Fluorinated triphenylamine silicon phthalocyanine nanoparticles with two-color imaging guided in vitro photodynamic therapy through lysosomal dysfunction.

Lysosome-targeting therapy has emerged as a promising strategy for combating drug-resistant tumors. However, the synthesis of nanodrugs to achieve efficient lysosome targeting remains a challenging task. In this study, a nanoparticle DSPE@TPA-FBPA-SiPc was developed for lysosome targeting therapy. The nanoparticle was prepared by loading 2-[4-(diphenylamino)-1-diphenicacid-1-carbobenzoxy-4-(1,1,1,3,3,3-hexafluoropropane-4-phenoxy) silicon phthalocyanine (TPA-FBPA-SiPc) into 1,2-distearoyl-sn­glycero-3-phosphoethanolamine-N-[succinyl(polyethyleneglycol)-2000] (DSPE). DSPE@TPA-FBPA-SiPc demonstrated remarkable capabilities such as two-color imaging, lysosome targeting and in vitro photodynamic therapy functions. The results revealed that DSPE@TPA-FBPA-SiPc efficiently accumulated in lysosomes, leading to generation of a high amount of reactive oxygen species upon irradiation. This induced apoptosis in MCF-7 cells by disrupting lysosomal function. Consequently, DSPE@TPA-FBPA-SiPc holds great potential as a photosensitizer for photodynamic therapy, utilizing the lysosomal-mediated cell death pathway.

Ethanol mediates the interaction between Caenorhabditis elegans and the nematophagous fungus Purpureocillium lavendulum.

Accurately recognizing pathogens by the host is vital for initiating appropriate immune response against infecting microorganisms. Caenorhabditis elegans has no known receptor to recognize pathogen-associated molecular pattern. However, recent studies showed that nematodes have a strong specificity for transcriptomes infected by different pathogens, indicating that they can identify different pathogenic microorganisms. However, the mechanism(s) for such specificity remains largely unknown. In this study, we showed that the nematophagous fungus Purpureocillium lavendulum can infect the intestinal tract of the nematode C. elegans and the infection led to the accumulation of reactive oxygen species (ROS) in the infected intestinal tract, which suppressed fungal growth. Co-transcriptional analysis revealed that fungal genes related to anaerobic respiration and ethanol production were up-regulated during infection. Meanwhile, the ethanol dehydrogenase Sodh-1 in C. elegans was also up-regulated. Together, these results suggested that the infecting fungi encounter hypoxia stress in the nematode gut and that ethanol may play a role in the host-pathogen interaction. Ethanol production in vitro during fungal cultivation in hypoxia conditions was confirmed by gas chromatography-mass spectrometry. Direct treatment of C. elegans with ethanol elevated the sodh-1 expression and ROS accumulation while repressing a series of immunity genes that were also repressed during fungal infection. Mutation of sodh-1 in C. elegans blocked ROS accumulation and increased the nematode's susceptibility to fungal infection. Our study revealed a new recognition and antifungal mechanism in C. elegans. The novel mechanism of ethanol-mediated interaction between the fungus and nematode provides new insights into fungal pathogenesis and for developing alternative biocontrol of pathogenic nematodes by nematophagous fungi. IMPORTANCE Nematodes are among the most abundant animals on our planet. Many of them are parasites in animals and plants and cause human and animal health problems as well as agricultural losses. Studying the interaction of nematodes and their microbial pathogens is of great importance for the biocontrol of animal and plant parasitic nematodes. In this study, we found that the model nematode Caenorhabditis elegans can recognize its fungal pathogen, the nematophagous fungus Purpureocillium lavendulum, through fungal-produced ethanol. Then the nematode elevated the reactive oxygen species production in the gut to inhibit fungal growth in an ethanol dehydrogenase-dependent manner. With this mechanism, novel biocontrol strategies may be developed targeting the ethanol receptor or metabolic pathway of nematodes. Meanwhile, as a volatile organic compound, ethanol should be taken seriously as a vector molecule in the microbial-host interaction in nature.

Protective effects of nizofenone administration on the cognitive impairments induced by chronic restraint stress in mice.

The present study was aimed to investigate the effects of nizofenone administration on the chronic restraint stress-induced cognitive impairments in mice. Adult male mice were randomized into five groups: control group, nizofenone control group, chronic restraint stress group, and nizofenone treatment groups (3.0mg/kg and 9.0mg/kg). The changes of cognitive performances were examined by Morris water maze (MWM), open field and step-through tests. Our results showed that the cognitive performances in CRS group were markedly deteriorated, accompanied by noticeable alterations in oxidative parameters, acetylcholinesterase activity and catecholamines levels in the hippocampus and the prefrontal cortex. These changes could be reversed by nizofenone treatment. Moreover, CRS group showed higher corticosterone levels and lower catecholamines levels in the serum, which were reversed in the nizofenone treatment groups. Collectively, the present results suggested the potential of nizofenone in attenuating the CRS-induced cognitive impairments.

Protective effect of L-citrulline against acute gastric mucosal lesions induced by ischemia-reperfusion in rats.

The present study investigated the protective effect of L-citrulline on gastric mucosal injury induced by ischemia-reperfusion (IR) in rats. Under anesthesia, the celiac artery was clamped for 30 min, and then the clamp was removed for 60 min reperfusion. Sixty minutes before ischemia, L-citrulline was administered intragastrically at doses of 300, 600, and 900 mg/kg. After the experiment, the stomachs were removed for biochemical and histological examinations. Pretreatment with L-citrulline (300, 600, and 900 mg/kg) significantly ameliorated the gastric damage caused by IR. Moreover, L-citrulline prevented the production of lipid peroxidation and inhibited the increase of myeloperoxidase activity. The elevation in total nitric oxide synthase (NOS) activity, inducible NOS activity, and inducible NOS protein expression as well as the decrease in constitutive NOS activity and gastric mucus level in the gastric mucosa induced by IR were significantly prevented. However, the protective effect mediated by L-citrulline was significantly antagonized by coadministration of L-nitroarginine methyl ester (10 mg/kg, s.c.). These results suggest that part of the mechanism of gastric protection by L-citrulline might be through inhibiting neutrophil infiltration and preserving gastric mucus synthesis and secretion in rats, functions that are closely related to the maintenance of constitutive NOS activity.

Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice.

L-theanine (γ-glutamylethylamide), an amino acid component of green tea, has been shown to reduce mental and physical stress, and to improve memory function. In this study, the antidepressant effect of L-theanine was investigated in mice using the forced swim test, tail suspension test, open-field test and reserpine test. L-theanine produced an antidepressant-like effect, since the administration of L-theanine at doses of 1, 4 and 20 mg/kg for 10 successive days significantly reduced the immobility time in both the forced swim test and tail suspension test, compared with the control group, without accompanying changes in ambulation in the open-field test. Moreover, L-theanine significantly antagonized reserpine-induced ptosis and hypothermia. Taken together, these results indicate that L-theanine possessed an antidepressant-like effect in mice, which may be mediated by the central monoaminergic neurotransmitter system.

[The early postoperative complications and cost-effectiveness analysis of non-penetrating trabecular surgery in patients with primary open angle glaucoma].

OBJECTIVE: To compare the early postoperative complications of non-penetrating trabecular surgery (NPTS) and modified trabeculectomy (MT) in patients with primary open angle glaucoma, and to analyze the cost-effectiveness of NPTS to prevent adverse events as well. METHODS: One hundred and forty seven consecutive cases (215 eyes) with primary open angle glaucoma from the glaucoma division, Zhongshan Ophthalmic Center, were involved. One hundred and four eyes underwent NPTS; while 111 eyes underwent MT. Visual acuity, intraocular pressure and complications occurred while staying in the hospital, were recorded. Number of need to treat (NNT) was used to analyze the cost-effective for NPTS. RESULTS: (1) Visual acuity decrease over 2 lines occurred in 25 eyes (24.0%) in NPTS group and 26 eyes (23.4%) in MT group. The difference of visual changes between these two groups was not statistically significant (P > 0.05). (2) One day after the operation, hypotension [IOP less or equal to 5 mm Hg (1 mm Hg = 0.133 kPa)] occurred in 39 eyes in NPTS group (38.2%), and 10 eyes in MT group (9.2%). The difference was significant (P < 0.01). On the day of discharge, the incidence of hypotension was 27.5% in NPTS group and 17.3% in MT group, respectively. The difference was still significant (P < 0.05). (3) Hyphema was found in 20 eyes (19.2%) in NPTS group and ten eyes (9.0%) in MT group. In either group, a surgical procedure was needed in two eyes to evacuate the blood. (4) Two eyes of grade II degrees and five eyes of grade I degrees shallow chamber were found in NPTS group. Five eyes of grade II degrees and five eyes of grade I shallow chamber were found in MT group. The difference of incidence of shallow chamber between these two groups was not statistically significant (P > 0.05). (5) Other complications: In the NPTS group, trabeculo-descemetic membrane rupture occurred in one eye, pupil dilated to 7 mm observed in six eyes; in the MT group, acute elevated IOP occurred in one eye, peripheral anterior synechia at inner incision occurred in one eye, hypotensive macular edema occurred in one eye. (6) The absolute risk ratio (ARR) of NPTS for adverse event was 3.0%, (NNT = 33.2), it costs additional RMB yen 116, 100 for preventing one adverse event. For serious adverse event, ARR = 1.8% (NNT = 55.5), and it costs additional RMB yen 194, 000 to prevent one serious adverse event. CONCLUSIONS: Although the NPTS may reduce the incidence of serious adverse event in comparing with MT, the cost of NPTS is very high, therefore, it is not an optimal procedure in China. Ophthalmologists in the general hospital should familiar with the MT procedure to save the medical expenses.