Molecular engineering design of twisted-backbone pure Type-I organic photosensitizers for hypoxic photodynamic therapy.

Photodynamic therapy (PDT), an emerging tumor therapeutic strategy has received tremendous attention. Enslaved by the high dependence of oxygen, Type-II photosensitizers (PSs) mediated PDT is restricted by the hypoxic environment of tumors. By transferring electrons to water or other substrates instead of oxygen, Type-I PSs hold the promise of achieving an ideal therapeutic effect under hypoxic conditions. In this study, three twisted-backbone PSs (CBz-TQs-1, CBz-TQs-2 and CBz-TQs-3) are synthesized and studied. Owing to different substituent effects, the ROS generation mechanism transfers from pure Type-II of their prototype PSs (TQs-1, TQs-2 and TQs-3) to mixed Type-I/II of CBz-TQs-1 and CBz-TQs-2 to pure Type-I of CBz-TQs-3. Moreover, CBz-TQs-3 exhibits an ultra-high ROS quantum yield (∼1.0). The in vitro and in vivo PDT effects of water-dissolvable nanoparticles (NPs) of CBz-TQs-3 are investigated. The results show that the phototoxicity of CBz-TQs-3 is not affected by hypoxic environments. In addition, a remarkable tumor ablation can be found after CBz-TQs-3 NPs mediated PDT on Balb/c mice with xenograft tumors. It proves that a twisted backbone strategy is beneficial for designing pure Type-I PSs with high-efficient hypoxic PDT.

Porphyrin Derivative with Binary Properties of Photodynamic Therapy and Water-Dependent Reversible Photoacidity Therapy for Treating Hypoxic Tumor.

Porphyrin photosensitizers are the classic drugs in clinical photodynamic therapy (PDT), but the hypoxia of tumor environment and the rapid oxygen consumption of PDT severely weaken their therapeutic effect. A recently reported water-dependent reversible photoacidity therapy (W-RPAT) is O2-independence, providing a solution for the treatment of hypoxic tumors. In this work, TPP-O-PEG5, a porphyrin derivative with binary properties of PDT and W-RPAT, is designed and synthesized for the first time. The nanoparticles (NPs) of TPP-O-PEG5 encapsulated with DSPE-mPEG2000, an amphiphilic polymer approved by Food and Drug Administration, can simultaneously produce reactive oxygen species and H+ under irradiation of a 660 nm laser, and revert the H+ back under darkness, presenting strong phototoxicity to multiple tumor cell lines with no obvious difference between the IC50 values tested under normoxic (≈20% O2) and hypoxic (<0.5% O2) conditions. Excitingly, in vivo experiments show that the therapeutic effect of TPP-O-PEG5 NPs on large hypoxic tumors is better than that of NPe6, a clinical porphin PDT drug. This work provides a novel strategy for porphyrin photosensitizers to break through the limitation of hypoxic environment, and significantly improve the phototherapeutic effect on hypoxic tumors.

Photoacid Generators for Biomedical Applications.

Photoacid generators (PAGs) are compounds capable of producing hydrogen protons (H+ ) upon irradiation, including irreversible and reversible PAGs, which have been widely studied in photoinduced polymerization and degradation for a long time. In recent years, the applications of PAGs in the biomedical field have attracted more attention due to their promising clinical value. So, an increasing number of novel PAGs have been reported. In this review, the recent progresses of PAGs for biomedical applications is systematically summarized, including tumor treatment, antibacterial treatment, regulation of protein folding and unfolding, control of drug release and so on. Furthermore, a concept of water-dependent reversible photoacid (W-RPA) and its antitumor effect are highlighted. Eventually, the challenges of PAGs for clinical applications are discussed.

A design strategy of pure Type-I thiadiazolo[3,4-g]quinoxaline-based photosensitizers for photodynamic therapy.

Most photosensitizers (PSs) for photodynamic therapy (PDT) can generate singlet oxygen through transferring energy with oxygen, called Type-II PSs. However, the microenvironment of solid tumor is usually anoxic. Type-I PSs can generate reactive oxygen species (ROS) through transferring electron to substrate, showing more efficient in PDT. But pure Type-I PSs are very rare. The relationship between PSs' chemical structure and Type-I mechanism has not been explicitly stated. In this study, two thiadiazolo [3,4-g]quinoxaline (TQ) PSs (PsCBz-1 and PsCBz-2) are synthesized through introducing carbazole groups to the 4,9-position of TQ backbone. Comparing with their prototype PS, 4,9-dibrominated TQ (TQs-4), the introduction of carbazole groups reverses the reaction mechanism of PSs from pure Type-II to pure Type-I. Excitingly, the water-dispersible nanoparticles (NPs) of PsCBz-1 can achieve strong phototoxicity in vitro under both normoxia and hypoxia through Type-I mechanism. In addition, PsCBz-1 NPs also exhibits remarkable PDT antitumor effect in vivo. This study provides a feasible design strategy for pure Type-I PSs.

Photodynamic Therapy-Induced Anti-Tumor Immunity: Influence Factors and Synergistic Enhancement Strategies.

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity towards tumor cells by activating photosensitizers (PSs) with light exposure to produce reactive oxygen species (ROS). Compared to traditional treatment strategies such as surgery, chemotherapy, and radiation therapy, PDT not only kills the primary tumors, but also effectively suppresses metastatic tumors by activating the immune response. However, the anti-tumor immune effects induced by PDT are influenced by several factors, including the localization of PSs in cells, PSs concentration, fluence rate of light, oxygen concentration, and the integrity of immune function. In this review, we systematically summarize the influence factors of anti-tumor immune effects mediated by PDT. Furthermore, an update on the combination of PDT and other immunotherapy strategies are provided. Finally, the future directions and challenges of anti-tumor immunity induced by PDT are discussed.

The upregulation of immune checkpoints after photodynamic therapy reducing immune effect for treating breast cancer.

The immune effect induced by photodynamic therapy (PDT) has a limited effect on breast tumor. This study hypothesized that suppressive immune checkpoints on T cells might upregulate after PDT, which may reduce the antitumor effect of PDT for treating breast tumor. This study explored the alteration of immune checkpoint for the first time. A bilateral subcutaneous transplanted breast tumor mice model was established, and right tumors imitated primary tumors, and left tumors imitated distant tumors. Primary tumors were treated with PDT mediated by hematoporphyrin derivatives (HpD-PDT). Costimulatory molecules (ICOS, OX40, and 4-1BB) and immune checkpoints (PD1, LAG-3, CTLA-4, TIM-3, TIGIT) on tumor infiltrating T cells after HpD-PDT were analyzed by flow cytometry. Antitumor and immune effects were also assessed after HpD-PDT combined with anti-PD1 and LAG-3 antibodies. Primary tumors were suppressed, but distant tumors could not be inhibited after HpD-PDT. The number of T cells was increased, but function did not enhance after HpD-PDT. Additionally, costimulatory molecules (ICOS, OX40, and 4-1BB) were not elevated, but the suppressive immune checkpoints on tumor infiltrating T cells were upregulated after HpD-PDT. Notably, PD1+ LAG-3+ CD4+ T and PD1+ LAG-3+ CD8+ T cells were significantly increased. When PD1 and LAG-3 blockade combined with HpD-PDT, both primary and distant tumors were significantly suppressed, and antitumor immune effects were significantly enhanced. HpD-PDT could upregulate the PD1+ LAG-3+ CD4+ T and PD1+ LAG-3+ CD8+ T cells. Dual blockade of PD1 and LAG-3 immune checkpoints can enhance the antitumor effect of HpD-PDT.

In situ detection of human glioma based on tissue optical properties using diffuse reflectance spectroscopy.

Safely maximizing brain cancer removal without injuring adjacent healthy tissue is crucial for optimal treatment outcomes. However, it is challenging to distinguish cancer from noncancer intraoperatively. This study aimed to explore the feasibility of diffuse reflectance spectroscopy (DRS) as a label-free and real-time detection technology for discrimination between brain cancer and noncancer tissues. Fifty-five fresh cancer and noncancer specimens from 19 brain surgeries were measured with DRS, and the results were compared with co-registered clinical standard histopathology. Tissue optical properties were quantitatively obtained from the diffuse reflectance spectra and compared among different types of brain tissues. A machine learning-based classifier was trained to differentiate cancerous versus noncancerous tissues. Our method could achieve a sensitivity of 93% and specificity of 95% for discriminating high-grade glioma from normal white matter. Our results showed that DRS has the potential to be used for label-free, real-time in vivo cancer detection during brain surgery.

Preventing Post-Traumatic Stress Disorder (PTSD) in rats with pulsed 810 nm laser transcranial phototherapy.

Post-traumatic stress disorder (PTSD) is a debilitating condition that occurs following exposure to traumatic events. Current treatments, such as psychological debriefing and pharmacotherapy, often have limited efficacy and may result in unwanted side effects, making early intervention is a more desirable strategy. In this study, we investigated the efficacy of a single dose of pulsed (10 Hz) 810 nm laser-phototherapy (P-PT) as an early intervention for preventing PTSD-like comorbidities in rats induced by single inescapable electric foot shock following the single prolonged stress (SPS&S). As indicated by the results of the open filed test, elevated plus maze test, and contextual fear conditioning test, P-PT prevented the development of anxiety and freezing behaviors in rats exposed to the SPS&S. We also compared the effects of P-PT and continuous wave 810 nm laser-phototherapy (CW-PT) in preventing PTSD-like comorbidities in rats. The results revealed that P-PT was effective in preventing both freezing and anxiety behavior in stressed rats. In contrast, CW-PT only had a preventive effect on freezing behavior but not anxiety. Additionally, P-PT significantly reduced the c-fos expression in cingulate cortex area 1(Cg1) and infralimbic cortex (IL) of stressed rats, while CW-PT had no significant effects on c-fos expression. Taken together, our results demonstrate that P-PT is a highly effective strategy for preventing the occurrence of PTSD-like comorbidities in rats.

Ultrasonic irradiation enhanced the efficacy of antimicrobial photodynamic therapy against methicillin-resistant Staphylococcus aureus biofilm.

Antimicrobial photodynamic therapy (aPDT) is a non-pharmacological antimicrobial regimen based on light, photosensitizer and oxygen. It has become a potential method to inactivate multidrug-resistant bacteria. However, limited by the delivery of photosensitizer (PS) in biofilm, eradicating biofilm-associated infections by aPDT remains challenging. This study aimed to explore the feasibility of combining ultrasonic irradiation with aPDT to enhance the efficacy of aPDT against methicillin-resistant staphylococcus aureus (MRSA) biofilm. A cationic benzylidene cyclopentanone photosensitizer with much higher selectivity to bacterial cells than mammalian cells were applied at the concentration of 10 µM. 532 nm laser (40 mW/cm2, 10 min) and 1 MHz ultrasound (500 mW/cm2, 10 min, simultaneously with aPDT) were employed against MRSA biofilms in vitro. In addition to combined with ultrasonic irradiation and aPDT, MRSA biofilms were treated with laser irradiation only, photosensitizer only, ultrasonic irradiation only, ultrasonic irradiation and photosensitizer, and aPDT respectively. The antibacterial efficacy was determined by XTT assay, and the penetration depth of PS in biofilm was observed using a photoluminescence spectrometer and a confocal laser scanning microscopy (CLSM). In addition, the viability of human dermal fibroblasts (WS-1 cells) after the same treatments mentioned above and the uptake of P3 by WS-1 cells after ultrasonic irradiation were detected by CCK-8 and CLSM in vitro. Results showed that the percent decrease in metabolic activity resulting from the US + aPDT group (75.76%) was higher than the sum of the aPDT group (44.14%) and the US group (9.88%), suggesting synergistic effects. Meanwhile, the diffusion of PS in the biofilm of MRSA was significantly increased by 1 MHz ultrasonic irradiation. Ultrasonic irradiation neither induced the PS uptake by WS-1 cells nor reduced the viability of WS-1 cells. These results suggested that 1 MHz ultrasonic irradiation significantly enhanced the efficacy of aPDT against MRSA biofilm by increasing the penetration depth of PS. In addition, the antibacterial efficacy of aPDT can be enhanced by ultrasonic irradiation, the US + aPDT treatment demonstrated encouraging in vivo antibacterial efficacy (1.73 log10 CFU/mL reduction). In conclusion, the combination of aPDT and 1 MHz ultrasound is a potential and promising strategy to eradicate biofilm-associated infections of MRSA.

Correlation between soil environment and yield and quality of Sharen (Amomi Fructus) under different planting patterns / 数字中医药（英文）

@#【Objective】  To study the effects of soil environment on the growth, yield, and quality of Sharen (Amomi Fructus) under different planting patterns. 【Methods】  Soil physical and chemical indices and enzyme activities in four periods including early flowering (March), full flowering (June), fruit ripening (September), and late fruit picking (December), were measured under three planting patterns including natural forest, greenhouse, and rubber forest in Xishuangbanna, China. The changes in soil indices during the growth periods of Sharen (Amomi Fructus) under different planting patterns were analyzed, and the differences in plant growth, yield, and quality under different planting patterns were explored. Pearson correlation analysis was used to analyze the relationship between soil indices and Sharen (Amomi Fructus) growth, yield, and quality. Principal component analysis was used to investigate the effects of soil environment under different planting patterns on Sharen (Amomi Fructus) growth, yield, and quality. 【Results】  The soil moisture, available potassium content, and urease activity of the three planting patterns of Sharen (Amomi Fructus) increased initially and decreased afterwards throughout the year; pH and organic matter content showed little change in the whole year. Exchangeable manganese content and acid phosphatase activity gradually increased throughout the year. Hydrolyzed nitrogen content, exchangeable calcium content, available zinc content, protease activity, and sucrase activity decreased initially and increased afterwards throughout the year. Exchangeable magnesium content, available iron content, and catalase activity decreased annually. Total nitrogen content, total phosphorus content, and available phosphorus content fluctuated throughout the year. The total potassium content under natural forest and greenhouse planting decreased throughout the year, while the total potassium content under rubber forest showed an upward trend all year round. The organic matter content, total nitrogen content, total potassium content, available potassium content, available zinc content, urease activity, acid phosphatase activity, and catalase activity under greenhouse were significantly lower than those under natural and rubber forests (P < 0.05). Correlation analysis showed that plant growth, yield, and quality of Sharen (Amomi Fructus) were significantly correlated with soil organic matter, total nitrogen, hydrolyzed nitrogen, total phosphorus, available phosphorus, total potassium, available potassium, exchangeable manganese, exchangeable magnesium, exchangeable calcium, available zinc, urease, acid phosphatase, and invertase (P <  0.05). The results of the principal component analysis indicated that the soil environment of Sharen (Amomi Fructus) under natural forest was the best, followed by rubber forest and greenhouse. The order of its advantages and disadvantages is consistent with the growth index of Sharen (Amomi Fructus), but contrary to the yield of Sharen (Amomi Fructus), indicating that the soil environment directly affects the growth index and nutritional components of plants. 【Conclusion】  Different planting patterns of Sharen (Amomi Fructus) have different soil nutrient content, and the change rules in the growths period are not similar, with some differences. Soil indices have impacts on plant growth, yield, and quality of Sharen (Amomi Fructus). Soil ecological environment is positively correlated with the growth characteristics of Sharen (Amomi Fructus) plants, but has no direct correlation with yield and quality.

Allelopathic Effects of Amomum villosum Lour. Volatiles from Different Organs on Selected Plant Species and Soil Microbiota.

Amomum villosum Lour. is a perennial herb of the Zingiberaceae family, which is widely distributed in Xishuangbanna, Yunnan Province in Southwest China. Large amounts of volatile components contained in this plant enter the surrounding atmosphere and soil through volatilization, foliar leaching, root exudation, and residue decomposition. However, the ecological role of these compounds is currently unclear. The aim of this study was to compare the differences in the composition of volatile oils from stems, leaves, and young fruits of A. villosum, identify chemicals that had allelopathic effects, and explore the effects of the oil on the diversity and composition of soil microbiomes. Volatile oils were obtained by steam distillation and characterized by gas chromatography−mass spectrometry, and then were tested for allelopathic activity using seedlings of Lactuca sativa L. and Lolium perenne L. as test species. The results showed that the oils from stems and leaves were rich in monoterpene hydrocarbons, unlike the oxygenated monoterpenes which dominated oils from young fruits. Leaves > stems > young fruits: this was the order of the allelopathic effects of volatile oils from various A. villosum organs. Among the four main chemical components in the oils, only α-pinene, which is abundant in leaves, had a stronger allelopathic action than the crude oils, implying that it might be a potential allelochemical. Experiments on soil microorganisms indicated that 3.0 mg/mL oil had the greatest effect on the structure of the soil fungal community. It can be concluded that A. villosum is capable of releasing allelochemicals which affect the growth of other plant species and the diversity and community structure of soil microorganisms.

A water-dependent reversible photoacidity strategy for cancer treatment.

In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which contained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) has been found, in which the proton is not dissociated from TQs-Th-PEG5 itself but from a water locked by TQs-Th-PEG5 under the irradiation of a 660 nm laser. After turning off the laser, the produced acid will disappear quickly. This process is repeatable with no consumption of TQs-Th-PEG5. More importantly, water is indispensable. Furthermore, it is confirmed that there is no other element involved in the process except TQs-Th-PEG5, light and water. Excitingly, W-RPA therapy mediated by TQs-Th-PEG5 nanoparticle exhibits remarkable antitumor effect both in vitro and in vivo, especially in hypoxic tumors with diameter larger than 10 mm owing to its oxygen-independent feature. This study not only discovers a W-RPA mechanism but also provides a novel phototherapy strategy for cancer treatment.

Enhanced antimicrobial activity through the combination of antimicrobial photodynamic therapy and low-frequency ultrasonic irradiation.

The rapid increase of antibiotic resistance in pathogenic microorganisms has become one of the most severe threats to human health. Antimicrobial photodynamic therapy (aPDT), a light-based regimen, has offered a compelling nonpharmacological alternative to conventional antibiotics. The activity of aPDT is based on cytotoxic effect of reactive oxygen species (ROS), which are generated through the photosensitized reaction between photon, oxygen and photosensitizer. However, limited by the penetration of light and photosensitizers in human tissues and/or the infiltration of oxygen and photosensitizers in biofilms, the eradication of deeply located or biofilm-associated infections by aPDT remains challenging. Ultrasound irradiation bears a deeper penetration in human tissues than light and, sequentially, can promote drug delivery through cavitation effect. As such, the combination of ultrasound and aPDT represents a potent antimicrobial strategy. In this review, we summarized the recent progresses in the area of the combination therapy using ultrasound and aPDT, and discussed the potential mechanisms underlying enhanced antimicrobial effect by this combination therapy. The future research directions are also highlighted.

In vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® for cancer treatment.

BACKGROUND: Photodynamic therapy (PDT) has been approved for the clinical treatment of cancers. Photosensitizer (PS) is a crucial element of PDT. In the current study, in vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® was performed. METHODS: The physicochemical characteristics of KAE® were compared with chlorin e6. The intracellular distribution of KAE® in HeLa cells was observed by laser scanning confocal microscopy. Reactive oxygen species (ROS) generation was detected through a 2', 7-dichlorodihydrofluorescein diacetate probe. The pharmacokinetics of KAE® was studied in mice. The photodynamic activities of KAE® and porphyrin based PSs were compared both in vitro and in vivo. The biosafety of KAE® in mice was evaluated by pathological section observation, blood routine examination and biochemistry assays. RESULTS: KAE® was readily dissolved in an aqueous solvent in a clinically acceptable concentration and showed a strong absorption at around 660 nm. Most of KAE® was located in the mitochondria of the tumor cells. Compared with hematoporphyrin derivative and 5-aminolevulinic acid, KAE® displayed a higher efficiency in cell killing. Furthermore, it could be completely eliminated from mouse body in 2 days. KAE® had no toxicity to mice under the tested dosage. CONCLUSIONS: Our results suggested that KAE® is an effective and safe PS for PDT in cancer therapy and has a promising prospect for clinical application.

Light intensity alters the effects of light-induced circadian disruption on glucose and lipid metabolism in mice.

Circadian disruption induced by rotating light cycles has been linked to metabolic disorders. However, how the interaction of light intensity and light cycle affects metabolism under different diets remains to be explored. Eighty mice were first randomly stratified into the low-fat diet (LFD, n = 40) or high-fat diet (HFD, n = 40) groups. Each group was further randomly subdivided into four groups (n = 8-12 per group) in terms of different light intensities [lower (LI, 78 lx) or higher intensity (HI, 169 lx)] and light cycles [12-h light:12-h dark cycle or circadian-disrupting (CD) light cycle consisting of repeated 6-h light phase advancement]. Body weight was measured weekly. At the end of the 16-wk experiment, mice were euthanized for serum and pathological analysis. Glucose and insulin tolerance tests were performed during the last 2 wk. The CD cycle increased body weight gain, adipocyte area, glucose intolerance, and insulin resistance of LFD as well as HFD mice under HI but not LI condition. Moreover, the serum and hepatic triglyceride levels increased with LFD-HI treatment, regardless of light cycle. In addition, the CD cycle improved lipid and glucose metabolism under HFD-LI condition. In summary, the detrimental effects of the CD cycle on metabolism were alleviated under LI condition, especially in HFD mice. These results indicate that modulating light intensity is a potential strategy to prevent the negative metabolic consequences associated with jet lag or shift work.NEW & NOTEWORTHY Glucose and lipid homeostasis is altered by the CD cycles in a light-intensity-dependent manner. Lower-intensity light reverses the negative metabolic effects of the CD cycles, especially under HFD feeding. The interaction of light intensity and light cycle on metabolism is independent of energy intake and eating pattern. Glucose metabolic disorders caused by rotating light cycles occur along with compensatory ß-cell mass expansion.

Quantitative assessment of vascular features in port wine stains through optical coherence tomography angiography.

BACKGROUND: Vascular lesions such as port wine stains (PWS) lead to facial and psychological problems, which require careful and precise treatments. The key point of treating PWS is to selectively destroy the abnormal blood vessels. Hence, the in vivo monitoring of targeted vessels is crucial. Optical coherence tomography angiography (OCTA), an emerging label-free imaging tool, facilitates the evaluation of skin structure and vasculature at a high resolution. In this study, we utilised OCTA to capture the structural and vascular morphology in patients with PWS. Moreover, we quantitatively characterised the morphological features of different types of PWS. METHODS: This observational clinical study was conducted on 3 patients with flat PWS and 3 patients with thickened PWS. The age range was 4-27 years, and all of them had not received any treatment before this study. The OCTA images of the PWS lesions and contralateral skin were compared. Vascular morphology was characterized, and ectatic vessel depth was quantified according to the OCTA images. RESULTS: The blood vessels of the PWS lesions tend to had larger diameters and higher densities than those in the contralateral normal skin. The vessel diameters of PWS lesions were 73 ± 14 µm, with high heterogeneity ranging from 10 to >150 µm, however, the vessel diameters of normal skin were 28 ± 2 µm, ranging from 10 µm to 60 µm. In terms of different PWS lesions, the thickened type showed a trend of larger vessel diameter and higher density than those of the purplish red type. The ectatic vessels were located at the depth of 216 ± 13 µm in the PWS skin. CONCLUSIONS: OCTA can facilitate the in vivo three-dimensional visualization of structure and vasculature for PWS lesions. Various quantitative analysis parameters, such as vessel diameter, density, and depth, are typically measured using OCTA. This fact demonstrates the superior capability of OCTA for the precise and comprehensive assessment of PWS lesions.

Ultra-high photoactive thiadiazolo[3,4-g]quinoxaline nanoparticles with active-targeting capability for deep photodynamic therapy.

Improving the effective treatment depth of photodynamic therapy (PDT) is an important issue to resolve for its clinical application. In this study, a new biocompatible photosensitizer (PS), namely TQs-PEG4, based on thiadiazolo[3,4-g]quinoxaline (TQ) with ultra-high photoactive property is designed and synthesized. TQs-PEG4 possesses an ultra-high singlet oxygen quantum yield (ΦΔ = 1.04). After encapsulating it with a biodegradable copolymer (DSPE-mPEG2000-cRGD), well distributed organic TQs-PEG4 nanoparticles (NPs) are formed with good water dispersity and excellent active tumor-targeting property. In vitro PDT experiments reveal that TQs-PEG4 NPs present excellent phototoxicities towards different cancer cell lines with an ultra-low dosage (<0.3 µg mL-1). TQs-PEG4 NP mediated PDT significantly inhibited tumor growth even when the tumor was covered with a 6 mm thick piece of pork tissue under 660 nm laser irradiation. Both the histological analysis and biochemical testing demonstrated the good biosafety of TQs-PEG4 NPs towards mice. This study not only develops an ultra-high photoactive organic PS, TQs-PEG4, but also proves the great potential of TQs-PEG4 NPs for application in deep PDT.

FISH-Based Karyotype Analyses of Four Dracaena Species.

The genus Dracaena is the main source of dragon's blood, which is a plant resin and has been used as traditional medicine since ancient times in different civilizations. However, the chromosome numbers and karyotypes present in this genus remain poorly understood. In this study, fluorescence in situ hybridization (FISH) using oligonucleotide probes for ribosomal DNAs (5S and 45S rDNA) and telomeric repeats (TTTAGGG)3 was applied to analyze 4 related species: Dracaena terniflora Roxb., Dracaena cambodiana Pierre ex Gagnep., Aizong (Dracaena sp.), and Dracaena cochinchinensis (Lour.) S.C. Chen. In all 4 species, both 5S and 45S rDNA showed hybridization signals in the paracentromeric region of a pair of chromosomes; the sizes of the 45S rDNA signals were larger than those of the 5S rDNA. Importantly, the telomeric repeat signals were located in the telomeric regions of almost all chromosomes. The results indicated that the chromosome number of all 4 Dracaena species is 2n = 40, and the lengths of the mitotic metaphase chromosomes range from 0.99 to 2.98 µm. Our results provide useful cytogenetic information, which will be beneficial to future studies in genome structure of the genus Dracaena.

Cyclin G2, a novel target of sulindac to inhibit cell cycle progression in colorectal cancer.

Sulindac has shown significant clinical benefit in preventing colorectal cancer progression, but its mechanism of action has not been fully elucidated. We have found that sulindac sulfide (SS) is able to inhibit cell cycle progression in human colorectal cancer cells, particularly through G1 arrest. To understand the underlying mechanisms of sulindac inhibitory activity, we have demonstrated that Cyclin G2 up-regulation upon SS treatment can substantially delay cell cycle progression by enhancing the transcriptional activity of FOXO3a in human colorectal tumor cells. MiR-182, an oncogenic microRNA known to inhibit FOXO3a gene expression, is also involved in the suppressive effect of SS on cell cycle progression. This process begins with the down-regulation of miR-182, followed by the enhancement of FOXO3a transcriptional activity and the up-regulation of Cyclin G2. To further determine the clinical utility of this axis, we analyzed the expression of miR-182/FOXO3a/Cyclin G2 in human colorectal tumor samples. Our results show not only that there are significant differences in miR-182/FOXO3a/Cyclin G2 between tumors and normal tissues, but also that the synergetic effect of miR-182 and FOXO3a is associated with predicting tumor progression. Our study demonstrates a novel mechanistic axis consisting of miR-182/FOXO3a/Cyclin G2 that mediates sulindac inhibition of cell cycle progression.