Chemiluminescent Conjugated Polymer Nanoparticles for Deep-Tissue Inflammation Imaging and Photodynamic Therapy of Cancer.

Deep-tissue optical imaging and photodynamic therapy (PDT) remain a big challenge for the diagnosis and treatment of cancer. Chemiluminescence (CL) has emerged as a promising tool for biological imaging and in vivo therapy. The development of covalent-binding chemiluminescence agents with high stability and high chemiluminescence resonance energy transfer (CRET) efficiency is urgent. Herein, we design and synthesize an unprecedented chemiluminescent conjugated polymer PFV-Luminol, which consists of conjugated polyfluorene vinylene (PFV) main chains and isoluminol-modified side chains. Notably, isoluminol groups with chemiluminescent ability are covalently linked to main chains by amide bonds, which dramatically narrow their distance, greatly improving the CRET efficiency. In the presence of pathologically high levels of various reactive oxygen species (ROS), especially singlet oxygen (1O2), PFV-Luminol emits strong fluorescence and produces more ROS. Furthermore, we construct the PFV-L@PEG-NPs and PFV-L@PEG-FA-NPs nanoparticles by self-assembly of PFV-Luminol and amphiphilic copolymer DSPE-PEG/DSPE-PEG-FA. The chemiluminescent PFV-L@PEG-NPs nanoparticles exhibit excellent capabilities for in vivo imaging in different inflammatory animal models with great tissue penetration and resolution. In addition, PFV-L@PEG-FA-NPs nanoparticles show both sensitive in vivo chemiluminescence imaging and efficient chemiluminescence-mediated PDT for antitumors. This study paves the way for the design of chemiluminescent probes and their applications in the diagnosis and therapy of diseases.

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

The Slow Growth of Adventitious Roots in Tetraploid Hybrid Poplar (Populus simonii × P. nigra var. italica) May Be Caused by Endogenous Hormone-Mediated Meristem Shortening.

Polyploidization produces abundant phenotypic variation. Little is currently known about adventitious root (AR) development variation due to polyploidization. In this study, we analyzed the morphological, cytological, and physiological variations in AR development between tetraploid and diploid Populus plants during in vitro rooting culture. Compared to the diploids, the AR formation times and rooting rates of the tetraploids' stem explants had non-significant changes. However, the tetraploid ARs exhibited significantly slower elongation growth than the diploid ARs. Cytological observation showed that the tetraploid ARs were characterized by shorter root meristems and reduced meristem cell numbers, suggesting the reasons for the slow AR elongation. Analysis of hormones and related metabolites during AR development demonstrated that the total auxin, cytokinin, and jasmonic acid contents were significantly lower in the tetraploid ARs than in those of the diploids, and that the ratio of total auxins to total CKs at 0 h of AR development was also lower in the tetraploids than in the diploids, whereas the total salicylic acid content of the tetraploids was consistently higher than that of the diploids. qPCR analysis showed that the expression levels of several hormone signaling and cell division-related genes in the tetraploid ARs significantly differed from those in the diploids. In conclusion, the slow elongation of the tetraploid ARs may be caused by the endogenous hormone-mediated meristem shortening. Our findings enhance the understanding of polyploidization-induced variation in AR development of forest trees.

Analysis of characteristics and changes in three-dimensional spatial and temporal distribution of aerosol types in Central Asia.

Atmospheric aerosol types and characteristics have regional and seasonal characteristics mainly due spatial and temporal differences in emission sources and diffuse transport conditions. We explored regional three-dimensional spatial and temporal distribution characteristics of aerosol types in Central Asia from daytime to nighttime by using long-term (2007-2021) CALIPSO lidar measurements. The three results are as follows: (1) Average aerosol optical depth (AOD) values during the 14 years were 0.44 and 0.47 during daytime and nighttime, respectively, with an overall decreasing trend, among which the AOD in spring in the southern border region and in winter in the northern border region showed high values, 0.66 and 0.31 during daytime and 0.69 and 0.33 during nighttime, respectively, and nighttime AOD values were higher than those of daytime, possibly due to the lower signal-to-noise ratio of the CALIPSO during the daytime than during the nighttime. (2) The primary representative aerosol type in the Taklamakan Desert region being pure sand and dust, and more apparent winter-polluted sand and dust exist along the northern slope of the Tianshan Mountains in Xinjiang in winter than in other areas. High-altitude soot mainly existed below 4 km and was primarily concentrated in northern Central Asia, with the highest values (0.016 and 0.003) in summer and winter, respectively, which may be due to different diffusion and transport conditions. (3) Dust aerosols in spring were mainly concentrated in the region of 2-6 km in the Taklamakan Desert area; pure dust particles in summer and fall lifted height diffusion and gradually moved to the northern border region; polluted dust was mainly in northern Xinjiang in fall and winter and spread to northern Central Asia; and the average top height of aerosols in the transmission process reached the top of the troposphere, and transmission height was higher than source area.

Interaction of 2D nanomaterial with cellular barrier: Membrane attachment and intracellular trafficking.

The cell membrane serves as a barrier against the free entry of foreign substances into the cell. Limited by factors such as solubility and targeting, it is difficult for some drugs to pass through the cell membrane barrier and exert the expected therapeutic effect. Two-dimensional nanomaterial (2D NM) has the advantages of high drug loading capacity, flexible modification, and multimodal combination therapy, making them a novel drug delivery vehicle for drug membrane attachment and intracellular transport. By modulating the surface properties of nanocarriers, it is capable of carrying drugs to break through the cell membrane barrier and achieve precise treatment. In this review, we review the classification of various common 2D NMs, the primary parameters affecting their adhesion to cell membranes, and the uptake mechanisms of intracellular transport. Furthermore, we discuss the therapeutic potential of 2D NMs for several major disorders. We anticipate this review will deepen researchers' understanding of the interaction of 2D NM drug carriers with cell membrane barriers, and provide insights for the subsequent development of novel intelligent nanomaterials capable of intracellular transport.

Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy.

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

An 8-18 GHz 90° Switched T-Type Phase Shifter.

This paper proposes a novel 8-18 GHz 90° switched T-type phase shifter (TPS). In contrast to the conventional TPS, the proposed TPS adds a compensation capacitance to greatly enhance the phase shifting capacity. Moreover, the designed structure also integrates a filtering compensation network, which can effectively achieve a flat relative phase shift in a wide band. The proposed 90° TPS is fabricated using 0.15 µm GaAs pHEMT technology. The TPS achieves homogeneous phase shift at 8-18 GHz, with the measured phase error of less than ±1.5°. The insertion loss of the proposed phase shifter is 1.3-2.6 dB, and the chip size is merely 0.53 × 0.86 mm2. Thanks to these excellent performance characteristics, the designed phase shifter is well-suited for ultra-wideband wireless communication and radar systems.

Influence of the ultra-fine fly ash dosages on the mechanical properties of the sulfoaluminate cement-based high water backfilling material.

To reduce the filling cost of high-water backfilling material (HWBM) in mining backfill and improve the recycling utilization of the industrial waste such as the coal fly ash. The ultra-fine fly ash (UFA) was added to the HWBM as a partial replacement in this work. Therefore, a series of experiments were performed to investigate the effect of UFA on the mechanical properties of the HWBM at the different curing conditions, then the hydration mechanism of the HWBM blended with UFA was analyzed by XRD and SEM method. The result indicates that the strength of the HWBM decreased with the increasing of UFA dosages, but the addition of UFA can improve the residual strength of the initial HWBM. Additionally, when the HWBM was cured at the laboratory air condition, its carbonation process was restrained obviously as the UFA dosages were less than 15% at the ages of 28 days, which indicates the UFA can improve the weathering resistance of the HWBM with the curing ages increasing effectively. The XRD and SEM results also shows that the degree of crystallinity of the HWBM increased when UFA dosages were less than 15% effectively, while there were few obvious changes on types of hydration products. It indicates that the main affects of UFA on the performance of HWBM is filler and dilution, which reduced the contact area between hydration products of HWBM and CO2 in the air, further improved the carbonation resistance of HWBM.

Research on the Healing Potential of Rural Community Streets From the Perspective of Audiovisual Integration: A Case Study of Four Rural Communities in China.

Rural communities have become a hot topic in academic circles because of their graceful natural environment and great healing potential. However, existing research still lacks attention to the street space in rural communities and rarely considers its integrated visual and soundscape design in terms of their effect on public health. As a result, the healing potential of rural community streets cannot be fully used in design practice. Relevant audiovisual materials were collected from a field investigation in four rural communities in southwestern China. Based on these data, the subjective and objective healing index data of subjects under comprehensive audiovisual conditions were collected and analyzed through laboratory experiments. The results revealed that type of street space affects healing potential, and the artificial-natural enclosed and natural semi-enclosed streets are the street types with the best healing effect. When the total sound pressure level was 55dB(A), the sound combination with birdsong accounting for 70% had a significant positive effect on improving the healing effect of rural community streets. In contrast, the sound combination with birdsong accounting for 50% or less had no significant effect on improving healing. The subjective healing perception of street space in rural communities was significantly positively correlated with aesthetic preferences. There was also a significant correlation between subjective healing perception and physiological index data in the audiovisual combination. This research explored the impact of different types of street space and sound combinations on the healing effect of rural community streets in an integrated audiovisual environment and provided a scientific basis for the healing landscape design of rural community streets in an integrated audiovisual environment. It was expected to provide new ideas for the construction of rural community landscapes, including acoustic landscapes, to promote physical and mental healing.

Correlation between Vegetation Structure and Species Diversity in Traditional Villages in Karst Topographic Regions of the Zunyi City, China.

Studying the relationship between vegetation structure and diversity is important in an area having karst topography and unique traditional customs. We selected a total of six traditional villages in Zunyi City, China, to collect vegetation data. Additionally, using one-way ANOVA and the Pearson correlation coefficient analytic method to analyze, the results showed that, overall, plant communities were mostly regularly distributed. The overall differentiation degree was low aggregation, intensity, and the extreme intensity mixed state. Overall, competitive pressure, growth vigor and stability were better than the natural forest. The community stability index at lower altitude was significantly higher than that at higher altitude. The recorded plant communities in the living space were typically aggregated, the plant communities were randomly distributed in the production space, and the plant communities were uniformly distributed in the ecological space. In general, the diversity indexes, except the Jh index, were the highest in the herb layer; the second was in the shrub layer and the lowest was in the tree layer. Species diversity at the middle altitude was higher than that at low and high altitudes (except for the shrub at a high altitude of 1100-1160 m). The overall plant species diversity was highest in the living space, second highest in the ecological space and lowest in the production space. On the whole, there was a significant correlation between the spatial structure of plant communities and the species diversity of plant communities at different altitudes, and in PLE spaces. The main objective of this study was to reveal the plant community structure, species diversity, and their relationship under the dual effects of national traditional culture and karst landform. Additionally, we sought to provide theoretical guidance for the construction of plant community protection and biodiversity conservation in traditional villages in karst areas.

Exploring the influence of residential courtyard space landscape elements on people's emotional health in an immersive virtual environment.

A good residential courtyard space not only brings people a psychological feeling of emotional pleasure but also attracts people to actively engage in more physical activities, which is of great significance to improving people's physical and mental health. Green vegetation and fitness facilities as the most preferred landscape elements in residential courtyard spaces and their effects on people's emotional health have not been further investigated. In this research, a virtual experiment was constructed in a residential courtyard space in Chengdu City, China, and electrodermal sensors were used to measure the real-time emotional changes of people in different virtual scenarios to analyze the effects of two landscape elements, green vegetation and fitness facilities, on people's emotional health, and the differences of such effects among different genders and ages. The results confirm that the combination of virtual reality technology and wearable physiological sensor measurement technology could effectively identify health-promoting landscape elements in urban environments; In residential courtyard spaces, green vegetation is more emotionally healthy than fitness facilities, and fitness facilities have better emotional health benefits for men and people over 30 years of age. The results of the study provide a quantitative basis for the healthier design and transformation of residential courtyard spaces for both green vegetation and fitness facilities.

The Mechanism of Important Components in Canine Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) is a potential treatment for many intestinal diseases. In dogs, FMT has been shown to have positive regulation effects in treating Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), canine parvovirus (CPV) enteritis, acute diarrhea (AD), and acute hemorrhagic diarrhea syndrome (AHDS). FMT involves transplanting the functional components of a donor's feces into the gastrointestinal tract of the recipient. The effective components of FMT not only include commensal bacteria, but also include viruses, fungi, bacterial metabolites, and immunoglobulin A (IgA) from the donor feces. By affecting microbiota and regulating host immunity, these components can help the recipient to restore their microbial community, improve their intestinal barrier, and induce anti-inflammation in their intestines, thereby affecting the development of diseases. In addition to the above components, mucin proteins and intestinal epithelial cells (IECs) may be functional ingredients in FMT as well. In addition to the abovementioned indications, FMT is also thought to be useful in treating some other diseases in dogs. Consequently, when preparing FMT fecal material, it is important to preserve the functional components involved. Meanwhile, appropriate fecal material delivery methods should be chosen according to the mechanisms these components act by in FMT.

A novel oncogenic enhancer of estrogen receptor-positive breast cancer.

Estrogen receptor-positive (ER+) breast cancer accounts for the majority of breast cancers diagnosed, and nearly 20% of patients do not respond to endocrine therapy. The pathogenesis of ER+ breast cancer has not been well elucidated. The enhancer is a cis-regulatory element that promotes gene transcription and plays an important role in the spatiotemporal expression of cellular genes. Nevertheless, the oncogenic enhancer and its role in the occurrence and progression of cancer remain unclear. Here, we report a novel oncogenic enhancer (named αE myc ) for c-Myc and reveal its activation mechanism in ER+ breast cancer. The results demonstrated that αE myc enhanced the transcription of downstream genes more than 20-fold. The deletion of the 7-bp region (GGTTGCA) in αE myc significantly downregulated the expression of c-Myc, resulting in cell nuclear changes, cell-cycle arrest, cell apoptosis, and finally, remarkable inhibition of cell proliferation. In conclusion, the present study discovers a novel oncogenic enhancer αE myc (801 base pairs [bp], at Chr8: 127668529-127669329) and offers a remarkable core enhancer target (GGTTGCA) of αE myc for gene therapy of ER+ breast cancer.

A density functional theory study on the electronic and adsorption characteristics of cyclo M9N9 (M = B and Al).

On the basis of experimental and theoretical calculations conducted for cyclo C18, we predicted two novel inorganic cyclo M9N9 (M = B and Al) molecules. Because of the significant difference in electronegativity between M and N atoms, M-N bonds were ionic. Furthermore, the interaction of cyclo M9N9 with cyclopropylpiperazine (CPPP) was investigated. In cyclo M9N9, each M atom could adsorb one CPPP molecule. The CPPP molecules exhibited a preference to remain outside cyclo M9N9 molecules. Depending on the structural characteristics of CPPP molecules, the exciting part is that up to four CPPP molecules could be adsorbed on the exterior surface of cyclo M9N9. We calculated adsorption energies and analyzed the main structural parameters in the process. The research results indicated that adsorption on cyclo Al9N9 was energetically more favorable than that on cyclo B9N9. The cyclo M9N9 have considerable potential in the future. Graphical abstract.

Expression of MMP-2 and TIMP-3 with incidence and prognosis of giant-cell tumor of the bone.

The expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) in giant-cell tumor of bone (GCT), and the correlation of their expression with the clinicopathologic features and prognosis were investigated. A total of 70 GCT patients treated in our hospital from September, 2013 to September, 2015, were selected, and the tumor and para-carcinoma tissues were obtained by surgery. The expression levels of MMP-2 and TIMP-3 in GCT and para-carcinoma tissues were detected via semi-quantitative polymerase chain reaction (PCR) and western blot analysis, as well as immunohistochemical staining. Moreover, the clinicopathological data of the GCT patients were collected to study the correlation of MMP-2 and TIMP-3 with clinicopathological features and prognosis of GCT. The results of semi-quantitative PCR and western blot analysis revealed that the expression level of MMP-2 in tissues of the 70 GCT patients was significantly higher than that in para-carcinoma tissues, and the difference was statistically significant (P<0.01), while the expression level of TIMP-3 was obviously lower than that in para-carcinoma tissues (P<0.01). The results of immunohistochemical staining revealed that the positive expression rate of MMP-2 was 57.6% in GCT tissues and 18.9% in para-carcinoma tissues, while that of TIMP-3 was 63.2% in GCT tissues and 13.8% in para-carcinoma tissues, and the differences were statistically significant (P<0.01). The expression levels of MMP-2 and TIMP-3 were correlated with the diameter of tumor, clinical staging, lymph node metastasis and relapse of GCT (P<0.01), but were not correlated with the age and sex of GCT patients (P>0.05). There was a negative correlation between MMP-2 and TIMP-3 expression levels (r=-0.258, P<0.05). The expression levels of MMP-2 and TIMP-3 are closely related to the clinicopathological features and prognosis of patients, which can be used as one of the clinical examination indexes of GCT and also provide new insights for the clinical treatment of GCT.

Mechanism of melatonin combined with calcium carbonate on improving osteoporosis in aged rats.

The effects of melatonin and calcium carbonate on aged rats with osteoporosis (OP) were assessed. Forty female Sprague-Dawley (SD) rats aged 15 months were randomly divided into a model group (group OP), melatonin group (group M), calcium carbonate group (group Ca) and melatonin combined with calcium carbonate group (group M+Ca), while 10 rats aged 3 months were set as the control group (group NC). The changes of bone density and bone mineral level of lumbar vertebra and bilateral femur in rats of each group were observed. The levels of serum calcium, phosphorus, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in rats of each group were determined. Compared with those in group NC, bone density of lumbar vertebra and bilateral femur and bone mineral level were distinctly reduced, serum calcium and activities of SOD and GSH-Px were obviously decreased, and MDA content was remarkably increased in rats of groups OP, M and Ca; the differences were statistically significant (P<0.05 or P<0.01); compared with that in group OP, bone density of lumbar vertebra and bilateral femur and bone mineral level were remarkably increased, serum calcium and activities of SOD and GSH-Px were obviously increased, and MDA content was remarkably decreased in rats of groups M, Ca and M+Ca; the differences were statistically significant (P<0.05 or P<0.01); compared with those in groups M and Ca, bone density of lumbar vertebra and bilateral femur and bone mineral level were obviously elevated, serum calcium and activities of SOD and GSH-Px were evidently elevated, and MDA content was remarkably decreased in rats of group M+Ca; the differences were statistically significant (P<0.05). Melatonin and calcium carbonate can significantly improve antioxidative ability in rats with osteoporosis, increase bone density, elevate serum calcium level and reduce bone mineral loss, thus preventing and treating osteoporosis, and the combination displays more remarkable effects.

Inhibitory effect of icariin on osteosarcoma cell proliferation via the Wnt/ß-catenin signaling pathway.

Osteosarcoma, is a kind of malignant tumor derived from malignant interstitial cells. The pathogenesis of osteosarcoma remains unclear and despite use of chemotherapy drugs, resistance to these drugs affects the success of treatment. The present study was conducted to investigate the effects of icariin (ICA) on osteosarcoma cell proliferation and to investigate the role of the Wnt/ß-catenin signaling pathway in the inhibition process of ICA on osteosarcoma cell proliferation. Different concentrations of ICA were selected to treat the osteosarcoma cell line 143B for 24 h, and then the onset concentration of ICA when it inhibited the growth of osteosarcoma cancer cell line 143B was detected via an MTT assay. The effect of ICA on the apoptosis of colon cancer cell line 143B under this concentration was detected using a flow cytometer. RNA in osteosarcoma cell line 143B was extracted, followed by reverse transcription. The expression levels of related and apoptotic proteins in the Wnt/ß-catenin signaling pathway using ICA were detected by semi-quantitative PCR and western blot analysis, respectively. The expression quantities of vascular endothelial growth factor (VEGF) and MMP-9 were detected by ELISA. MTT assay showed that ICA inhibited the growth of 143B when its concentration was 5 µM (p<0.01). Flow cytometry showed that the number of apoptotic cells after ICA treatment was significantly higher than that in control group (p<0.01). RNA in osteosarcoma cell line 143B was extracted, followed by reverse transcription. Semi-quantitative PCR and western blot analysis revealed that the expression levels of p-GSK3ß, ß-catenin, c-Myc and cyclin D1 in cells after ICA treatment were significantly downregulated (p<0.01), while the expression level of caspase-3 was significantly increased (p<0.01). ELISA showed that the expression quantities of VEGF and MMP-9 were significantly decreased (p<0.01). Thus, ICA can significantly inhibit osteosarcoma cell proliferation and promote osteosarcoma cell apoptosis, which may be realized by affecting the expression of the Wnt/ß-catenin signaling pathway and blocking the expression of related proteins.

Inhibitor of growth 3 induces cell death by regulating cell proliferation, apoptosis and cell cycle arrest by blocking the PI3K/AKT pathway.

ING3 is a potential candidate tumor-suppressor gene that has been implicated in the pathogenesis of various cancers, however the exact role and mechanism of ING3 in gastric cancer (GC) remains elusive. In this study, the low expression of ING3 was validated in GC tissues and various GC cell lines. Overexpression of ING3 by transfection with pEGFP-ING3 plasmids inhibited cell proliferation in SGC-7901 and BGC-825 cells, concomitant with the decrease in the expression of PCNA, a marker for cell proliferation. Furthermore, overexpression of ING3-induced cell cycle arrest at G2/M phase. Meanwhile, elevation of ING3 distinctly aggravated cell apoptosis and increased Bax and Caspase-3 expression, but decreased Bcl-2 expression. Moreover, ING3 upregulation inhibited the activation of the PI3K/AKT pathway by reducing the expressions of p-PI3K and p-Akt in GC cells. Notably, preconditioning with IGF-1, a PI3K/Akt agonist, reversed the suppressive effects of ING3 overexpression on GC cell growth, cell cycle arrest and apoptosis. Furthermore, IGF-1 attenuated the inhibitory effect of excessive ING3 on CyclinD1 expression. Taken together, these results suggest ING3 may function as a tumor-suppressor gene in the progression of GC. Therefore, ING3 could serve as a potential therapeutic strategy for the treatment of GC.

Association between the expression of inhibitor of growth family member 4 and the progression of clear cell renal carcinoma.

Inhibitor of growth family member 4 (ING4) is a candidate tumor suppressor that serves important roles in tumor growth and angiogenesis. In the present study ING4 expression was assessed in clear cell renal carcinoma (CCRC) tissues and its association with the progression of CCRC was determined. The expression of ING4 in 125 patients with CCRC was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemical methods. A total of 40 adjacent normal renal tissues were used as control samples. The results identified that ING4 expression was positive in 100% of normal renal tissues, but in only 82.3% CCRC samples. RT-qPCR and western blotting results demonstrated that expression levels of ING4 mRNA and protein were significantly decreased in CCRC compared with in normal tissues (P<0.0001). ING4 expression was not associated with sex, age or tumor volume (P>0.05), but was associated with the nuclear grade of renal cancer (P<0.0001), the clinical stage of CCRC (P<0.0001) and lymphatic metastasis (P<0.0001). The results of the present study indicated that dysregulation of ING4 expression may be involved in the initiation and progression of CCRC.