter activity via HTLV-1 5'LTR and 3'LTR. CONCLUSIONS: Our results revealed that hypericin-PDT is highly effective against ATL cells by induction of apoptosis and suppression of viral transcription. These studies highlight the promising use of hypericin-PDT as a targeted therapy for ATL.

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro.

BACKGROUND: Photodynamic therapy (PDT) is becoming a promising therapeutic modality for hematological malignancies. Hypericin is a natural photosensitizer possessing anti-depressant, anti-virus and anti-cancer activities. The present study was designed to explore the effect and mechanism of hypericin-mediated PDT on the mouse multiple myeloma (MM) cells in vitro. METHODS: The mouse myeloma SP2/0 cells were incubed with different concentrations of hypericin and then illuminated with different light doses. The inhibitory effect of hypericin-mediated PDT on tumor cell proliferation was assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. The apoptosis related morphological changes of SP2/0 cells were observed by microscopy. The biochemical hallmarks of apoptosis such as DNA fragments, mitochondrial membrane potential changes were assessed. The expression of apoptosis related proteins were investigated by western blotting. RESULTS: Hypericin-mediated PDT induced the proliferation inhibition and apoptosis of tumor cells in a dose dependent manner. Tumor cells showed obvious morphological changes of apoptosis and necrosis and DNA fragmentation after treated by hypericin mediated PDT (0.025 ~ 0.05 µM). The mitochondria membrane potential in SP2/0 cells was decreased significantly after incubated with the 0.025 µM and 0.5 µM hypericin (P < 0.05). The expression level of caspase-3 was decreased, while caspase activity was elevated with the increasing drug dosage. The apoptosis of SP2/0 cells was blocked by a pan-caspase inhibitor Z-VAD-FMK and caspase-3 inhibitor Ac-DEVD-CHO. CONCLUSION: Hypericin-mediated PDT induced apoptosis mainly dependent on caspase related pathways. Hypericin-mediated PDT may be a potential and alternative therapy for MM.

Highly luminescent N-doped carbon quantum dots as an effective multifunctional fluorescence sensing platform.

The doping of carbon quantum dots with nitrogen provides a promising direction to improve fluorescence performance and broaden their applications in sensing systems. Herein we report a one-pot solvothermal synthesis of N-doped carbon quantum dots (NCQDs) and the synthesis of a series of NCQDs with different nitrogen contents. The as-prepared NCQDs were compared with carbon quantum dots (CQDs); the introduction of nitrogen atoms largely increased the quantum yield of NCQDs and highest emission efficiency is up to 36.3 %. The fluorescence enhancement may originate from more polyaromatic structures induced by incorporated nitrogen atoms and protonation of nitrogen atoms on dots. It was found that NCQDs can act as a multifunctional fluorescence sensing platform because they can be used to detect pH values, Ag(I), and Fe(III) in aqueous solution. The fluorescence intensity of NCQDs is inversely proportional to pH values across a broad range from 5.0 to 13.5, which indicates that NCQDs can be devised as an effective pH indicator. Selective detection of Ag(I) and Fe(III) was achieved based on their distinctive fluorescence influence because Ag(I) can significantly enhance the fluorescence whereas Fe(III) can greatly quench the fluorescence. The quantitative determination of Ag(I) can be accomplished with NCQDs by using the linear relationship between fluorescence intensity of NCQDs and concentration of Ag(I). The sensitive detection of H2O2 was developed by taking advantage of the distinct quenching ability of Fe(III) and Fe(II) toward the fluorescence of NCQDs. Cellular toxicity test showed NCQDs still retain low toxicity to cells despite the introduction of a great deal of nitrogen atoms. Moreover, bioimaging experiments demonstrated that NCQDs have stronger resistance to photobleaching than CQDs and more excellent fluorescence labeling performance.

[Essential oil from Artemisia lavandulaefolia induces apoptosis and necrosis of HeLa cells].

OBJECTIVE: To investigate the effects of Artemisia lavandulaefolia essential oil on apoptosis and necrosis of HeLa cells. METHODS: Cell viability was assayed using MTT method. The morphological and structure alterations in HeLa cells were observed by microscopy. Furthermore, cell apoptosis was measured by DNA Ladder and flow cytometry. DNA damage was measured by comet assay, and the protein expression was examined by Western blot analysis. RESULTS: MTT assay displayed essential oil from Artemisia lavandulaefolia could inhibit the proliferation of HeLa cells in a dose-dependent manner. After treated with essential oil of Artemisia lavadulaefolia for 24 h, HeLa cells in 100 and 200 microg/mL experiment groups exhibited the typical morphology changes of undergoing apoptosis, such as cell shrinkage and nucleus chromatin condensed. However, the cells in the 400 microg/mL group showed the necrotic morphology changes including cytomembrane rupture and cytoplasm spillover. In addition, DNA Ladder could be demonstrated by DNA electrophoresis in each experiment group. Apoptosis peak was also evident in flow cytometry in each experiment group. After treating the HeLa cells with essential oil of Artemisia lavadulaefolia for 6 h, comet tail was detected by comet assay. Moreover, western blotting analysis showed that caspase-3 was activated and the cleavage of PARP was inactivated. CONCLUSION: Essential oil from Artemisia lavadulaefolia can inhibit the proliferation of HeLa cells in vitro. Low concentration of essential oil from Artemisia lavadulaefolia can induce apoptosis, whereas high concentration of the compounds result in necrosis of HeLa cells. And,the mechanism may be related to the caspase-3-mediated-PARP apoptotic signal pathway.

Dietary restriction reduces blood lipids and ameliorates liver function of mice with hyperlipidemia.

Dietary restriction (DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet (HFD) (34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group (P<0.05 or P<0.01), so did alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels and the ratio of LDL-C/HDL-C in the DR50% group (P<0.05 or P<0.01). Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1 (SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma (PPARγ) in adipose (P<0.05 or P<0.01). The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.

[Effects of soybean phospholipids on learning and memory ability and contents of lipids in mice's brain].

OBJECTIVE: To study the effects of soybean phospholipids on learning and memory abilities and contents of protein and lipids in brain of mice. METHODS: Mice were randomly divided into four groups: low dose (2.5 g/kg), middle dose(5.0 g/kg) and high dose (10.0 g/kg) of soybean Phospholipids in diet and control group (distilled water). The mice were fed with soybean phospholipids everyday while control groups were fed with distilled water for 30 days. After learning and memory abilities were measured, the mice were killed and contents of protein, fatty acids and phospholipids in brain of mice were determined. RESULTS: The learning and memory abilities of mice fed with middle and high dose of soybean Phospholipids were improved obviously(P < 0.05), while memory abilities of low dose's mice were stronger than that of control(P < 0.05). (2) The brain weight v.8 body weight of those in three doses' group was obviously increased, and the protein content in brain was significantly higher compared with control(P < 0.05). (3) The contents of linoleic acid(C18: 2), linolenic acid(C18: 3) and ratio of polyunsaturated fatty acids(PUFA) to total fatty acids (TFA) obviously increased (P < 0.05). In brain of high dose mice, there was obvious change in the content of linolenic acid(C18: 3) in middle's (P < 0.05). (4) The contents of phosphatidylcholine (PS) phosphatidylethanolamine (PE), Phosphatidylcholine (PC) and phospholipids (PL) obviously increase (P < 0.05), while ratio of SM to PC was decreased significantly in brain of high dose mice(P < 0.05). The contents of PS, PC and PL were increased obviously(P < 0.05). CONCLUSION: Soybean phospholipids may increase contents of protein, PUFA and PL in brain of mice and improve learning and memory abilities of mice effectively in a dose-response manner.

[Effects of soybean phospholipid on the content of malondialdehyde and lipofuscin in heart, liver and spleen in mice].

In order to observe the effects of soybean phospholipids on the SOD activity in liver and the content of malondialdehyde and lipofuscin in heart, liver and spleen in mice, forty male mice were divided into 4 groups. Experimental mice were fed with different doses of soybean phospholipids (2.5, 5 and 10 g/kg BW) and the control mice were fed with normal saline by tube feeding for 18 days. After that, the SOD activity in liver and the content of malondialdehyde and lipofuscin in heart, liver and spleen were measured. The results showed that the three doses of soybean phospholipid could significantly increased the SOD activity of liver (P < 0.05), and also could remarkably decrease the malondialdehyde content of in heart(P < 0.01) and in liver (P < 0.05). The soybean phospholipid at dose of 2.5 g/kg BW could significantly decrease the malondialdehyde content of in spleen(P < 0.05). But the three doses of soybean phospholipid did not obviously affect the content of lipofusin in liver, heart and spleen. The study indicated that the soybean phospholipid was effective on the inhibition of lipid peroxide.

[Effects of the extract from bergamot and boxthorn on the delay of skin aging and hair growth in mice].

OBJECTIVE: To study the effects of the extract from bergamot and boxthorn on the skin and the hair growth in mice. METHOD: The skin on the back of mice was shaved topically and smeared with bergamot and boxthorn extract for 42 days. Then the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) and collagen in the mice were measured. The growth of hair was also observed. RESULT: Compared with control group, the extract from bergamot and boxthorn obviously increased the activity of superoxide dismutase (P < 0.05) and the content of collagen (P < 0.001), and decreased the content of malondialdehyde (P < 0.05) in the skin of mice. It also significantly promoted the growth of hair (P < 0.001). CONCLUSION: The extract from bergamot and boxthorn plays an active role in skin and the promotion of hair growth.

Effects of external qi of qigong with opposing intentions on proliferation of Escherichia coli.

BACKGROUND: The existence and characteristics of external qi (EQ) in qigong therapy has long been subject to scientific debate and rigorous examination. The therapist's intent has played an important role in many studies. This study investigates the effect of EQ with opposing intentions on the proliferation of Escherichia coli. METHODS: We performed two studies with the same design. In study 1, 75 5-mL tubes containing test samples (3 mL each) were randomly divided into three groups: control, promoted, and inhibited group (25 each). In study 2, three 96-well plates with test samples (200 microL each) were randomly designated as control, promoted, or inhibited. Test samples were placed 60 cm apart on a bench with control in the middle. A qigong therapist performed EQ with either promoting or killing intent for 15 minutes each on the treatment groups. After incubation for 24 hours, optical density of the E. coli samples was measured at 600 nm (OD(600)). RESULTS: In the initial experiment of both studies, the OD(600) value of the promoted group was significantly higher than that of control (p < 0.05), while the OD(600) value of the inhibited group was significantly lower than that of the control group (p < 0.01), suggesting that the healer's intent played a critical role in the effects of EQ on E.coli proliferation. However, subsequent experiments did not replicate the initial finding in either study and showed a pattern of declining effect. CONCLUSION: A healer's intent may affect the proliferation of microbes with specificity and directivity, so future studies of bioenergy healing should take the role of intention into consideration. The circumstances surrounding replication of the results in such biofield studies need further exploration.