Aloin alleviates corneal injury in alkali burn via inhibiting neutrophil extracellular traps and promoting Nrf2.

OBJECTIVE: Ocular chemical burns are a leading cause of blindness. The cornea is injured by alkali-induced oxidative disturbances and an inflammatory response. The aim of this study was to evaluate the protective effects of aloin, an antioxidant, and anti-inflammatory compound, on corneal alkali burn. MATERIALS AND METHODS: Mice eyes were injured by NaOH and subsequently treated with aloin eye drop and intraperitoneal injection. Pathological characteristics of the eyes were examined, and corneal samples were collected for further analysis. RESULTS: Aloin diminished neutrophil infiltration and the production of proinflammatory cytokines. Aloin also attenuated apoptosis in human corneal epithelial cells (HCEs) by reducing oxidative stress through the activation of the Nrf2 pathway. Additionally, aloin suppressed the formation of neutrophil extracellular traps (NETs) and inhibited their deposition on the cornea. Moreover, aloin mitigated alkali-induced apoptosis in HCEs caused by NETs. CONCLUSIONS: These findings suggest that aloin has potential as an antioxidant and anti-inflammatory compound for treating corneal alkali burn by inhibiting NETs formation and promoting Nrf2.

Hip effusion/synovitis influences results after multiple drilling core decompression for bone marrow edema syndrome of hip.

BACKGROUND: At present, it is not known whether hip effusion/synovitis affects the therapeutic effect of multiple drilling core decompression (MDCD) in patients with bone marrow edema syndrome of hip (BMESH). The aims were to assess hip effusion/synovitis and its relationship with results of MDCD in patients with BMESH. METHODS: The data of undergoing arthroscopic-assisted MDCD for treatment of BMESH with hip effusion/synovitis by one surgeon were retrospectively reviewed from the associated medical records at the Affiliated Hospital of Zunyi Medical University (2016-2019). Seven patients (9 hips) participated in this study. Patients were followed up at 1, 2, 3, 6, 12 and 24 months. Data included demographics and clinical outcomes. The pre- and postoperative pain and functional outcomes were measured with the visual analogue scale (VAS), Harris Hip Score (HHS), Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), International Hip Outcome Tool-12 (iHOT-12) and range of motion (ROM). RESULTS: Seven patients (9 hips) were followed up. Disappearance of hip pain immediately obtained at rest after surgery. All of 7 patients returned to their former activity level at postoperative 3 months, bone marrow edema had disappeared on Magnetic Resonance Imaging (MRI). The VAS, HHS, HOS-ADL, iHOT-12, and ROM at postoperative 1 month had a significant difference (P < 0.05) compared with preoperative. It was also statistically significant (P < 0.05) when compared with other time points. At the final follow-up, all patients had no limited ROM, which was symmetrical with the contralateral of hip joint. Hip effusion/synovitis were observed in 9 hips. Labral tears, cartilage fissure, and loose bodies were observed in 1 hip, respectively. Kirschner wire tracks bleeding occurred in 1 hip. No other complications occurred. CONCLUSIONS: Hip effusion/synovitis could affect the clinical outcomes after MDCD in patients with BMESH. Arthroscopic procedure of hip effusion/synovitis can shorten postoperative pain relief time, disappearance time of bone marrow edema on MRI. It can simultaneously diagnose and treat other concomitant intraarticular pathologies, and be a safe operation with fewer complications.

Generation of an Ihh-mKate2-Dre knock-in mouse line.

Indian hedgehog (Ihh), a member of the Hh family, plays important roles in vertebrate development and homeostasis. To improve our understanding of the function of Ihh-expressing cells and their progeny as well, we generate an Ihh-mKate2tomm20 -Dre knock-in mouse line that can label Ihh-positive cells with a fluorescence protein mKate2 and trace Ihh-positive cells and their progeny via Dre-mediated recombination. Consistent with previous reports, we verified Ihh expression in hypertrophic chondrocytes of growth plate and granulosa cells of ovarian follicles by mKate2 immunostaining, and meanwhile confirmed Dre activity in these cells via a Dre reporter mouse line Rosa26-confetti2. We also found, for the first time, that Ihh can mark some cell types, including retinal ganglion cells, Purkinje cells, and gallbladder epithelial cells. Taken together, the Ihh-mKate2tomm20 -Dre mouse is a genetic tool for examining the precise expression profile of Ihh and tracing Ihh-expressing cells and their progeny.

Efficacy evaluation and mechanism study on inhibition of breast cancer cell growth by multimodal targeted nanobubbles carrying AMD070 and ICG.

To construct targeted nanobubbles carrying both small-molecule CXCR4 antagonist AMD070 and light-absorbing material indocyanine green (ICG), and to study their in vitro multimodal imaging, as well as their mechanism and efficacy of inhibition of breast cancer cell growth. Nanobubbles carrying AMD070 and ICG (ICG-TNBs) were constructed by carbodiimide reaction and mechanical oscillation. The physical characteristics and in vitro multimodal imaging were determined. The binding potential of ICG-TNBs to human breast cancer cells were observed by laser confocal microscopy. CCK-8 and flow cytometry were used to analyze the role of ICG-TNBs + US in inhibiting proliferation and inducing apoptosis of tumor cells. Flow cytometry and Western blotting are used to analyse the ROS generation and molecular mechanisms. ICG-TNBs had a particle size of 497.0 ± 29.2 nm and a Zeta potential of -8.05 ± 0.73 mV. In vitro multimodal imaging showed that the image signal intensity of ICG-TNBs increased with concentration. Targeted binding assay confirmed that ICG-TNBs could specifically bind to MCF-7 cells (CXCR4 positive), but not to MDA-MB-468 cells (CXCR4 negative). CCK-8 assay and flow cytometry analysis showed that ICG-TNBs + US could significantly inhibit the growth of MCF-7 breast cancer cells and promote their apoptosis. Flow cytometry and Western blotting showed that ICG-TNBs + US could significantly raise generation of ROS, reduce the expression of CXCR4, inhibit phosphorylation of Akt, and increase the expression of Caspase3 and Cleaved-caspase3. This indicated that ICG-TNBs could effectively inhibit and block the SDF-1/CXCR4 pathway, thus leading to the apoptosis of MCF-7 cells. ICG-TNBs can specifically bind to CXCR4 positive breast cancer cells, furthermore inhibit growth and promote apoptosis of breast cancer cells combined with ultrasonic irradiation by blocking the SDF-1/CXCR4 pathway. This study introduces a novel concept, method and mechanism for integration of targeted diagnosis and treatment of breast cancer.

Multifunctional nanobubbles carrying indocyanine green and paclitaxel for molecular imaging and the treatment of prostate cancer.

BACKGROUND: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours. RESULTS: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and - 21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 2.52%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs + US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs + US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs + US groups. CONCLUSIONS: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.

miR-106a promotes cardiac hypertrophy by targeting mitofusin 2.

Pathological cardiac hypertrophy is a main factor leading to heart failure and associated sudden death. Improved understanding of the underlying molecular mechanisms should aid better treatment of the disease. This study aimed to test our hypothesis that a microRNA miR-106a played an important role in the development of cardiac hypertrophy through targeting mitofusin 2 (Mfn2), a mitochondrial fusion protein known to be critical in regulating cardiac function. miR-106a was robustly upregulated in hypertrophied myocardium both in vivo and in vitro. Forced transient expression of miR-106a in otherwise healthy cardiomyocytes induced the hypertrophic phenotypes resembling those produced by angiotensin II (AngII) exposure. Knockdown of miR-106a by its specific inhibitor nearly completely reversed the hypertrophic phenotypes induced by AngII pretreatment and pressure overload. On the other hand, Mfn2 was markedly downregulated in hypertrophic heart and cardiomyocytes, which was in reciprocal to expression of miR-106a. Mfn2 was experimentally validated as a direct target gene for miR-106a. Overexpression of Mfn2 counteracted the hypertrophic responses induced by miR-106a, whereas silence of Mfn2 by its siRNA abolished the anti-hypertrophic property of miR-106a inhibitor. Furthermore, overexpression of Mfn2 alleviated the hypertrophic phenotypes induced by AngII in cultured cardiomyocytes, while Mfn2 siRNA alone was able to induce hypertrophic changes in cultured cardiomyocytes. Moreover, AngII and miR-106a treatment cultured cardiomyocytes mitochondria presented cristae defects, considerable depolarization of mitochondrial membrane and increased ROS production. These alterations were reversed by miR-106a inhibitor or overexpression of Mfn2. Taken together, our findings indicate miR-106a as an important factor to promote hypertrophic progress and suggest miR-106a as a new molecular target for the treatment of pathological hypertrophy. The present study also uncovered a novel relationship between miR-106a and Mfn2, with Mfn2 as a downstream signaling mediator of miR-106a.

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma.

BACKGROUND/AIMS: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. METHODS: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. RESULTS: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. CONCLUSION: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.

[Variation and correlation analysis on phenotypic traits of Scutellaria baicalensis from different strains].

To research the differences and correlation between Scutellaria baicalensis about phenotypic traits of different strains, 10 aboveground traits and 6 root traits of S. baicalensis in two-year-transplanted plants from 14 different strains were compared respectively, and the SPSS 17.0 statistical software was used for data analysis. It showed that phenotypic traits variation of different S. baicalensis strains was rich and the F value ranged from 3.169 to 71.58. The difference was significant between each other and germplasm 15 performs the most outstanding characters. Correlation analysis showed that there existed a significant correlation between the characters except for lateral root number, root diameter and length. The correlation coefficient between the fresh weight of root and the reed head diameter was up to 0.877. Principal component analysis showed that the average of overall yield per plant and root diameter could be used as the comprehensive reference index for germplasm evaluation. The differences and correlations in phenotypic traits of different S. baicalensis strains, provide theoretical basis for distinguishing germplasm and breeding good varieties of S. baicalensis.

The relationship between refractive error and the risk of diabetic retinopathy: a systematic review and meta-analysis.

Purpose: This meta-analysis was conducted to collect all available data and estimate the relationship between refractive error and the risk of diabetic retinopathy (DR) in patients with diabetes, and to assess whether vision-threatening DR (VTDR) is associated with refractive error. Methods: We systematically searched several literature databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, CBM, Wan Fang Data, and VIP databases. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed or random effects models. Four models were developed to assess the relationship between refractive error and the risk and DR, VTDR: hyperopia and DR, VTDR; myopia and DR, VTDR; spherical equivalent (SE per D increase) and DR, VTDR; and axial length (AL per mm increase) and DR, VTDR. The included literature was meta-analyzed using Stata 12.0 software, and sensitivity analysis was performed. Publication bias in the literature was evaluated using a funnel plot, Begg's test, and Egger's test. Results: A systematic search identified 3,198 articles, of which 21 (4 cohorts, 17 cross-sectional studies) were included in the meta-analysis. Meta-analysis showed that hyperopia was associated with an increased risk of VTDR (OR: 1.23; 95% CI: 1.08-1.39; P = 0.001), but not with DR (OR: 1.05; 95% CI: 0.94-1.17; P = 0.374). Myopia was associated with a reduced risk of DR (OR: 0.74; 95% CI: 0.61-0.90; P = 0.003), but not with VTDR (OR: 1.08; 95% CI: 0.85-1.38; P = 0.519). Every 1 diopter increase in spherical equivalent, there was a 1.08 increase in the odds ratio of DR (OR: 1.08; 95% CI: 1.05-1.10; P<0.001), but not with VTDR (OR: 1.05; 95% CI: 1.00-1.10; P = 0.06). AL per mm increase was significantly associated with a decreased risk of developing DR (OR: 0.77; 95% CI: 0.71-0.84; P<0.001) and VTDR (OR: 0.63; 95% CI: 0.56-0.72; P<0.001). Analysis of sensitivity confirmed the reliability of the study's findings. Conclusion: This meta-analysis demonstrates hyperopia was associated with an increased risk of VTDR in diabetes patients. Myopia was associated with a reduced risk of DR. AL is an important influencing factor of refractive error. Every 1 mm increase in AL reduces the risk of DR by 23% and the risk of VTDR by 37%. Systematic review registration: identifier: CRD42023413420.

Effects of wearing myopia glasses on eye movement and scleral blood supply.

The present study examined the effect of wearing myopia glasses on eye movement and scleral blood supply. For this purpose, a total of 30 individuals were recruited for the present self-control study. Under the same fixation distance, the individuals wore 0.00 D and -10.00 D glasses. The amount of eye movement generated when shifting from gazing at a central point to a point light source located at the left or right was measured and compared between the two glasses. The results revealed that the range of eye movement was significantly reduced after wearing -10.00 D glasses. When gazing at the right point light source from the central point, the difference between the rotation distances of the right eye when wearing the 0.00 D glasses and the -10.0 D glasses was 0.73±0.45 mm (t=8.93, P<0.01) and that of the left eye was 0.73±0.43 mm (t=9.34, P<0.01). Similar results were obtained when the left point light source was viewed from a shift in gaze from the central point. On the whole, the present study demonstrates that wearing concave lenses limits eyeball movement. Restricted eyeball movement can affect vascular changes within the extraocular muscles and blood flow, thereby affecting the blood supply to the anterior segment and sclera of the eye, potentially accelerating the development of myopia.

Effects of nitrogen fertilizer application on the physicochemical properties of foxtail millet (Setaria italica L.) starch.

The use of nitrogen fertilizer is a crucial agronomic practice to increase crop output and quality. This study investigated the impact of five nitrogen application levels (0, 60, 135, 210, and 285 kg N/hm2) on the physicochemical properties of foxtail millet (FM) starch. Optimal nitrogen application (210 kg N/hm2) significantly increased L*, a*, and b* values, water and oil absorption capacity, water solubility, and swelling power of starch. The number of small starch granules increased as the nitrogen application rate increased, but the granule morphology and typical A-type pattern did not change among the treatments. Nitrogen application increased the relative crystallinity and ordered structure, resulting in a higher gelatinization enthalpy. Compared to the control group (7.02 J/g), the enthalpy increased by 21.94 %, 66.38 %, 73.50 %, and 103.28 % under the nitrogen application rates, respectively. Moreover, nitrogen application greatly increased the percentage of A and B3 chains while it lowered the apparent amylose content, peak viscosity, and final viscosity. The effects of 210 and 285 kg N/hm2 treatments on the water solubility and swelling power, water and oil absorption, and light transmission of starch were greater compared to the 60 and 135 kg N/hm2 treatments. These results indicate that nitrogen fertilization significantly affects the physicochemical properties of FM starch.

Visual outcomes of combined use of implantable collamer lens implantation and laser corneal visual correction for myopia over -18.00 diopters.

PURPOSE: To explore visual outcomes in patients with extreme myopia receiving an implantable collamer lens (ICL) at -18.00 diopters (D), with central port, followed by bioptics by laser vision correction (laser in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]) to address residual myopia or myopic astigmatism. SETTING: Clínica Baviera (Aier Eye Hospital Group), Bilbao, Spain. DESIGN: Retrospective analysis of cases. METHODS: The study assessed uncorrected distance visual acuity, corrected distance visual acuity (CDVA), predictability, safety, efficacy, and patient satisfaction after implantation of the ICL and bioptics. The model implanted was V4c and EVO, with a correction of -18.00 D. Bioptics were performed at least 3 months after implantation, and patients were followed up for at least 3 months after LASIK or PRK. RESULTS: The analysis included 125 eyes from 90 patients. Of these, 51.2% underwent LASIK and 48.8% PRK. Mean time from implantation to bioptics was 5.9 ± 9.4 months. Patients were followed up for a mean of 40.2 ± 37.9 months after bioptics. Median manifest refractive spherical equivalent was -2.89 D before bioptics and -0.49 D after. Median CDVA was 0.18 logMAR before bioptics and 0.17 after. The mean safety and efficacy indices were 2.22 ± 1.88 and 2.06 ± 1.85, respectively. CONCLUSIONS: Visual outcomes and safety indices after ICL implantation and subsequent LASIK or PRK in patients with extreme myopia are excellent.

Identification of severe fever with thrombocytopenia syndrome virus isolates in the northwest of Hubei Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease that is increasingly affecting human being worldwide. The clinical manifestations and mortality rates of SFTS can vary depending on the geographic region and the specific genotype of the SFTS virus (SFTSV). From July 2022 to August 2023, we collected serum samples from 83 patients with suspected SFTSV infection in the northwest of Hubei Province, China. From which, 13 patients tested positive for SFTSV. Phylogenetic analysis of the SFTSV L, M, and S gene segments was performed using the maximum likelihood method to determine the genetic diversity of the isolates. At least 2 SFTSV genotypes (A and F) were identified in the northwest of Hubei Province. The clinical manifestations and laboratory findings on the first day of admission were investigated. Results showed that bleeding and disturbance of consciousness, and significant elevated AST and APTT, are valuable for assessing the prognosis for SFTS patients. This study disclosed the genomic sequences and genotypes of SFTSV spreading in the northwest of Hubei Province for the first time, providing information of genetically etiology for SFTS in the local district. Furthermore, certain symptoms and/or laboratory findings may indicate adverse clinical outcomes, highlighting the importance of identifying the symptoms and monitoring specific laboratory markers. Future research is needed to investigate the threshold values of these markers and to closely observe the indicative symptoms in order to early identify and timely management of critically ill patients within clinical settings.

The role of cytoreductive radical prostatectomy and lymph node dissection in bone-metastatic prostate cancer: A population-based study.

BACKGROUNDS: The role of cytoreductive radical prostatectomy (cRP) for bone-metastatic prostate cancer (bmPCa) remains controversial. We aimed to figure out whether cRP and lymph node dissection (LND) can benefit bmPCa. METHODS: 11,271 PCa patients with bone metastatic burden from 2010 to 2019 were identified using SEER-Medicare. Overall survival (OS) and cancer-specific survival (CSS) rates were visualized using Kaplan-Meier plots. Multivariable Cox regression analyses were constructed to examine the effects of cRP and LND on survival, after stratifying to age, prostate specific antigen (PSA), clinical stages, Gleason score, metastatic burden, radiotherapy, and chemotherapy status. RESULTS: 317 PCa patients underwent cRP and cRP was increasingly performed for bmPCa from 2010 (2.2%) to 2019 (3.0%) (p < 0.05). In multi analyses, cRP was predisposed to a better OS or CSS in patients with age < 75, PSA < 98 ng/mL, bone-only metastatic sites or patients not receiving chemotherapy (all p < 0.05). For the patients undergoing cRP, LND especially extended LND was associated with a better OS or CSS (all p < 0.05). CONCLUSIONS: cRP might benefit OS or CSS in young patients with low PSA and bone-only metastatic sites not receiving chemotherapy. And a clear OS or CSS benefit of LND especially extended LND was observed in patients undergoing cRP.

[Spatial and temporal expression pattern of somatostatin receptor 2 in mouse].

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.

Poor accuracy of single serological IgM tests in children with suspected acute Mycoplasma pneumoniae infection in Guangzhou, China.

Introduction. Early and accurate diagnosis of Mycoplasma pneumoniae (MP) infection of children with pneumonia is at the core of treatment in clinical practice.Gap Statement. Serological immunoglobulin M (IgM) tests for MP infection of children in south China have been rarely described.Aim. To assess the diagnostic performance and clinical application of serodiagnosis of MP infection in paediatric pneumonia patients.Methodology. Serum samples from 144 children diagnosed with MP pneumonia were subjected to a particle agglutination (PA)-based IgM assay. Meanwhile, we used an established suspension array as the reference standard method for the detection of MP DNA in bronchoalveolar lavage fluid (BALF) from all patients to assess the reliability of serological assays.Results. When running immunological testing in single serum samples, 80.6 %(79/98) of cases were diagnosed with MP infection, whereas only 55 (56.1 %) cases were positive in MP DNA analysis. Furthermore, single serum tests for IgM during acute MP infection resulted in 85.5 % (47/55) sensitivity and 25.6 % (11/43) specificity. Nevertheless, immunological testing and MP DNA analysis yielded the same results when paired sera were available for MP IgM antibody testing.Conclusion. Paired serological IgM assays are necessary for the determination of an acute MP infection, whereas single serological IgM testing is unreliable. Moreover, even a short interval of two MP serological tests works well.

PRMT5 acts as a tumor suppressor by inhibiting Wnt/ß-catenin signaling in murine gastric tumorigenesis.

Previous studies have demonstrated the in vitro oncogenic role of protein arginine methyltransferase 5 (PRMT5) in gastric cancer cell lines. The in vivo function of PRMT5 in gastric tumorigenesis, however, is still unexplored. Here, we showed that Prmt5 deletion in mouse gastric epithelium resulted in spontaneous tumorigenesis in gastric antrum. All Prmt5-deficient mice displayed intestinal-type gastric cancer within 4 months of age. Of note, 20% (2/10) of Prmt5 mutants finally developed into invasive gastric cancer by 8 months of age. Gastric cancer caused by PRMT5 loss exhibited the increase in Lgr5+ stem cells, which are proposed to contribute to both the gastric tumorigenesis and progression in mouse models. Consistent with the notion that Lgr5 is the target of Wnt/ß-catenin signaling, whose activation is the most predominant driver for gastric tumorigenesis, Prmt5 mutant gastric cancer showed the activation of Wnt/ß-Catenin signaling. Furthermore, in human gastric cancer samples, PRMT5 deletion and downregulation were frequently observed and associated with the poor prognosis. We propose that as opposed to the tumor-promoting role of PRMT5 well-established in the progression of various cancer types, PRMT5 functions as a tumor suppressor in vivo, at least during gastric tumor formation.

Enhanced stable luminescence and photochemical properties of ruthenium complex/zirconium phosphate hybrid assemblies.

The luminescent metal complex Ru(bpy)3Cl2.6H2O was directly intercalated into Zr(HPO4)2.6H2O nano-lamellar framework and characterized with respect to its optical and photochemical properties. The incorporation of the complex within the inorganic framework expands the interlayer distance from 10.4 to 15.2 A, and forms complex/framework hybrid assemblies. Upon binding to the framework, the metal-to-ligand charge transfer absorption of the complex is red-shifted from 452 to 462 nm, and the maximum emission is blue-shifted from 610 to 604 nm. The luminescence intensity of the complex/framework suspensions increases more than 2-fold as compared to aqueous solutions. The sub-micrometer (0.2-0.3 microm) particles of the hybrid assemblies result in the luminescence intensity of the suspensions quite stable. In addition, the excited state of Ru(bpy)3(2+) was photochemical quenched by Fe(CN)6(3-), and the Stern-Volmer results reveal that most Ru(bpy)3(2+) cations have entered into the layer of the framework.

Preparation Of Nanobubbles Modified With A Small-Molecule CXCR4 Antagonist For Targeted Drug Delivery To Tumors And Enhanced Ultrasound Molecular Imaging.

PURPOSE: To construct nanobubbles (PTX-AMD070 NBs) for targeted delivery of paclitaxel (PTX) and AMD070, examine their performance in ultrasound molecular imaging of breast cancer and cervical cancer and their therapeutic effect combined with ultrasound targeted nanobubble destruction (UTND). MATERIALS AND METHODS: PTX-AMD070 NBs were prepared via an amide reaction, and the particle size, zeta potential, encapsulation rate and drug loading efficiency were examined. Laser confocal microscopy and flow cytometry were used to analyze the targeted binding ability of PTX-AMD070 NBs to CXCR4+ MCF-7 cells and C33a cells. The effect of PTX-AMD070 NBs combined with UTND on cell proliferation inhibition and apoptosis induction was detected by CCK-8 assays and flow cytometry. The contrast-enhanced imaging features of PTX-AMD070 NBs and paclitaxel-loaded nanobubbles were compared in xenograft tumors. The penetration ability of PTX-AMD070 NBs in xenograft tissues was evaluated by immunofluorescence. The therapeutic effect of PTX-AMD070 NBs combined with UTND on xenograft tumors was assessed. RESULTS: PTX-AMD070 NBs showed a particle size of 494.3±61.2 nm, a zeta potential of -22.4±1.75 mV, an encapsulation rate with PTX of 53.73±7.87%, and a drug loading efficiency with PTX of 4.48±0.66%. PTX-AMD070 NBs displayed significantly higher targeted binding to MCF-7 cells and C33a cells than that of PTX NBs (P<0.05), and combined with UTND manifested a more pronounced effect in inhibiting cell proliferation and promoting apoptosis than other treatments. PTX-AMD070 NBs aggregated specifically in xenograft tumors in vivo, and significantly improved the image quality. Compared with other treatment groups, PTX-AMD070 NBs combined with UTND exhibited the smallest tumor volume and weight, and the highest degree of apoptosis and necrosis. CONCLUSION: PTX-AMD070 NBs improved the ultrasound imaging effect in CXCR4+ xenograft tumors and facilitated targeted therapy combined with UTND. Therefore, this study provides an effective method for the integration of ultrasound molecular imaging and targeted therapy of malignant tumors.

Optical properties of porphyrin chromophores assembled in nano-lamellar zirconium phosphate.

The supra-molecular assemblies and optical properties of the symmetrical neutral porphyrin chromophore, meso-tetra(4-pyridyl)porphine, bound to a modified alpha-zirconium phosphate framework have been studied. The interlayer distance of the cetyltrimethylammonium zirconium phosphate framework is 39.6 angstroms. After the addition of meso-tetra(4-pyridyl)porphine to the framework, the X-ray powder diffraction (XRPD) patterns show that the interlayer distance of the framework is 30.3 angstroms, demonstrating the formation of novel assemblies. In the framework, organic chromophores are assumed to align in a canted monolayer. The interaction of organic chromophores with the framework causes noticeable red shifts of the Soret absorption band from 416 to 427 nm. In contrast, the luminescence peak is blue shifted from 660 nm in aqueous media to 648 nm when meso-tetra(4-pyridyl)porphine is bound to the framework. Furthermore, the emission yield of the organic chromophore in the framework is dramatically enhanced compared to that of organic aqueous solutions. The spectroscopic change of meso-tetra(4-pyridyl)porphine is ascribed to the unique microenvironments of the nano-lamellar framework. The juxtaposition of the porphyrin chromophores in the framework tunes their electronic interactions. In comparison, the organic chromophores also attempted to bind with another modified alpha-zirconium phosphate, n-butylammonium zirconium phosphate. However, the chromophores could not enter into n-butylammonium zirconium phosphate due to its smaller interlayer distance (18.8 angstroms).