Genomic instability-associated two-miRNA signature as a novel prognostic biomarker in breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of cancer-associated deaths among women. However, there is a lack of accurate prognostic biomarkers for BC. In the present study, we aimed to identify a genomic instability (GI)-associated microRNA signature as a novel potential prognostic biomarker in BC. METHODS: We performed an integrative analysis to investigate the relationship between GI and BC and identify GI-associated microRNAs (miRNAs). Subsequently, we conducted a discovery and validation study using multicenter cohorts. The GI-associated miRNA signature was developed in the discovery cohort and independently validated in internal and external cohorts. RESULTS: GI-associated miRNAs expression in BC showed heterogeneity and was significantly correlated with BC prognosis. We identified a GI-associated two-miRNA signature (miR-105-5p and miR-767-5p), termed GI2miR, that stratified BC patients into high-risk and low-risk groups with significantly different clinical outcomes (log-rank p = 0.027) in The Cancer Genome Atlas (TCGA) discovery cohort (n = 763). The prognostic value of GI2miR was further validated in internal TCGA validation cohort (n = 253) (log-rank p = 0.035) and independent GSE22216 cohort (n = 210) (log-rank p = 0.036). The GI2miR demonstrated independent prognostic value in multivariate Cox proportional hazard regression analyses and stratification analysis. CONCLUSIONS: We have developed a novel prognostic signature based on GI-associated two miRNAs for BC, which may lay the foundation for BC to improve prognosis prediction.

Synthesis and Biological Evaluation of Methoxypolyethylene-Glycol-Substituted Abiraterone Derivatives as Potential Antiprostate Cancer Agents.

Globally, prostate cancer is the most commonly diagnosed tumor and a cause of death in older men. Abiraterone, an orally administered irreversible CYP17 inhibitor, is employed to treat prostate cancer. However, abiraterone has several clinical limitations, such as poor water solubility, low dissolution rate, low bioavailability, and toxic side effects in the liver and kidney. Therefore, there is a need to identify high-efficiency and low-toxicity water-soluble abiraterone derivatives. In this work, we aimed to design and synthesize a series of abiraterone derivatives by methoxypoly(ethylene glycol) (mPEG) modification. Their antitumor activities and toxicology were analyzed in vitro and in vivo. The most potent compound, 2e, retained the principle of action on the CYP17 enzyme target and significantly improved the abiraterone water solubility, cell permeability, and blood safety. No significant abnormalities were observed in toxicology. mPEG-modification significantly improved abiraterone's antitumor activity and efficiency while reducing the associated toxic effects. The finding will provide a theoretical basis for future clinical application of mPEG-modified abiraterone.

Controlling the thermoelectric properties of organo-metallic coordination polymers through backbone geometry.

Poly(nickel-benzene-1,2,4,5-tetrakis(thiolate)) (Ni-btt), an organometallic coordination polymer (OMCP) characterized by the coordination between benzene-1,2,4,5-tetrakis(thiolate) (btt) and Ni2+ ions, has been recognized as a promising p-type thermoelectric material. In this study, we employed a constitutional isomer based on benzene-1,2,3,4-tetrakis(thiolate) (ibtt) to generate the corresponding isomeric polymer, poly(nickel-benzene-1,2,3,4-tetrakis(thiolate)) (Ni-ibtt). Comparative analysis of Ni-ibtt and Ni-btt reveals several common infrared (IR) and Raman features attributed to their similar square-planar nickel-sulfur (Ni-S) coordination. Nevertheless, these two polymer isomers exhibit substantially different backbone geometries. Ni-btt possesses a linear backbone, whereas Ni-ibtt exhibits a more undulating, zig-zag-like structure. Consequently, Ni-ibtt demonstrates slightly higher solubility and an increased bandgap in comparison to Ni-btt. The most noteworthy dissimilarity, however, manifests in their thermoelectric properties. While Ni-btt exhibits p-type behavior, Ni-ibtt demonstrates n-type carrier characteristics. This intriguing divergence prompted further investigation into the influence of OMCP backbone geometry on the electronic structure and, particularly, the thermoelectric properties of these materials.

Inhibition of the STAT3-EPHX2 axis promotes regression of ulcerative colitis by treatment with novel porphyrin derivative.

LD4, a novel porphyrin derivative, has attracted much attention for its excellent anti-inflammatory properties. It can promote the healing of colonic mucosa, reduce inflammatory response, regulate oxidative stress, and thus improve ulcerative colitis (UC) symptoms. However, the specific signaling pathways of LD4-PDT involved in UC have not been explored. The present study aimed to elucidate the effects of LD4 on UC and to investigate the underlying mechanisms both in vivo and in vitro. We classified and screened the LD4-PDT proteomic data to obtain key targets. Proteomic data revealed that EPHX2 and STAT3 are key targets of LD4-PDT for UC. Moreover, transcription factor STAT3 positively regulates the expression of EPHX2. Inhibiting EPHX2 can prevent the activation of NF-κB signaling pathway. Next, through pharmacological inhibition experiments, we confirmed that LD4-PDT can reduce intestinal inflammation by inhibiting STAT3-EPHX2 axis. However, by treating normal intestinal epithelial cells and colon cancer cells with TPPU and Stattic, our data confirmed that the STAT3-EPHX2 axis does not exist in colon cancer. In this study, we demonstrated that the transcription factor STAT3 can positively regulate the expression of EPHX2 in normal colon. LD4 can alleviate UC by inhibiting the STAT3-EPHX2 axis, but this axis does not exist in colon cancer. LD4-PDT may become a new and effective method for treating UC.

A Novel Paclitaxel Derivative for Triple-Negative Breast Cancer Chemotherapy.

Paclitaxel-triethylenetetramine hexaacetic acid conjugate (PTX-TTHA), a novel semi-synthetic taxane, is designed to improve the water solubility and cosolvent toxicity of paclitaxel in several aminopolycarboxylic acid groups. In this study, the in vitro and in vivo antitumor effects and mechanisms of PTX-TTHA against triple-negative breast cancer (TNBC) and its intravenous toxicity were evaluated. Results showed the water solubility of PTX-TTHA was greater than 5 mg/mL, which was about 7140-fold higher than that of paclitaxel (<0.7 µg/mL). PTX-TTHA (10-105 nmol/L) could significantly inhibit breast cancer proliferation and induce apoptosis by stabilizing microtubules and arresting the cell cycle in the G2/M phase in vitro, with its therapeutic effect and mechanism similar to paclitaxel. However, when the MDA-MB-231 cell-derived xenograft (CDX) tumor model received PTX-TTHA (13.73 mg/kg) treatment once every 3 days for 21 days, the tumor inhibition rate was up to 77.32%. Furthermore, PTX-TTHA could inhibit tumor proliferation by downregulating Ki-67, and induce apoptosis by increasing pro-apoptotic proteins (Bax, cleaved caspase-3) and TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and reducing anti-apoptotic protein (Bcl-2). Moreover, PTX-TTHA demonstrated no sign of acute toxicity on vital organs, hematological, and biochemical parameters at the limit dose (138.6 mg/kg, i.v.). Our study indicated that PTX-TTHA showed better water solubility than paclitaxel, as well as comparable in vitro and in vivo antitumor activity in TNBC models. In addition, the antitumor mechanism of PTX-TTHA was related to microtubule regulation and apoptosis signaling pathway activation.

Methoxypolyethylene Glycol-Substituted Zinc Phthalocyanines for Multiple Tumor-Selective Fluorescence Imaging and Photodynamic Therapy.

Highly tumor-tissue-selective drugs are a prerequisite for accurate diagnosis and efficient photodynamic therapy (PDT) of tumors, but the currently used fluorescent dyes and photosensitizers generally lack the ability for high accumulation and precise localization in tumor tissues. Here we report that monomethoxy polyethylene glycol (MPEG)-modified zinc phthalocyanine (ZnPc) can be selectively accumulated in multiple tumor tissues, and that the selectivity is controlled by the chain length of MPEG. MPEG-monosubstituted ZnPcs with different chain lengths were synthesized, among which the shorter chain (mw < 2k)-modified ZnPc did not show tumor tissue selectivity, while MPEG2k-5k-substituted ZnPc could be rapidly and selectively accumulated in H22 tumor tissues in mice after intravenous injection. Especially, MPEG4k-Pc showed the best tumor tissue selectivity with a tumor/liver (T/L) ratio of 1.7-2.2 in HepG2, MDA-MB231, AGS, and HT-29 tumor-bearing mice. It also exhibited potent photodynamic therapy effects after one PDT treatment, and tumor growth was significantly inhibited in H22-bearing mice with an inhibition rate over 98% and no obvious toxicity. Consequently, MPEG-modified ZnPc could serve as a potential platform for selective fluorescence imaging and photodynamic therapy of multiple tumors.

Bidirectional grating based interleaved angled MMI for high-uniformity wavelength division (de)multiplexing and surface-normal fiber packaging.

We propose and experimentally demonstrate a vertical fiber interfacing interleaved angled multimode interference (MMI) coupler for wavelength-division multiplexing (WDM) applications. This four-channel WDM device comprises two 1×2 angled MMI couplers and a bidirectional grating-based Mach-Zehnder interferometer (MZI) structure. In the MZI optical interleaver, the uniform bidirectional grating functions as both the perfectly vertical grating coupler and the 3 dB power splitter. Benefitting from the flat-top coupling spectrum of the grating coupler, a high-uniformity wavelength-division (de)multiplexing can be achieved with a simulated insertion loss of 3.15-3.36 dB (the nonuniformity of 0.22 dB). The angled MMIs (AMMIs) are designed and optimized using the eigenmode expansion method. For wavelength matching between the MZI and AMMIs, the circuit simulation model of the interleaved AMMI is built by importing the S-parameter matrices of all the optical components extracted from the physical level simulations. The device was fabricated using standard CMOS technology and all the features were patterned with the 193-nm deep-UV lithography. Experimental results obtained without thermal tuning are in good agreement with the simulation results. The device exhibits an insertion loss of 4.5-4.65 dB (nonuniformity of 0.15 dB), channel spacing of 10 nm, and cross talk of -(21.62-26)dB.

Use of the Move to Emptiness Technique, A Mind-Body Exercise for Treating Trauma and Post-Traumatic Stress Disorder: A Case Report.

CONTEXT: The paper reports a case of trauma treated by the Move to Emptiness Technique (MET), which is a therapy to alleviate patient's physical or psychological symptom related to trauma by combining Qigong with imagery, metaphor and suggestions. OBJECTIVE: To introduce MET and report treating a patient with trauma using MET. INTERVENTION: The patient was guided to visualize a symbolic object that represented the physical or psychological symptom of the traumatic experience, and visualize moving the symbolic object to the farthest possible space of "emptiness", where the object became imperceptible. At the same time, the patient embodied the physical and emotional sensations of the symbolic object and its container, and focused on the changes in his sensations when moving them. OUTCOME MEASURES: A self-assessment was used to score the patient's distress form 0 to 10, 10 being the worst before and after intervention. RESULTS: The score of distress dropped form 8/10 to 2/10. The patient improved a lot and was better able to manage his emotions and communicate with his parents after resolving his conflict. CONCLUSIONS: MET may be an alternative to commonly used trauma-focused treatments. It is safe and easy to learn for therapists and patients.

Novel Homo-Bivalent and Polyvalent Compounds Based on Ligustrazine and Heterocyclic Ring as Anticancer Agents.

Bivalent and polyvalent inhibitors can be used as antitumor agents. In this experiment, eight ligustrazine dimers and seven ligustrazine tetramers linked by alkane diamine with different lengths of carbon chain lengths were synthesized. After screening their antiproliferation activities against five cancer cell lines, most ligustrazine derivatives showed better cytotoxicity than the ligustrazine monomer. In particular, ligustrazine dimer 8e linked with decane-1,10-diamine exhibited the highest cytotoxicity in FaDu cells with an IC50 (50% inhibiting concentration) value of 1.36 nM. Further mechanism studies suggested that 8e could induce apoptosis of FaDu cells through the depolarization of mitochondrial membrane potential and S-phase cell cycle arrest. Inspired by these results, twenty-seven additional small molecule heterocyclic dimers linked with decane-1,10-diamine and nine cinnamic acid dimers bearing ether chain were synthesized and screened. Most monocyclic and bicyclic aromatic systems showed highly selective anti-proliferation activity to FaDu cells and low toxicity to normal MCF 10A cells. The structure-activity relationship revealed that the two terminal amide bonds and the alkyl linker with a chain length of 8-12 carbon were two important factors to maintain its antitumor activity. In addition, the ADMET calculation predicted that most of the potent compounds had good oral bioavailability.

Photothermally triggered disassembly of a visible dual fluorescent poly(ethylene glycol)/α-cyclodextrin hydrogel.

The real-time tracking and adjustment of the disassembly and status of hydrogels in vivo are important challenges to accurate and precise assessment. In this article, a photothermally controllable, visible, dual fluorescent thermosensitive hydrogel was designed and developed based on a porphyrin-poly(ethylene glycol)/IR-820-α-cyclodextrin hydrogel. Due to the photothermal effect and fluorescence emission of IR-820, it can exert the dual functions of photothermal control and fluorescence imaging tracking. The IR-820 conjugated hydrogel can regulate the hydrogel disassembly by the photothermal effect of IR-820. Furthermore, each component of the hydrogel can be tracked by the fluorescence of IR-820 and porphyrin. Fluorescence imaging tracking and remote photothermal control were merged into the visible and controlled hydrogel disassembly after subcutaneous injection using mice as models. The dual fluorescence imaging visualization of cyclodextrin/poly(ethylene glycol) hydrogels revealed the disassembly process by tracking each component, and the hydrogel disassembly can be efficiently accelerated under laser irradiation with the photothermal effect of IR-820. This affords an important basis for understanding the disassembly process of the poly(ethylene glycol)/α-cyclodextrin hydrogel.

An Optimal Radial Basis Function Neural Network Enhanced Adaptive Robust Kalman Filter for GNSS/INS Integrated Systems in Complex Urban Areas.

Inertial Navigation System (INS) is often combined with Global Navigation Satellite System (GNSS) to increase the positioning accuracy and continuity. In complex urban environments, GNSS/INS integrated systems suffer not only from dynamical model errors but also GNSS observation gross errors. However, it is hard to distinguish dynamical model errors from observation gross errors because the observation residuals are affected by both of them in a loosely-coupled integrated navigation system. In this research, an optimal Radial Basis Function (RBF) neural network-enhanced adaptive robust Kalman filter (KF) method is proposed to isolate and mitigate the influence of the two types of errors. In the proposed method, firstly a test statistic based on Mahalanobis distance is treated as judging index to achieve fault detection. Then, an optimal RBF neural network strategy is trained on-line by the optimality principle. The network's output will bring benefits in recognizing the above two kinds of filtering fault and the system is able to choose a robust or adaptive Kalman filtering method autonomously. A field vehicle test in urban areas with a low-cost GNSS/INS integrated system indicates that two types of errors simulated in complex urban areas have been detected, distinguished and eliminated with the proposed scheme, success rate reached up to 92%. In particular, we also find that the novel neural network strategy can improve the overall position accuracy during GNSS signal short-term outages.

Vertical Charge Transport via Small Polaron Hopping within TIPS-Pentacene Lamellar Single Crystal.

A modified liquid method is employed to grow an ultralarge 6,13-bis(triisopropylsilylethynyl)pentacene crystal, ensuring fabrication and measurements of the two terminal devices. The hole transport mechanism is studied by analyzing the space charge limited currents (SCLCs) at various temperatures. Modified SCLC theory with a small polaron hopping model is developed and employed to successfully simulate the I-V curves. Values of effective hopping distance, transfer integral, and reorganization energy are extracted and reasonably discussed. A scenario is suggested that hopping transport takes place from one molecule to its nearest neighbor along the c-axis, with every molecule acting as a trapping center.

Anti-inflammatory effect of combined tetramethylpyrazine, resveratrol and curcumin in vivo.

BACKGROUND: Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo. METHODS: The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD50 was measured based on the acute oral toxicity (AOT) standard method. RESULTS: The best formulation was the three components combined at the same mass proportion revealed by the Uniform Design methodology. This combination could significantly reduce the paw swelling in acute paw swelling mouse model, could reduce paw swelling and alleviate the damage in joint structural of ankle, cartilages and fibrous tissue in CIA rat model. The dose relationship was clear in both cases. Immunohistochemical staining of ankle tissue revealed that TRC combination was able to inhibit the expression of NF-κB p65 and TNF-α which were closely related to the inflammatory process. Analysis of serum mediators revealed TRC combination could inhibit the production of TNF-α, IL-1ß, and IL-6 in the serum. Toxic study revealed this formulation was low toxic, LD50 was larger than 5 g/kg, both the level of ALT and AST and histopathology in the liver and kidney exhibited no distinctions between the TRC combination and the blank group, no mortality occurred at the administered doses of 5 g/kg. CONCLUSIONS: The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order of stimuli. Obvious tail-flick movements were observed. The TFL value of transient pain was 3.0 ± 0.8 s, and it was 4.4 ± 1.8 s for tonic pain stimulation. This study shows that our novel design can provide effective stimulation of transient pain and stable tonic pain. Furthermore, it can also provide a reliable combination of transient and consistent stimulations for basic studies of pain perception.

Design, synthesis and anticancer activity of matrine-1H-1,2,3-triazole-chalcone conjugates.

A series of novel matrine-1H-1,2,3-triazole-chalcone conjugates was synthesized and their anticancer activity against A549, Bel-7402, Hela, and MCF-7 cancer cells was evaluated. Most of the conjugates displayed higher potency than their components. Compounds 6h and 6i exhibited more potent anticancer activity than 5-fluorouracil against the four tested human cancer cell lines and lower cytotoxicity to NIH3T3 normal cells. Flow cytometry tests demonstrated that compound 6h could induce apoptosis of A549 cells in a concentration-dependent manner. Moreover, 6h could efficiently suppress human tumor growth in mouse xenograft model without causing obvious toxicities.

Susceptibility of methicillin-resistant Staphylococcus aureus to photodynamic antimicrobial chemotherapy with α-D-galactopyranosyl zinc phthalocyanines: in vitro study.

The incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) is increasing globally, making urgent the discovery of novel alternative therapies for infections. Photodynamic antimicrobial chemotherapy (PACT), based on oxidative damage to subcellular structures, has the advantage of circumventing multidrug resistance, and is becoming a potential therapeutic modality for methicillin-resistant bacteria. The key to PACT is photosensitization. This study demonstrates the efficiency of PACT using α-D-galactopyranosyl zinc phthalocyanines (T1-T4) for the photosensitization of MRSA, Escherichia coli, and Pseudomonas aeruginosa. Bacterial suspensions were illuminated with 650-nm light from a semiconductor laser at 0.2 W/cm(2), and the energy density was maintained at 6 J/cm(2) in the presence of different concentrations of photosensitizer. The treatment response was evaluated based on the numbers of bacterial colony-forming units. PACT with these phthalocyanines strongly affected MRSA, but weakly affected E. coli and P. aeruginosa. The efficiency of PACT on MRSA with these four phthalocyanine compounds decreased in the order T1 > T2 > T3 > T4. T1-PACT eliminated >99% of MRSA in a concentration range of 25-50 µM and at an energy density of 6 J/cm(2). Uptake measurements revealed that the PACT effect correlated with the bacterial uptake of the photosensitizer and that 4-30-fold more T1 than T2-T4 was taken up by the MRSA strain, which was confirmed with laser confocal microscopy. These data suggest that T1 is an efficient PACT photosensitizer for MRSA.

Saccharide substituted zinc phthalocyanines: optical properties, interaction with bovine serum albumin and near infrared fluorescence imaging for sentinel lymph nodes.

Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1-(ß-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and [2,9(10), 16(17),23(24)-tetrakis((1-(ß-D-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared fluorescence agents. Their interaction with bovine serum albumin was investigated by fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. Near infrared imaging for sentinel lymph nodes in vivo was performed using nude mice as models. Results show that saccharide- substituted zinc phthalocyanines have favourable water solubility, good optical stability and high emission ability in the near infrared region. The interaction of lactose-substituted phthalocyanine with bovine serum albumin displays obvious differences to that of glucose- substituted phthalocyanine. Moreover, lactose-substituted phthalocyanine possesses obvious imaging effects for sentinel lymph nodes in vivo.

Photodynamic Therapy of LD4-Photosensitizer Attenuates the Acute Pneumonia Induced by Klebsiella pneumoniae.

Klebsiella pneumoniae is a Gram-negative bacterium that induces acute lung injury (ALI) and inflammation in humans, necessitating immediate hospitalization and treatment. At present, the clinical treatment is largely dependent on hormones or antibiotics but is associated with drawbacks posed by the lack of eradication of the bacterium upon treatment and drug resistance. Therefore, there is an urgent need for novel and effective treatments. The current study investigated the treatment of K. pneumonia-induced ALI using a photosensitizer LD4 in conjunction with photodynamic therapy (PDT). The water content in the lungs (corresponding to edema) of a rat model of pneumonia induced by K. pneumoniae was reduced upon treatment with LD4-PDT. The counts of leukocyte, lymphocyte, and polymorphonuclear leukocyte in the blood were determined in the rat model of pneumonia, as were the concentrations of inflammatory cytokines (estimated using an enzyme-linked immunosorbent assay). The LD4-PDT treatment prominently reduced the levels of interleukin (IL)-6, IL-10, tumor necrosis factor-α, superoxide dismutase, and immune cells. Results suggest that LD4-PDT considerably alleviates the inflammation and oxidative stress caused by K. pneumoniae in the rat model of pneumonia. Furthermore, it could effectively improve the survival rate in the rat model of K. pneumonia-induced pneumonia and ameliorate histological changes while protecting the integrity of the pulmonary epithelial cells. These results highlight the potential application of LD4 as a photosensitizer for treating acute pneumonia induced by K. pneumoniae.

Glycosyl-modified diporphyrins for in vitro and in vivo fluorescence imaging.

The application of probes for optical imaging is becoming popular as they have high safety and good biocompatibility. We prepared two kinds of glycosyl-modified diporphyrins, and their potentials as fluorescent probes were tested for the first time. After preparation of the glycosyl-modified porphyrin monomers, Ag-promoted coupling of the monomers was used to obtain glucose-modified porphyrin dimer (GPD) and lactose-modified porphyrin dimer (LPD). The strong interaction between the two porphyrin rings achieves red-shifted emission, and thus circumvents autofluorescence and light-scattering in biological samples. Although the glycosylation improves solubility, it also yielded selective attachment to cell membranes, and to chorions of early developmental-stage zebrafish. Patch-clamp experiments revealed the biocompatibility and low toxicity of GPD and LPD. Moreover, an in vivo imaging experiment provided direct evidence that zebrafish chorion contains sugar-binding proteins. The modification and derivatization make porphyrins potential bioimaging probes for specific optical imaging.

Lactose substituted zinc phthalocyanine: a near infrared fluorescence imaging probe for liver cancer targeting.

A near infrared fluorescence probe, lactose substituted zinc phthalocyanine, [2,9(10),16(17),23(24)-tetrakis((1-(ß-d-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxyl)phthalocyaninato] zinc(II), was synthesized via click reaction. Structural characterization and optical experiment demonstrated its excellent biocompatibility and fluorescence imaging ability. Near infrared fluorescence imaging in vivo for liver cancer, lung cancer and melanoma cancer with tumor bearing nude mice as models demonstrated that lactose substituted zinc phthalocyanine has specifically targeting ability to liver cancer while no targeting to lung cancer or melanoma, which implied its potential in liver cancer diagnosis as a near infrared optical probe.