Silver Nanoparticle-Loaded Titanium-Based Metal-Organic Framework for Promoting Antibacterial Performance by Synergistic Chemical-Photodynamic Therapy.

The abuse of antibiotics leads to an increasing emergence of drug-resistant bacteria, which not only causes a waste of medical resources but also seriously endangers people's health and life safety. Therefore, it is highly desirable to develop an efficient antibacterial strategy to reduce the reliance on traditional antibiotics. Antibacterial photodynamic therapy (aPDT) is regarded as an intriguing antimicrobial method that is less likely to generate drug resistance, but its efficiency still needs to be further improved. Herein, a robust titanium-based metal-organic framework ACM-1 was adopted to support Ag nanoparticles (NPs) to obtain Ag NPs@ACM-1 for boosting antibacterial efficiency via synergistic chemical-photodynamic therapy. Apart from the intrinsic antibacterial nature, Ag NPs largely boost ROS production and thus improve aPDT efficacy. As a consequence, Ag NPs@ACM-1 shows excellent antibacterial activity under visible light illumination, and its minimum bactericidal concentrations (MBCs) against E. coli, S. aureus, and MRSA are as low as 39.1, 39.1, and 62.5 µg mL-1, respectively. Moreover, to expand the practicability of Ag NPs@ACM-1, two (a dense and a loose) Ag NPs@ACM-1 films were readily fabricated by simply dispersing Ag NPs@ACM-1 into heated aqueous solutions of edible agar and sequentially cooling through heating or freeze-drying, respectively. Notably, these two films are mechanically flexible and exhibit excellent antibacterial activities, and their antimicrobial performances can be well retained in their recyclable and remade films. As agar is nontoxic, degradable, inexpensive, and ecosustainable, the dense and loose Ag NPs@ACM-1 films are potent to serve as recyclable and degradable antibacterial plastics and antibacterial dressings, respectively.

Polysaccharide of Atractylodes macrocephala Koidz(PAMK) protects against DEHP-induced apoptosis in grass carp hepatocytes.

Di(2-ethylhexyl) phthalate (DEHP) is a new environmental pollutant, which is widely used in plastic additives. DEHP and its metabolites pollute surface water and threaten the survival of fish. In order to investigate the mechanism of DEHP-induced apoptosis on grass carp hepatocytes, we treated grass carp hepatocytes with DEHP, and selected Atractylodes macrocephala Koidz (PAMK) to study its inhibitory effect on DEHP. The results showed that after DEHP exposure, apoptosis related proteins expression were increased significantly, leading to hepatocytes apoptosis. Moreover, AO/EB staining and Hoechst staining also showed that the number of apoptotic cells increased after DEHP exposure. It should be noted that PAMK simultaneous treatment could alleviate apoptosis induced by DEHP. The innovation of this study is that the application of Chinese herbal medicine (PAMK) to antagonize the damage of DEHP in fish was investigated for the first time. This study indicated that traditional Chinese medicine can also be used in fish production to reduce the accumulation of food-derived drugs.

Association of sirtuins (SIRT1-7) with lung and intestinal diseases.

"Exterior-interior correlation between the lung and large intestine" is one of the important contents of traditional Chinese medicine. This theory describes the role of the lung and the intestine in association with disease treatment. The "lung-gut" axis is a modern extension of the "exterior-interior correlation between lung and large intestine" theory in TCM. Sirtuin (SIRT) is a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme family with deacetylase properties, which is highly conserved from bacteria to humans. The sirtuin defines seven silencing regulatory proteins (SIRT1-7) in human cells. It can regulate aging, metabolism, and certain diseases. Current studies have shown that sirtuins have dual characteristics, acting as both tumor promoters and tumor inhibitors in cancers. This paper provides a comparative summary of the roles of SIRT1-7 in the intestine and lung (both inflammatory diseases and tumors), and the promoter/suppressor effects of targeting SIRT family microRNAs and modulators of inflammation or tumors. Sirtuins have great potential as drug targets for the treatment of intestinal and respiratory diseases. Meanwhile, it may provide new ideas of future drug target research.

Glycyrrhetinic acid reverses antibiotic-induced intestinal epithelial injury through RNA-binding protein human antigen R (HuR).

BACKGROUND: The application/abuse of antibiotics can cause antibiotic-induced intestinal injury (AIJ), a typical clinical issue that disturbs intestinal homeostasis. However, the underlying post-transcriptional mechanism of AIJ remains unknown. Glycyrrhetinic acid (GA) is one of the main components of Glycyrrhiza uralensis Fisch. and Glycyrrhiza inflata Batalin (Fabaceae), and findings of our previous study showed that GA can maintain intestinal homeostasis post-transcriptionally through the RNA-binding protein human antigen R (HuR). PURPOSE: This study aimed to elucidate the role of HuR in AIJ and the protective effects of GA on AIJ. STUDY DESIGN AND METHODS: Clindamycin hydrochloride was used to clarify the effect of the antibiotic on the intestinal epithelium. Intestinal epithelium cell-6 (IEC-6) and Caco2 cells were used to demonstrate the in vitro effects of the antibiotic and GA on intestinal cells. HuR plasmid and siRNA were used to overexpress or silence HuR in vitro. SD rats were induced by using clindamycin hydrochloride capsules (250 mg/kg i.g.) for 7 consecutive days to construct the in vivo AIJ model. Rats of the AIJ model group were administrated GA (10 and 20 mg/kg i.g.) for 7 days, and subsequently, the protective effect of GA on the intestinal epithelium was evaluated. RESULTS: In vitro results showed that the antibiotic (150-500 µM) suppressed proliferation, induced a delay in restitution after wounding, and caused cell cycle arrest at the G0/G1 phase in IEC-6 and Caco-2 cells. Moreover, the expression levels of HuR and its downstream gene, occludin and cyclin D1, decreased after treatment with the antibiotic (500 µM). Overexpression of HuR and GA (10 and 20 µM) reversed the antibiotic-induced inhibition of proliferation and G0/G1 phase arrest, and the antibiotic-induced decrease in HuR, occludin, and cyclin D1 expression was reversed after GA treatment (10 and 20 µM) in IEC-6 cells. In vivo results revealed the antibiotic-induced epithelial injury of both the small intestines (shortened and spared mucosa) and the large intestines (injured/deformed glands, reduced number of cup cells, and evident inflammatory cell infiltration), all of which were ameliorated after GA treatment (10 and 20 µM). CONCLUSION: Antibiotics induce intestinal epithelial injury through HuR, and GA can exert a protective effect on AIJ by restoring HuR levels.

Spirostane saponins with a rearranged A/B ring system isolated from the rhizomes of Ophiopogon japonicus.

In this study, the popular food and medicinal herb Ophiopogon japonicus was investigated alongside a 70% ethanol extract of its rhizomes, revealing twenty-three steroidal glycosides with four undescribed steroidal saponins, named ophiopogonols A-D. Among them, ophiopogonols A-B are two unusual spirostanols with a rearranged A/B ring system (5/7/6/5/5/6 ring system) that have not previously been identified in plants. The chemical structures of all isolated steroidal glycosides were elucidated by comprehensive analysis through chemical methods, HRESIMS, and NMR spectroscopy. Further, putative biosynthetic pathways for ophiopogonols A-B were proposed. In addition, based on traditional applications of O. japonicus, cytotoxic effects of the isolates were evaluated using human large cell lung carcinoma cells (NCI-H460 cells). Sprengerinin C displayed a remarkable cytotoxic effect with IC50 values of 2.1 ± 0.8 µM by inducing apoptosis and G2/M phase cycle arrest in the NCI-H460 cell line.

Apigenin exerts chemopreventive effects on lung injury induced by SiO2 nanoparticles through the activation of Nrf2.

Apigenin (APG) is a flavonoid widely distributed in fruits, vegetables, and herbs, with comprehensive pharmacological effects. In this paper, we report that APG can elicit a protective effect, which is comparable to those induced by gymnoside II/n-BuOH extracts of Bletilla striata, on SiO2-induced lung injury in vitro and in vivo. In vitro experiments showed that APG (25 µM) could restore the SiO2-decreased A549 cell viability and lower the apoptotic rate and the production of intracellular reactive oxygen species (ROS) in A549 cells treated with nm SiO2. Western blot results showed that APG (25 µM) could increase the level of Nuclear factor E2-related factor 2 (Nrf2) and its downstream proteins. In vivo experiments showed that APG (20 mg/kg) could potently alleviate the SiO2-elicited lung injury by enhancing the Nrf2 expression and thereby suppressing Bax/Bcl-2 pathway. The present study suggests that APG can significantly alleviate the SiO2-induced lung injury both in vitro and in vivo through, at least partially, activating Nrf2 expression.

PAMK Relieves LPS-Induced Enteritis and Improves Intestinal Flora Disorder in Goslings.

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) is a biologically active component of Atractylodes macrocephala, which has the effect of maintaining the immune homeostasis of the body. Therefore, this study constructed a model of PAMK to relieve LPS-induced gosling enteritis and observed the morphological changes of the small intestine after HE staining. ELISA was used to detect serum CRP, IL-1ß, IL-6, and TNF-α levels; immunohistochemistry was used to detect the positive rate of IgA in the small intestine; TLR4, occludin, ZO-1, cytokines, and immunoglobulin mRNA expression in the small intestine were detected by qPCR; and intestinal flora of gosling excrement was analyzed by 16S rDNA sequencing to analyze the protective effect of PAMK on goslings enteritis and the impact on intestinal flora. The results showed that PAMK relieves LPS-induced gosling enteritis by maintaining the small intestine morphology, cytokine, tight junctions, and immunoglobulin relatively stable and improving the disorder of intestinal flora.

n-BuOH extract of Bletilla striata exerts chemopreventive effects on lung against SiO2 nanoparticles through activation of Nrf2 pathway.

BACKGROUND: SiO2 nanoparticles (nm SiO2) are ubiquitous in daily life and are acknowledged to be detrimental to human health. Bletilla striata is a traditional medicine used for generations in China and its polysaccharide has the anti-pulmonary fibrosis effect. PURPOSE: To investigate the lung protective effect of the small molecules (n-BuOH extract) of B. striata and clarify the underlying mechanism. STUDY DESIGN AND METHODS: C57BL/6 mice were subjected to intratracheal instillation with nm SiO2 nanoparticle suspension (7 mg/kg) to construct the in vivo model of nm SiO2-induced lung injury. The chemical profile of the n-BuOH extract of B. striata was investigated by HPLC analysis using authentic samples isolated from B. striata. Gymnoside II with the most potent chemoprotective capacity in the n-BuOH extract was used to clarify the potential bio-active molecular basis of the n-BuOH extract using in vitro experiments. The cytotoxicity, apoptosis, oxidative stress, and the Nrf2 signaling pathway were examined in SiO2-induced A549 cells. ML385 was adopted to down-regulate the Nrf2 expression. RESULTS: The n-BuOH extract of B. striata (40 mg/kg) could alleviate the SiO2-induced lung injury by increasing Nrf2 expression and thereby suppressing Bax/Bcl-2 pathway in the nm SiO2-induced mice model. The chemical profile study showed that militarine, gymnoside II, and 4-allyl-2, 6-dimethoxyphenol glucoside were the main constituents of n-BuOH extract. Studies on gymnoside II revealed that it could partially restore the SiO2-induced decline in cell viability while did not affect the growth of normal A549 cells within the concentration range of 1-50 µM, suggesting a protective effect against nm SiO2 in lung A549 cells. The hoechst 33258 staining, flow cytometry, and western blot experiments demonstrated that gymnoside II (25 µM) could partially reverse the SiO2-induced cell apoptosis and ROS production by enhancing Nrf2, HO-1, and γ-GCSc expressions and Nrf2 silencing by ML385 abrogated the effects of gymnoside II (25 µM) on apoptosis and ROS production in A549 cells. CONCLUSION: The present study suggests that in addition to the polysaccharide, small molecules (n-BuOH extract) of B. striata can also elicit a protective effect on lung injuries through the Nrf2-dependent mechanism and gymnoside II is one of the main bio-active constituents contributing to the n-BuOH extract-elicited lung protective effect against nm SiO2.

CircRNAs in Lung-intestinal Axis Cancer.

The "exterior-interior relationship between the lung and the large intestine" is a basic theory in Traditional Chinese Medicine (TCM), which has been confirmed by mounting evidence, and the lung-intestinal axis can be seen as an extension of this theory. Circular RNAs (circRNAs) are a kind of conserved and structurally stable noncoding RNAs, which have been found to be differentially expressed and associated with the development of cancer in malignant tumors. Many studies have found that circRNAs play an important role in lung and intestinal cancers. This review focuses on circRNAs and reveals that there are common circRNAs that are both highly or poorly expressed in lung-intestinal axis cancers and most of them regulate the proliferation, migration, and invasion of cancer cells by sponging miRNAs. These results not only provide new evidence and research ideas for the "exterior-interior relationship between the lung and the large intestine", but also suggest that circRNAs can be new potential therapeutic targets for the future drug research of lung-intestinal axis diseases.

Licochalcone A reverses NNK-induced ectopic miRNA expression to elicit in vitro and in vivo chemopreventive effects.

BACKGROUND: Chemoprevention is the best cost-effective way regarding cancers. MicroRNAs (miRNAs) have been reported to be differentially expressed during the development of lung cancer. However, if lung cancer prevention can be achieved through modulating miRNAs expression so far remains unknown. PURPOSE: To discover ectopically expressed miRNAs in NNK-induced lung cancer and clarify whether Licochalcone A (lico A) can prevent NNK-induced lung cancer by modulating miRNA expression. STUDY DESIGN AND METHODS: A/J mice were used to construct a lung cancer model by intraperitoneal injection with physiological saline NNK (100 mg/kg). Chemopreventive effects of lico A against lung cancer at 2 mg/kg and 20 mg/kg doses were evaluated in vivo. MicroRNA array and RT-qPCR were used to assess the expression levels of miRNAs. MLE-12 cells were treated with 0.1 mg/ml NNK, stimulating the ectopic expression pattern of miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p. miR-144-3p mimics and inhibitors were used to manipulate miR-144-3p levels. The effects of lico A (10 µM) on cell cycle distribution, apoptosis, and the expression of CK19, RASA1, miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p in NNK-treated MLE-12 cells were studied. RESULTS: The expression levels of miR-144-3p, miR-20a-5p, and miR-29c-3p increased, while those of let-7d-3p and miR-328-3p decreased in both NNK-induced A/J mice and MLE-12 cells. Lico A could reverse the NNK-induced ectopic miRNA (miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p) expression both in vivo and in vitro and elicit in vivo lung cancer chemopreventive effect against NNK. In MLE-12 cells, the overexpression of miR-144-3p elicited the same effect as NNK regarding the expression of lung cancer biomarker CK19; the silencing of miR-144-3p reversed the effect of NNK on cell cycle distribution and apoptosis. Lico A could reverse the effect of NNK on the expression of miR-144-3p, CK19, and RASA1 (predicted target of miR-144-3p). CONCLUSION: The present study suggests that miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p were involved in the in vivo pathogenesis of NNK-induced lung cancer, and lico A could reverse the effect of NNK both in vivo and in vitro to elicit lung cancer chemopreventive effects through, at least partially, these five ectopically expressed miRNAs, especially miR-144-3p.

Selenium-Alleviated Hepatocyte Necrosis and DNA Damage in Cyclophosphamide-Treated Geese by Mitigating Oxidative Stress.

Selenium (Se) has been well recognized as an immune-enhancing agent with antioxidant and anti-tumor properties. The commonly used chemotherapy drug, cyclophosphamide (CTX), induces liver injury by increasing the reactive oxygen species (ROS) level. However, little is known about how Se alleviates CTX-induced liver injury in geese. In this study, 90 male Magang geese (3 days old) were randomly allocated into three groups (control, CTX, and Se + CTX group) with three replicates per group and ten geese per replicate. The control and CTX groups were fed a basal diet (Se content was 0.03 mg/kg). The Se + CTX group was fed a basal diet containing 0.44 mg/kg sodium selenite (Se content was 0.2 + 0.03 mg/kg). The control group was injected with 0.5 mL saline, while the CTX and Se + CTX groups were injected with CTX at 40 mg/kg body weight per day on days 21-23. The liver index, liver histology, and ultra-micromorphology detected antioxidant enzyme activity in the liver and serum. In addition, we detected the liver marker enzymes and protein levels in serum, and hepatocyte DNA damage. Se could alleviate liver development dysregulation, hepatocyte structural damage, the disturbances in antioxidant enzyme (GPx, CAT, and SOD) activity, and malondialdehyde (MDA) levels in the serum and liver. Besides, Se could alleviate the dysregulation of liver marker enzyme (ALT and AST) activity and protein (ALB and TP) levels in the serum, and DNA migration induced by CTX. In conclusion, Se may inhibit hepatocyte necrosis and DNA damage by inhibiting CTX-induced oxidative stress.

Polysaccharide of Atractylodes macrocephala Koidz Enhances Cytokine Secretion by Stimulating the TLR4-MyD88-NF-κB Signaling Pathway in the Mouse Spleen.

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has been reported to have beneficial effects on regulation of immune responses in mammals and poultry. Nonetheless, the immunoregulatory mechanism of action of PAMK remains unclear. The Toll-like receptor 4 (TLR4) signaling cascade has been proved as a classic polysaccharide-regulated pathway. The aim of this study was to explore the effects of PAMK on the TLR4 signaling pathway in the regulation of spleen function in mice. Ninety-six 5-week-old BALB/c female mice were randomly allocated into four groups with three replicates per group and eight mice per replicate in a single-factor completely randomized experimental design. The control group was fed a basic diet (PAMK free); the other three groups were fed 100, 200, or 400 mg/kg PAMK for 28 days. The spleen index, concentrations of cytokines, and mRNA and protein expression levels of genes related to TLR4 signaling were determined in spleen tissue. Compared with the control group, the spleen index significantly increased in all treatment groups. Concentrations of interleukin 2 (IL-2), IL-4, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) in the medium-PAMK group also increased significantly. PAMK in the medium-PAMK group significantly increased both mRNA and protein expression of TLR4, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 (TRAF6), TRAF3, and nuclear factor kappa B (NF-κB) in the spleen. In conclusion, PAMK may increase immune-response capacity of the spleen in mice via TLR4-MyD88-NF-κB signaling.

Isolation and identification of two new compounds from the twigs and leaves of Cephalotaxus fortunei.

Two new compounds, namely 5-hydroxy-7-methoxy-6-methylchromone (1), and sesquiterpene X (6), together with 21 known compounds were isolated from the twigs and leaves of Cephalotaxus fortunei Hook. f. The structures of 1-23 were elucidated on the basis of spectroscopic analysis (1D/2D NMR, HR-ESI-MS and IR) and comparison with literature. The absolute configuration of compound 6 was determined by means of electronic circular dichroism calculation. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing lipopolysaccharide-induced nitric oxide production. Compounds 1 and 6 exhibited weak effects with percentage inhibitions of 24% and 35.60%, respectively. In addition, compounds 4, 9, and 14 have the potential to be developed as therapeutic agents for inflammatory diseases because of their significant anti-inflammatory activities and high content in C. fortunei.

Formation pattern in five types of pollen tetrad in Pseuduvaria trimera (Annonaceae).

In basal angiosperms, there are several types of permanent tetrad but their formation pattern remains elusive. Pseuduvaria trimera has five types of tetrads and is the species with the most abundant tetrad types in Annonaceae. In order to interpret the formation pattern of different tetrad types, pollen development was investigated from the microspore mother cell stage to the bicellular pollen stage and the ultrastructure of pollen wall in the five tetrad types using light microscopy, transmission electron microscopy, and confocal laser scanning microscopy. Both successive and intermediate cytokinesis were observed within the same anther. The nucleus location of the microspores together with cytokinesis determine the number and the spatial arrangement of callose plates, and further have an effect on the tetrad types. The anthers with or without septation and the arrangement of microsporocytes might be also related to the tetrad type. The individual pollen grains within the tetrads are connected with each other by crosswall cohesion and cytoplasmic channels at localized points in the proximal walls. The various types of tetrads, cytokinesis, and cohesion in P. trimera reflect the high diversity in pollen development, which enhances the dramatic variety in pollen morphology in this family. Our observations of the development of tetrads provided some new insights for interpreting the factors influencing the types of tetrads, and reported the existence of a cytoplasmic channel in Annonaceae for the first time.

Effect of Selenium on Ion Profiles and Antioxidant Defense in Mice Livers.

Se entering the mammalian body from diverse sources shows different liver accumulation patterns. However, the effects of Se from diverse sources on the body's I on spectrum and the relationship between the changes in the ion spectrum and antioxidant function are not clear. In this study, 80 3-week-old female mice were randomly divided into four groups: a control group, sodium selenite group, yeast Se group, and seaweed Se group. The estimated Se contents were 0.03, 0.23, 0.23, and 0.23 mg/kg, respectively. The liver was collected from mice on day 60. The results showed that, compared with the control group, sodium selenite significantly reduced Na and Li contents and significantly increased Cr, Ni, Se, and Sb contents (P < 0.05); yeast Se significantly increased Mg, Ca, Si, Cr, Fe, Co, Cu, Se, Sb, and Al contents, and significantly reduced Tl, As, and Hg contents (P < 0.05); seaweed Se significantly increased B, Si, Cr, Fe, Se, As, and Hg contents, and significantly reduced Zn and Tl contents (P < 0.05). The results of antioxidant parameter analysis showed that Se from three sources increased total superoxide dismutase content and significantly reduced malondialdehyde content (P < 0.05), whereas no clear effect was observed on total antioxidant capacity (P > 0.05). Combined with the ion spectrum and antioxidant test results, yeast Se was found to most effectively promote the accumulation of beneficial elements, enhance antioxidant capacity, and reduce the concentration of toxic elements. The variety of ion spectrum antioxidants followed a similar trend, which indicated that the ion spectrum might be related to antioxidant activity.

Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese.

Effect of Dietary Selenium Deficiency on the Cell Apoptosis and the Level of Thyroid Hormones in Chicken.

This study assessed the effect of dietary selenium (Se) deficiency on male reproductive function in chicken. A total of 180 Hy-line laying cocks (1 day old; Weiwei) were randomly divided into 2 groups (n = 90) of Se-deficient chickens and control chickens. The control group was fed a basic diet (containing 0.15 mg of Se/kg). The Se-deficient group was fed a Se-deficient corn-soy basal diet (containing 0.033 mg of Se/kg). Fifteen chickens were killed in each group on days 30, 60, and 90, respectively. Then, serum and testes were collected and used in the detection of experimental index. Results indicated that GSH-Px activity and Bcl-2 mRNA level in the testes and thyroidal triiodothyronine (T3) and free triiodothyronine (FT3) levels in serum by dietary Se deficiency were significantly decreased compared to the corresponding control groups. Se deficiency-treated group showed a significant increase in MDA concent, TUNEL-positive cells, and mRNA level of Bax, Caspase3, and p53 in the testes and thyroidal thyroxine (T4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels in serum. Histopathologically, Se deficiency caused impairments in the testes. These results suggested that dietary Se deficiency exerts significant harmful effects on male reproductive organ and that the intrinsic and extrinsic pathways and the upstream regulators such as p53, Bax, and Bcl-2 were all involved in Se deficiency-induced testicular apoptosis.

Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvß3 in melanoma cancer cells.

BACKGROUND: Thermotherapy has been known to be one of the most effective adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely implemented clinically due to some limitations, such as, inadequate temperature concentrations to the tumor tissue, nonspecific and non-uniform distribution of heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (αvß3) and investigate whether the photo-thermal effect of RGD-GNRs by near infrared radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells. RESULTS: RGD-GNRs could be seen both on the surface of the cell membranes and cytoplasm of A375 cells with high expression of αvß3. After exposed to 808 nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs increased apoptosis (p < 0.001) and decreased the proportion of cells in the more radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the radiosensitivity was also significantly enhanced (DMFSF2: 1.41). CONCLUSION: Results of the current study showed the feasibility of using RGD-GNRs for synergetic RT with photo-thermal therapy. And it would greatly benefit the therapeutic effects of refractory or recurrent malignant cancers.

Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy.

Fluorofenidone (FD) is a novel pyridone agent with significant antifibrotic effects in vitro. The purpose of this study is to investigate the effects of FD on renal interstitial fibrosis in rats with obstructive nephropathy caused by unilateral ureteral obstruction (UUO). With pirfenidone (PD, 500 mg/kg/day) and enalapril (10 mg/kg/day) as the positive treatment controls, the rats in different experimental groups were administered with FD (500 mg/kg/day) from day 4 to day 14 after UUO. The tubulointerstitial injury, interstitial collagen deposition, and expression of type I and type III collagen, transforming growth factor-ß(1) (TGF-ß(1)), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), α-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed. FD treatment significantly attenuated the prominently increased scores of tubulointerstitial injury, interstitial collagen deposition, and protein expression of type I and type III collagen in ureter-obstructed kidneys, respectively. As compared with untreated rats, FD also significantly reduced the expression of α-SMA, TGF-ß(1), CTGF, PDGF, and inhibitor of TIMP-1 in the obstructed kidneys. Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy through its regulation on fibrogenic growth factors, tubular cell transdifferentiation, and extracellular matrix.