[Expression of CD30 in Patients with Diffuse Large B-Cell Lymphoma and Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of CD30 in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on 124 cases of primary DLBCL diagnosed at Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2018 to July 2020. The expression of CD30 in patients with DLBCL was detected by immunohistochemical method, and the clinicopathological characteristics were analyzed and compared between CD30+ and CD30- groups. Kaplan-Meier analysis was used for survival analysis. The relationship between CD30 expression and clinical features and prognosis were analyzed. RESULTS: Among the 124 patients with DLBCL, 19 patients expressed CD30, and the positive rate is 15.32%. The clinico-pathological characteristics of CD30+ in patients with DLBCL were characterized by low age, more common in males, fewer extranodal lesions, lower international prognostic index (IPI), GCB type being more common in Hans subtype, and achieving better therapeutic effects (P < 0.05). However, there were no significant statistical differences in B-symptoms (P =0.323), Ann Arbor staging (P =0.197), Eastern Cooperative Oncology Group (ECOG) score (P =0.479), lactate dehydrogenase (LDH) (P =0.477), and the involvement of bone marrow (P =0.222). There were significant differences in OS and PFS between the CD30+ and CD30- groups (χ2=5.653, P =0.017; χ2＝4.109，P =0.043), the CD30+ group had a better prognosis than that of the CD30- group. The results of subgroup analysis showed that the CD30+ group in the IPI score=1-2, LDH elevated group had a better prognosis (P < 0.05). In the subgroups of Ann Arbor staging III-IV (P =0.055) and non GCB type (P =0.053), the CD30+ group had a good prognosis trend, but the difference was not statistically significant. The results of univariate analysis showed that the good prognosis of DLBCL patients was closely related to CD30+ expression, no B-symptoms, early Ann Arbor staging, low ECOG score, normal LDH, low IPI score, fewer extranodal involvement, and obtaining the best therapeutic effect as CR (all P <0.05). COX multivariate regression analysis showed that the presence of B-symptoms and achieving the best therapeutic effect as Non-CR were independent risk factors affecting the prognosis of DLBCL patients (P < 0.05). CONCLUSION: The CD30+ expression in DLBCL patients indicates a good prognosis and has certain diagnostic value in evaluating the prognosis of DLBCL patients.

Application status and optimization suggestions of tumor organoids and CAR-T cell co-culture models.

Tumor organoids, especially patient-derived organoids (PDOs) exhibit marked similarities in histopathological morphology, genomic alterations, and specific marker expression profiles to those of primary tumour tissues. They are applied in various fields including drug screening, gene editing, and identification of oncogenes. However, CAR-T therapy in the treatment of solid tumours is still at an exploratory stage. Tumour organoids offer unique advantages over other preclinical models commonly used for CAR-T therapy research, which the preservation of the biological characteristics of primary tumour tissue is critical for the study of early-stage solid tumour CAR-T therapies. Although some investigators have used this co-culture model to validate newly targeted CAR-T cells, optimise existing CAR-T cells and explore combination therapy strategies, there is still untapped potential in the co-culture models used today. This review introduces the current status of the application of tumour organoid and CAR-T cell co-culture models in recent years and commented on the limitations of the current co-cultivation model. Meanwhile, we compared the tumour organoid model with two pre-clinical models commonly used in CAR-T therapy research. Eventually, combined with the new progress of organoid technologies, optimization suggestions were proposed for the co-culture model from five perspectives: preserving or reconstructing the tumor microenvironment, systematization, vascularization, standardized culture procedures, and expanding the tumor organoids resource library, aimed at assisting related researchers to better utilize co-culture models.

Preparation of surface molecular imprinting fluorescent sensor based on magnetic porous silica for sensitive and selective determination of catechol.

A magnetic fluorescent molecularly imprinted sensor was successfully prepared and implemented to determine catechol (CT). Fe3O4 nanoparticles were synthesized by the solvothermal technique and mesoporous Fe3O4@SiO2@mSiO2 imprinted carriers were prepared by coating nonporous and mesoporous SiO2 shells on the surface of the Fe3O4 subsequently. The magnetic surface molecularly imprinted fluorescent sensor was created after the magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane to introduce double bonds on the surface of the carries and the polymerization was carried out in the presence of CT and fluorescent monomers. The magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane and double bonds were introduced on the surface of the carriers. After CT binding with the molecularly imprinted polymers (MIPs), the fluorescent intensity of the molecularly imprinted polymers (Ex = 400 nm, Em = 523 nm) increased significantly. The fluorescent intensity ratio (F/F0) of the sensor demonstrated a favorable linear correlation with the concentration of CT between 5 and 50 µM with a detection limit of 0.025 µM. Furthermore, the sensor was successfully applied to determine CT in actual samples with recoveries of 96.4-105% and relative standard deviations were lower than 3.5%. The results indicated that the research of our present work provided an efficient approach for swiftly and accurately determining organic pollutant in water.

Corrigendum: Peroxisome proliferator-activated receptor-α: A pivotal regulator of the gastrointestinal tract.

[This corrects the article DOI: 10.3389/fmolb.2022.864039.].

Comparison of the psychoactive activity of four primary Areca nut alkaloids in zebrafish by behavioral approach and molecular docking.

Areca palm nut (Areca catechu) has been listed as one of the most addictive substances, along with tobacco, alcohol, and caffeine. It belongs to the family Arecaceae and is widely used in Asia. Areca nut contains seven psychoactive alkaloids; however, the effects of these alkaloids on behaviors are rarely to be addressed in zebrafish. Therefore, this study aims to compare the psychoactive and potential adverse effects of four primary alkaloids (arecoline, arecaidine, guvacine, and guvacoline) isolated from areca nut on zebrafish. We found that four alkaloids induced hyperactivity-like behaviors in zebrafish larvae. Cooperating the results with the previous study, molecular docking scores suggested these alkaloids might bind to multiple muscarinic acetylcholine receptors (mAChRs), and various best binding modes were shown. According to the adult zebrafish behavioral test, arecoline was found to slightly increase the locomotor activity and caused tightening shoaling formations of adult zebrafish. Meanwhile, zebrafish exposed to arecaidine have reduced aggressiveness and conspecific social interaction. Similar to arecaidine, guvacoline treatment also caused abnormalities in zebrafish social behaviors. Furthermore, the fish displayed abnormal exploratory behaviors after being exposed to guvacoline. Interestingly, altered fear response behaviors were only displayed by guvacine-treated fish besides their lower locomotor activity. Based on the results of molecular docking, we hypothesize that the behavior alterations might be a consequence of the interaction between alkaloids and multiple mAChRs in the nervous system. In summary, our study found that each alkaloid specifically affects adult zebrafish behaviors.

The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.

Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional cytosolic membrane trafficking protein with distinct roles in maintaining cellular homeostasis. Recent clinical reports have described 28 individuals possessing a de novo PACS-2 E209K mutation that present with epileptic seizures and cerebellar dysgenesis. As the PACS-2 E209K missense mutation has become a marker for neurodevelopmental disorders, we sought to characterize its biochemical properties. Accordingly, we observed that the PACS-2 E209K protein exhibited a slower turnover rate relative to PACS-2 wild type (WT) upon cycloheximide treatment in 293T cells. The longer half-life of PACS-2 E209K suggests a disruption in its proteostasis, with the potential for altered protein-protein interactions. Indeed, a regulatory protein in neurodevelopment known as 14-3-3ε was identified as having an increased association with PACS-2 E209K. Subsequently, when comparing the effect of PACS-2 WT and E209K expression on the staurosporine-induced apoptosis response, we found that PACS-2 E209K increased susceptibility to staurosporine-induced apoptosis in HCT 116 cells. Overall, our findings suggest PACS-2 E209K alters PACS-2 proteostasis and favors complex formation with 14-3-3ε, leading to increased cell death in the presence of environmental stressors.

An Unexpected Alteration Colonic Mucus Appearance in the Constipation Model via an Intestinal Microenvironment.

Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.

Methods for Collection of Extracellular Vesicles and Their Content RNA as Liquid Biopsy for Lung Cancer Detection: Application of Differential Centrifugation and Annexin A5 Coated Beads.

Extracellular vesicles (EVs) contain abundant extracellular RNA (exRNA), which can be a valuable source of liquid biopsy. However, as various RNA species exist in different types of EVs, lack of detailed characterization of these RNA species and efficient collection methods limits the clinical application of exRNA. In the present study, we measured two mRNAs, CK19 and PCTK1; one lncRNA, MALAT1; and two miRNAs, miR21 and miR155, in different EV fractions separated by differential centrifugation or captured by magnetic beads coated with annexin A5 (ANX beads). The results showed that in a cultured medium, the majority of mRNA and lncRNA exist in larger EVs, whereas miRNA exist in both large and small EVs from the differential centrifugation fractions. All these RNA species exist in ANX beads captured EVs. We then used ANX beads to capture EVs in plasma samples from non-small-cell lung cancer patients and age-matched healthy volunteers. We found that the ANX bead capturing could efficiently improve RNA detection from human plasma, compared with direct extraction of RNA from plasma. Using ANX-bead capturing and reverse transcription and quantitative PCR, we detected significantly higher levels of CK19 mRNA, MALAT1 lncRNA, and miR155 miRNA in the plasma of lung cancer patients. These facts suggested the collection methods strongly affect the results of exRNA measurement from EVs, and that ANX beads can be a useful tool for detecting exRNA from plasma samples in clinical application.

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux.

The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

Lanthanides Toxicity in Zebrafish Embryos Are Correlated to Their Atomic Number.

Rare earth elements (REEs) are critical metallic materials with a broad application in industry and biomedicine. The exponential increase in REEs utilization might elevate the toxicity to aquatic animals if they are released into the water due to uncareful handling. The specific objective of our study is to explore comprehensively the critical factor of a model Lanthanide complex electronic structures for the acute toxicity of REEs based on utilizing zebrafish as a model animal. Based on the 96 h LC50 test, we found that the majority of light REEs display lower LC50 values (4.19-25.17 ppm) than heavy REEs (10.30-41.83 ppm); indicating that they are atomic number dependent. Later, linear regression analyses further show that the average carbon charge on the aromatic ring (aromatic Cavg charge) can be the most significant electronic structural factor responsible for the Lanthanides' toxicity in zebrafish embryos. Our results confirm a very strong correlation of LC50 to Lanthanide's atomic numbers (r = 0.72), Milliken charge (r = 0.70), and aromatic Cavg charge (r = -0.85). This most significant correlation suggests a possible toxicity mechanism that the Lanthanide cation's capability to stably bind to the aromatic ring on the residue of targeted proteins via a covalent chelating bond. Instead, the increasing ionic bond character can reduce REEs' toxicity. In addition, Lanthanide toxicity was also evaluated by observing the disruption of photo motor response (PMR) activity in zebrafish embryos. Our study provides the first in vivo evidence to demonstrate the correlation between an atomic number of Lanthanide ions and the Lanthanide toxicity to zebrafish embryos.

Peroxisome Proliferator-Activated Receptor-α: A Pivotal Regulator of the Gastrointestinal Tract.

Peroxisome proliferator-activated receptor (PPAR)-α is a ligand-activated transcription factor distributed in various tissues and cells. It regulates lipid metabolism and plays vital roles in the pathology of the cardiovascular system. However, its roles in the gastrointestinal tract (GIT) are relatively less known. In this review, after summarizing the expression profile of PPAR-α in the GIT, we analyzed its functions in the GIT, including physiological control of the lipid metabolism and pathologic mediation in the progress of inflammation. The mechanism of this regulation could be achieved <i>via</i> interactions with gut microbes and further impact the maintenance of body circadian rhythms and the secretion of nitric oxide. These are also targets of PPAR-α and are well-described in this review. In addition, we also highlighted the potential use of PPAR-α in treating GIT diseases and the inadequacy of clinical trials in this field.

PACS-1 contains distinct motifs for nuclear-cytoplasmic transport and interacts with the RNA-binding protein PTBP1 in the nucleus and cytosol.

Phosphofurin acidic cluster sorting protein 1 (PACS-1) is canonically a cytosolic trafficking protein, yet recent reports have described nuclear roles for PACS-1. Herein, we sought to define the nuclear transport mechanism of PACS-1. We demonstrate that PACS-1 nucleocytoplasmic trafficking is dependent on its interaction with the nuclear transport receptors importin alpha 5 and exportin 1. PACS-1 nuclear entry and exit are defined by a nuclear localization signal (NLS, residues 311-318) and nuclear export signal (NES3, residues 366-375). Mutation of the PACS-1 NLS and NES3 altered the localization of a complex formed between PACS-1 and an RNA-binding protein, polypyrimidine tract-binding protein 1. Overall, we identify the nuclear localization mechanism of PACS-1 and highlight a potential role for PACS-1 in RNA-binding protein trafficking.

Combination of AgNPs and Domiphen is Antimicrobial Against Biofilms of Common Pathogens.

PURPOSE: The aim was to evaluate the antimicrobial potential of AgNPs synthesized with Artemisia argyi leaf extract and investigate the antimicrobial synergistic effects of AgNPs combined with domiphen and provide an efficient and broad-spectrum combination drug strategy. METHODS: AgNPs synthesized with Artemisia argyi leaf extract were studied using UV-vis spectroscopy, FTIR spectroscopy and particle size analysis. Then, Artemisia argyi leaf extract-synthesized AgNPs and domiphen were tested against Acinetobacter baumannii (ATCC 19606), Staphylococcus aureus (ATCC 6538), Escherichia coli (8099) and Candida albicans (ATCC 10231), respectively. Then, we explore synergistic antimicrobial effect and synergistic anti-biofilm effect through combined drug susceptibility test and combined drug minimum biofilm eradication concentration (MBEC50) test. RESULTS: Characteristic absorption bands of AgNPs were found near 430 nm in the UV-vis spectrum. Particle size analysis results revealed that the average particle size of Artemisia argyi leaf extract-synthesized AgNPs was 77.6 nm. Artemisia argyi leaf extract-synthesized AgNPs showed high antimicrobial activity against the above four strains. Minimum inhibitory concentration (MIC) of Artemisia argyi leaf extract-synthesized AgNPs against strains was 1 µg/mL for Acinetobacter baumannii, 2 µg/mL for Staphylococcus aureus, Escherichia coli and Candida albicans. MBEC50 of Artemisia argyi leaf extract-synthesized AgNPs against strains was 2 µg/mL for Acinetobacter baumannii, 4 µg/mL for Staphylococcus aureus, 1/2 µg/mL for Escherichia coli and 2 µg/mL for Candida albicans. The combination of Artemisia argyi leaf extract-synthesized AgNPs and domiphen has synergistic antimicrobial effect and synergistic anti-biofilm effect. Fractional inhibitory concentration (FIC) was ≤0.5. CONCLUSION: Artemisia argyi leaf extract-synthesized AgNPs had antimicrobial activity against the above four strains. The combination of Artemisia argyi leaf extract-synthesized AgNPs and domiphen has synergistic antimicrobial effects to reduce the dosage of each antimicrobial drugs. Artemisia argyi leaf extract-synthesized AgNPs and domiphen have synergistic anti-biofilm effects.

GLP-1 and Underlying Beneficial Actions in Alzheimer's Disease, Hypertension, and NASH.

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

Functions of Dendritic Cells and Its Association with Intestinal Diseases.

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

Downregulation of hsa_circ_0007534 restricts the proliferation and invasion of cervical cancer through regulating miR-498/BMI-1 signaling.

AIMS: Hsa_circ_0007534 has been reported to be a novel cancer-related circRNA affecting multiple cancers. However, little is known about the role of hsa_circ_0007534 in cervical cancer specifically. In the current study, we aimed to explore the expression and function of hsa_circ_0007534 in cervical cancer. MAIN METHODS: The expression of circRNA, miRNA and mRNA was measured using real-time quantitative polymerase chain reactions. Protein expression was assessed by Western blot. Knockdown of has_circ_0007534 was achieved by siRNA-mediated gene silencing. Cell proliferation was determined using a cell counting kit-8 and colony formation assays. Cell invasion was assessed using a Transwell invasion assay. RNA interactions were measured using an RNA pull-down and dual-luciferase reporter assays. KEY FINDINGS: The expression of hsa_circ_0007534 was upregulated in cervical cancer tissues and cell lines. Depletion of hsa_circ_0007534 decreased both the proliferation and invasion of cervical cancer cells. MicroRNA-498 (miR-498) was identified as a target of the miRNA encoded by hsa_circ_0007534. Levels of miR-498 were decreased in cervical cancer tissues, a finding that was inversely correlated with hsa_circ_0007534 expression. miR-498 overexpression repressed the proliferation and invasion of cervical cancer cells. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) was verified as a target gene of miR-498. BMI-1 overexpression reversed the effects of hsa_circ_0007534 depletion or miR-498 overexpression on cervical cancer cell proliferation and invasion. SIGNIFICANCE: Our study demonstrates that downregulation of hsa_circ_0007534 represses the proliferation and invasion of cervical cancer through regulating the miR-498/BMI-1 axis, suggesting the hsa_circ_0007534/miR-498/BMI-1 axis as a potential therapeutic target to treat cervical cancer.

TPX2 promotes cell proliferation and migration via PLK1 in OC.

BACKGROUND: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated proteinrequired for mitosis and spindle assembly. It has been revealed that TPX2 is overexpressedin various human cancers and promotes cancer progression. METHODS: The expression of TPX2 was examined in ovarian cancer (OC) tissues and by Western blotting, quantitative real-time reverse transcription PCR (qRT-PCR) and immunohistochemistry. The effects of TPX2 on proliferation and migration of two OC cell lines SKOV3and RMG1 were analyzed using the methylthiazol tetrazolium (MTT) assay, flow cytometry and transwell assay. The mechanisms underlying the effects of TPX2 on OC cells were explored by qRT-PCR and Western blot. RESULTS: In this study, we found that TPX2 was upregulated in OC tissues. We observed knockdown of TPX2 inhibited the expression of Polo-like kinase 1 (PLK1), which has an important role in the regulation of M phase of the cell cycle, and the activity of Cdc2, induced cell arrested at the G2/M phase and decreased proliferation. Moreover, our data revealed that the levels of PLK1, ß-catenin, MMP7 and MMP9 were inhibited following TPX2 knockdown, leading to decrease of cell migration. Finally, we showed that the restoration of PLK1 expression attenuated the anti-proliferation and anti-migration effects of TPX2 knockdown in OC cells. CONCLUSIONS: TPX2 promotes the proliferation and migration of human OC cells by regulating PLK1 expression.

Anxiety, happiness and self-esteem of western Chinese left-behind children.

China's unprecedented economic boom has led a massive number of children left-behind by their peasant parents who have immigrated to urban areas in search of work. In current study, we explored how being left behind is associated with children's positive emotions and negative psychological traits by examining the differences in levels of happiness, self-esteem and anxiety between left-behind children (LBC) and non-LBC. A total of 448 students (aged 7-16) from three schools in Sichuan Province in China responded to the questionnaire. Fourteen teachers of LBC were invited to one-to-one interviews for in depth responses to LBC's behaviors and psychological well-being. The results revealed that non-LBC showed a higher level of happiness (t=-0.21, df=258, p<0.01) and a lower level of anxiety (t=1.41, df=406, p<0.05) than LBC children. Among LBC, low grade children (primary school grades 3 and 4) reported a lower level of happiness (t=-0.73, df=216, p<0.01) and self-esteem (t=-0.24, df=191, p<0.01) than their older counterparts (primary school grades 5 and 6). The teachers' accounts confirmed the statistical results that LBC suffered from the deprivation of parental care. According to the teachers, as LBC grew older, they developed an understanding of their own circumstances and came to appreciate their parents' decisions. With appropriate and adequate support provided to both LBC and the caretakers around them such as relatives and teachers, it may be possible to reduce the adverse impacts of parental deprivation on LBC.

Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.

OBJECTIVE: Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. METHODS: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. RESULTS: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. CONCLUSIONS: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.

Cervical epithelial brightness by optical coherence tomography can determine histological grades of cervical neoplasia.

OBJECTIVE: The study aimed to determine if the difference in cervical epithelium brightness, as measured by optical coherence tomography (OCT), has potential as a distinguishing characteristic of normal, low-grade, high-grade (cervical intraepithelial neoplasia 2+), and cancer histological findings. MATERIALS AND METHODS: Information from 476 women was available for analysis. Demographic information was collected through in-person interview. All participants were human papillomavirus positive and/or had abnormal cytological finding and underwent colposcopy or unaided visual inspection and examination by OCT by quadrant. All women had a minimum of 4 OCT-matched cervical biopsies and endocervical curettage. Two sample t tests were used to measure differences in OCT image brightness by histological grades. RESULTS: Mean OCT image brightness differed significantly between each preinvasive histological grade and invasive cancer (p < .01 for all comparisons). Brightness as measured by OCT was also able to differentiate between squamous metaplasia and cervical intraepithelial neoplasia 3/cancer; p values were .004 and .003, respectively. CONCLUSIONS: Epithelial brightness is an important component of cervical epithelium diagnosis by OCT, and we plan to add it to our diagnostic mathematical algorithm in all future versions of OCT software.