Association between Salivary Hormones, Dental Caries, and Cariogenic Microorganisms during Pregnancy.

Objective: This study aimed to identify the salivary levels of six hormones (progesterone, estradiol, testosterone, cortisol, thyroxine T3, and triiodothyronine T4) in pregnant women, and to assess the association between salivary hormones, dental caries, and cariogenic microorganisms. Methods: This cross-sectional study included 181 low-income US pregnant women who were in their third trimester. Demographic details, oral hygiene practices, and medical backgrounds were obtained via questionnaires and medical records. Calibrated dentists obtained data on plaque index and caries status through comprehensive oral examinations. Unstimulated saliva was collected 2 h before eating and brushing. Salivary hormones were measured with a multiplex assay. Oral Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) were quantified via colony-forming unit (CFU) counts. A latent model was used to generate clusters of pregnant women based on salivary hormone levels, followed by post-clustering analysis. Factors associated with salivary cariogenic microorganisms were further evaluated via multiple regression analyses. Results: Estradiol, progesterone, testosterone, cortisol, T3, and T4 in saliva were detectable at rates of 92%, 97%, 77%, 99%, 71%, and 50%, respectively. Three distinct participant clusters (high, intermediate, and low) were identified based on salivary hormone levels. Intermediate-level and high-level clusters had increased numbers of decayed teeth, decayed surfaces, ICDAS scores, and salivary S. mutans and C. albicans, compared to the low-level cluster (p < 0.05). Covariate analysis demonstrated that the high-level cluster was positively associated with salivary carriage of S. mutans (CFU/mL) (p < 0.05). Participants with higher levels of progesterone, estradiol, testosterone, and cortisol were associated with a high carriage status of S. mutans in saliva (>105 CFU/mL) (p < 0.05). Conclusions: This study demonstrated the feasibility of detecting salivary hormones during pregnancy and revealed the positive association between salivary steroid hormones and cariogenic pathogens.

Deciphering two decades of cellular reprogramming in cancer: A bibliometric analysis of evolving trends and research frontiers.

Recent research has reevaluated the traditional view of cancer's linear progression and recurrence by introducing cellular reprogramming a process in which cancer cells can their state under certain conditions. This change is driven by a combination of genetic and epigenetic factors, with pivotal roles played by key genes, and pathways, notably Wnt and Notch. The complexity of cancer's behavior is further influenced by factors such as the epithelial-mesenchymal transition (EMT) and therapy-induced stress, both of which are significant contributors to cancer recurrence. In this context bibliometric analysis emerges as a crucial tool for evaluating the impacts and trends within scientific literature. Our study utilized bibliometrics to analysis the role of cellular reprogramming oncology over the past two decades, highlighting its potential to improve cancer treatment outcomes. In conducting this analysis, we searched for literature search on cellular reprogramming (CR) in the Web of Science database, covering the years 2002-2022. We employed visualization tools like Citespace, VOSviewer, and Bibliometrix to analyze the collected data resulting in a dataset of 3102 articles. The United States and China emerged as leading contributors to this field, with the University of Texas MD Anderson Cancer Center being the most prolific institution. Menendez was the most influential scholar in this research domain. Cancers was the journal with the most publications on this subject. The most local-cited document was the article titled "Hallmarks of Cancer: The Next Generation". A comprehensive analysis has been conducted based on keywords and cited references. In recent years, the research emphasis has shifted to "extracellular vesicles," "cancer therapy," and "cellular plasticity". Therefore, this analysis uses bibliometrics to chart cutting-edge progress in cancer's cellular reprogramming, aiding experts to quickly understand and innovate in this crucial area.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Current status and implementation strategies of patient education in core outcome set development.

OBJECTIVE: Patient participation is essential for Core Outcome Set (COS) development studies. Patient education during participation may help patients better express their views in COS studies. This study aimed to investigate the current status of patient participation and the specified educational information in COS studies. METHODS: We conducted a systematic review of COS development studies. Information on patient participation in COS research, and especially details of patient education, was analyzed. RESULTS: In total, 146 COS development studies were included in this review. Of these, 125 studies (85.6%) mentioned patient participation. Most studies did not provide explicit information on patient participation. Some studies mentioned recruiting patients, but ultimately, none of them responded. Six studies reported conducting patient education through workshops, creating patient forums, or providing videos and slides. However, these studies did not provide details on education. Twenty-three studies used the plain language to explain patient outcomes. CONCLUSION: COS developers are increasingly focusing on patient participation. However, only a few COS studies have explicitly reported conducting measures related to patient education. Further patient education is necessary when they participate in the development of a new Core Outcome Set. PRACTICE IMPLICATION: This article provides implementation strategies related to patient education for future COS development studies.

PTBP1 as a potential regulator of disease.

Polypyrimidine tract-binding protein 1 (PTBP1) is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which plays a key role in alternative splicing of precursor mRNA and RNA metabolism. PTBP1 is universally expressed in various tissues and binds to multiple downstream transcripts to interfere with physiological and pathological processes such as the tumor growth, body metabolism, cardiovascular homeostasis, and central nervous system damage, showing great prospects in many fields. The function of PTBP1 involves the regulation and interaction of various upstream molecules, including circular RNAs (circRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These regulatory systems are inseparable from the development and treatment of diseases. Here, we review the latest knowledge regarding the structure and molecular functions of PTBP1 and summarize its functions and mechanisms of PTBP1 in various diseases, including controversial studies. Furthermore, we recommend future studies on PTBP1 and discuss the prospects of targeting PTBP1 in new clinical therapeutic approaches.

Tumor cell-induced platelet aggregation accelerates hematogenous metastasis of malignant melanoma by triggering macrophage recruitment.

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis. METHODS: We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME. RESULTS: We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1ß. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. CONCLUSIONS: TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.

Synthesis of functional polyacrylamide (co)polymers by organocatalyzed post-polymerization modification of non-activated esters.

The broad application of polyacrylamides (PAMs) has greatly promoted the development of new synthetic methods to prepare PAM-based functional (co)polymers regarding their traditional preparation via the direct polymerization of various acrylamide monomers. Herein, we have explored the post-polymerization modification of the poly(2,2,2-trifluoroethyl acrylate) (PTFEA) homopolymer, a typical non-activated ester, and various amines using the organo-catalytic system involving 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,2,4-triazole (TA). The reaction kinetics (e.g., the optimized reaction solvent, temperature, time, initial molar ratio of amines to esters and the molar ratio of DBU to TA) were carefully studied with the modulus substrate of iso-propylamine as the formed poly(iso-propyl acrylamide) (PNIPAM) representing the most investigated PAM. The full and partial amidation of the esters in PTFEA could be precisely regulated just by controlling the kinetic conditions to give (co)polymers with designable compositions and structures. We have demonstrated that the poly(N-acryloyl pyrrolidine) obtained by the post-polymerization modification of non-activated ester and pyrrolidine exhibited a noticeable phase transition, which confirmed the robustness and versatility of the post-polymerization modification. The described method paves the way for the synthesis of various (co)polymers with amide side chains from readily available polymer precursors.

Cycloisomerization of Alkyne-Tethered N-Acyloxycarbamates to 2-(3H)Oxazolones through Nitrenoid-Mediated Carboxyamidation.

The cycloisomerization of alkyne-tethered N-benzoyloxycarbamates to 2-(3H)oxazolones is described. Two catalytic systems are tailored for intramolecular 5-exo-alkyne carboxyamidation and concomitant alkene isomerization. PtCl2 /CO (5 mol%, toluene, 100 °C) promotes both carboxyamidation and alkene isomerization but has a limited substrate scope. On the other hand, FeCl3 (5 mol%, CH3 CN, 100 °C) promotes carboxyamidation effectively but a cocatalyst is required for the exocyclic alkene isomerization. Thus, a two-step one-pot protocol has been developed for a broader reaction scope, which involves FeCl3 -catalyzed carboxyamidation and base-induced alkene isomerization. Crossover experiments suggest that these reactions proceed mainly through a mechanism involving acylnitrenoid intermediates rather than carbenoid intermediates.

Inhibitory effects of polyphenols from black chokeberry on advanced glycation end-products (AGEs) formation.

Plant-based polyphenols are known to exert mitigating effects on the harmful consequences of advanced glycation. In this study, the antioxidant and antiglycation properties of purified black chokeberry polyphenol and its dominant monomers were studied. The phenolics of black chokeberry had a significant inhibitory effect on glycation products at all stages. The highest inhibition of fructosamine (72.27%) was achieved by chlorogenic acid (CA). Epigallocatechin gallate (EGCG) showed an 84.47% inhibition of α-dicarbonyl and 54.44% inhibition of AGEs (advanced glycation end-products). However, the inhibition of α-dicarbonyl was impacted by the presence of Cu2+. In addition, an EGCG-induced increase in the protein α-helical structure to 21.43% was observed. Overall, EGCG was the main component inhibited protein glycosylation in the simulated glycation system. Furthermore, the mechanism of inhibition was a combination of scavenging free radicals, capturing metal ions, and alleviating changes in the secondary structure of proteins.

Study on the preparation conditions and degradation performance of an efficient immobilized microbial agent for marine oil pollution.

In the process of handling marine oil spills accidents, the biological method has attracted wide attention due to its low cost and no secondary pollution. However, in the process of practical application, there are problems such as low microbial density and great influence of environmental factors when the oil is treated by spraying microorganisms on the sea surface. This study used immobilized microorganism technology to solve the above-mentioned problems. In this study, the bacteria immobilized on cinnamon shell (CS) with good degradation performance were obtained by optimizing preparation conditions. Under the optimal conditions of sodium alginate (SA) concentration of 4.57%, CS concentration of 1.28%, and the CaCl2 concentration of 2.45%, the degradation rate of diesel in 5 days reached 74.04%. The reusability of immobilized microbial agents was further studied. The study designed three cycles of repeated degradation experiments. The results showed that the degradation rate of diesel can still reach 60.12% after three times of reuse, which indicated the reusability of the immobilized microbial agents was excellent. The decrease in degradation rate of diesel was mainly related to the fragmentation of immobilized microbial agents and the decrease in microbial biomass.

Hyperbranched Polyglycerols as Robust Up-Conversion Nanoparticle Coating Layer for Feasible Cell Imaging.

Owing to the wide spectrum of excitation wavelengths of up-conversion nanoparticles (UCNPs) by precisely regulating the percentage of doping elements, UCNPs have been emerging as bioimaging agents. The key drawback of UCNPs is their poor dispersibility in aqueous solution and it is hard to introduce the chemical versatility of function groups. In our study, we present a robust and feasible UCNP modification approach by introducing hyperbranched polyglycerols (hbPGs) as a coating layer. When grafted by hbPGs, the solubility and biocompatibility of UCNPs are significantly improved. Moreover, we also systematically investigated and optimized the chemical modification approach of amino acids or green fluorescence protein (GFP), respectively, grafting onto hbPGs and hbPGs-g-UCNP by oxidizing the vicinal diol to be an aldehyde group, which reacts more feasibly with amino-containing functional molecules. Then, we investigated the drug-encapsulating properties of hbPGs-Arg with DOX and cell imaging of GFP-grafted hbPGs-g-UCNP, respectively. The excellent cell imaging in tumor cells indicated that hbPG-modification of UCNPs displayed potential for applications in drug delivery and disease diagnosis.

Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin.

Novel molecular mechanisms of the pathophysiology of heart failure (HF) are continuously being discovered, including epigenetic regulation. Among epigenetic marks, the role of DNA hypomethylation in shaping heart morphology and function in vivo and the pathogenesis of cardiomyopathy and/or HF, especially in adults, has not been clearly established. Here we show that the strong expression of DNA methyltransferase 1 (Dnmt1) is obviously downregulated in the WT adult rat heart with age. By contrast, the expression of Dnmt1 is upregulated suddenly in heart tissues from pressure overload-induced HF mice and adriamycin-induced cardiac injury and HF mice, consistent with the increased expression of Dnmt1 observed in familial hypertrophic cardiomyopathy (FHCM) patients. To further assess the role of Dnmt1, we generated myocardium-specific Dnmt1 knockout (Dnmt1 KO) rats using CRISPR-Cas9 technology. Echocardiographic and histopathological examinations demonstrated that Dnmt1 deficiency is associated with resistance to cardiac pathological changes and protection at the global and organization levels in response to pathological stress. Furthermore, Dnmt1 deficiency in the myocardium restricts the expressional reprogramming of genes and activates pathways involved in myocardial protection and anti-apoptosis in response to pathological stress. Transcriptome and genome-wide DNA methylation analyses revealed that these changes in regulation are linked to alterations in the methylation status of genes due to Dnmt1 knockout. The present study is the first to investigate in vivo the impact of genome-wide cardiac DNA methyltransferase deficiency on physiological development and the pathological processes of heart tissues in response to stress. The exploration of the role of epigenetics in the development, modification, and prevention of cardiomyopathy and HF is in a very preliminary stage but has an infinite future.

Systematic degradation mechanism and pathways analysis of the immobilized bacteria: Permeability and biodegradation, kinetic and molecular simulation.

In order to effectively improve the degradation rate of diesel, a systematic analysis of the degradation mechanism used by immobilized bacteria is necessary. In the present study, diesel degradation mechanisms were assessed by analyzing permeability, biodegradation, adsorption kinetics, and molecular simulation. We found that bacteria immobilized on cinnamon shells and peanut shells degraded relatively high amounts of diesel (69.94% and 64.41%, respectively). The primary degradation pathways used by immobilized bacteria included surface adsorption, internal uptake, and biodegradation. Surface adsorption was dominant in the early stage of degradation, whereas biodegradation was dominant in later stages. The diesel adsorption rate of the immobilized bacteria was in agreement with the pseudo second-order kinetic model. The immobilized bacteria and diesel interacted through hydrogen bonds.

Human genes influence the interaction between Streptococcus mutans and host caries susceptibility: a genome-wide association study in children with primary dentition.

Streptococcus mutans is a well-known cause of dental caries, due to its acidogenicity, aciduricity, and ability to synthesize exopolysaccharides in dental plaques. Intriguingly, not all children who carry S. mutans manifest caries, even with similar characteristics in oral hygiene, diet, and other environmental factors. This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries; however, the association between host genetics, S. mutans, and dental caries remains unclear. Therefore, this study examined the influence of host gene-by-S. mutans interaction on dental caries. Genome-wide association analyses were conducted in 709 US children (<13 years old), using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS). A generalized estimating equation was used to examine the gene-by-S. mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries). Sequentially, the COHRA and GEIRS data were used to identify potential interactions and replicate the findings. Three loci at the genes interleukin 32 (IL32), galactokinase 2 (GALK2), and CUGBP, Elav-like family member 4 (CELF4) were linked to S. mutans carriage, and there was a severity of caries at a suggestive significance level among COHRA children (P < 9 × 10-5), and at a nominal significance level among GEIRS children (P = 0.047-0.001). The genetic risk score that combined the three loci also significantly interacted with S. mutans (P < 0.000 1). Functional analyses indicated that the identified genes are involved in the host immune response, galactose carbohydrate metabolism, and food-rewarding system, which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.

A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal Block for Sternotomy.

BACKGROUND: Optimal pain control continues to be a concern in cardiac surgery. Current strategies for postoperative pain management often yield suboptimal results. The superiority of Exparel (Pacira Pharmaceuticals, Inc, Parsippany, NJ) in providing postoperative pain control and opioid sparing is equivocal. This prospective, randomized, double-blind study examines the efficacy of Exparel as a novel single-dose application parasternal nerve block in postoperative pain control and opioid sparing. METHODS: This single-surgeon study included 79 patients undergoing median sternotomy for coronary revascularization. Study participants were randomized to either the drug or a control arm. Each participant received Exparel or normal saline placebo administered as a parasternal nerve block. Postoperative pain was rated according to the nonverbal pain scale or numeric rating scale. Total amount of narcotic pain medication used and patients' pain scores within the first 72 hours postoperatively were compared. Secondary outcomes compared the intensive care unit length of stay, hospital length of stay, time to extubation, time to return of bowel function, and time to return to work or daily activities. RESULTS: The primary endpoint of pain levels between the two groups demonstrated no significant difference when analyzing the individual time points postoperatively. However, overall pain levels were significantly lower in the study drug group (p = 0.04). There was no significant difference in the amount of analgesics required postoperatively or in secondary endpoints between the groups. CONCLUSIONS: Exparel does not provide an opioid-sparing benefit or any secondary outcome benefit compared with placebo. Exparel may be associated with a marginal decrease in postoperative pain levels. (Parasternal Nerve Bock in Cardiac Patients; NCT01826851.).

Obesity candidate genes, gestational weight gain, and body weight changes in pregnant women.

OBJECTIVE: To examine the associations of two obesity-associated genes, FTO (rs9939609) and GNB3 (rs5443) single nucleotide polymorphisms (SNPs), with early pregnancy body mass index, gestational weight gain, and postpartum weight retention. METHODS: Secondary data analysis of self-identified white (n = 580) and black (n = 194) women who participated in a randomized controlled trial (2009-2014) and provided a saliva sample of DNA. Bivariate relationships were assessed using analysis of variance. Multiple regression models assessed the relationship between outcomes and gene SNPs, controlling for income, parity, and smoking status. RESULTS: FTO and GNB3 gene associations with pregnancy weight were different by racial group and early pregnancy body mass index. Obese black women homozygote for the FTO risk allele (AA) had a higher gestational weight gain compared with non-risk homozygotes (TT) (P = 0.006). GNB3 non-risk CC homozygotes tended to have a lower gestational weight gain compared with heterozygotes (P = 0.05). White GNB3 C carriers tended to be heavier in early pregnancy (P <0.1) and GNB3 homozygote (TT) overweight women tended to have lower postpartum weight retention than C carriers. CONCLUSIONS: The FTO gene and possibly the GNB3 gene are associated with high gestational weight gain in obese black women. Obese carriers of the FTO risk allele gained 4.1 kg (AT) and 7.6 kg (TT) more than those without risk alleles. Overweight GNB3 heterozygotes (CT) gained 6.6 kg less than homozygotes (CC). Overweight or obese black women who have either risk variant are at risk for high gestational weight gain.

Optical coherence tomography and computer-aided diagnosis of a murine model of chronic kidney disease.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function over time. Histopathological analysis of the condition of glomeruli and the proximal convolutional tubules over time can provide valuable insights into the progression of CKD. Optical coherence tomography (OCT) is a technology that can analyze the microscopic structures of a kidney in a nondestructive manner. Recently, we have shown that OCT can provide real-time imaging of kidney microstructures in vivo without administering exogenous contrast agents. A murine model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by OCT. OCT images of the rat kidneys have been captured every week up to eight weeks. Tubular diameter and hypertrophic tubule population of the kidneys at multiple time points after ADR injection have been evaluated through a fully automated computer-vision system. Results revealed that mean tubular diameter and hypertrophic tubule population increase with time in post-ADR injection period. The results suggest that OCT images of the kidney contain abundant information about kidney histopathology. Fully automated computer-aided diagnosis based on OCT has the potential for clinical evaluation of CKD conditions.

High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5.

BACKGROUND: Claudins are a family of integral membrane proteins and are components of tight junctions (TJs). Many TJ proteins are known to tighten the cell structure and maintain a barrier. Claudin-2 forms gated paracellular channels and allows sodium ions and other small positively charged ions to cross between adjacent cells. Recently, we found that vitamin D receptor (VDR) enhanced Claudin-2 expression in colon and that bile salt receptors VDR and Takeda G-protein coupled receptor5 (TGR5) were highly expressed in esophageal adenocarcinoma (EAC) and precancerous lesions. Here, we examined the expression of Claudin-2 in EAC and precancerous lesions and its association with VDR and TGR5 expression. METHODS: Claudin-2 expression was examined by immunohistochemistry on tissue microarrays, containing EAC, high grade dysplasia (HGD), low grade dysplasia (LGD), Barrett's esophagus (BE), columnar cell metaplasia (CM), squamous cell carcinoma (SCC), and squamous epithelium (SE) cases. Intensity (0 to 3) and percentage were scored for each case. High expression was defined as 2-3 intensity in ≥ 10% of cells. RESULTS: Claudin-2 was highly expressed in 77% EAC (86/111), 38% HGD (5/13), 61% LGD (17/28), 46% BE (18/39), 45% CM (29/65), 88% SCC (23/26), and 14% SE (11/76). It was significantly more highly-expressed in EAC, SCC and glandular lesions than in SE and more in EAC than in BE and CM. A significant association was found between Claudin-2 expression and VDR and TGR5 expression. No significant association was found between expression of Claudin-2 and age, gender, grade, stage, or patients' survival time in EAC and SCC. CONCLUSIONS: We conclude that Claudin-2 expression is significantly associated with bile acid receptors VDR and TGR5 expression. Our studies identify a novel role of a tight junction protein in the development and progression of esophageal mucosal metaplasia, dysplasia and carcinoma.

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography.

Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is difficult to detect the subsurface lesions. In this research, we investigated the feasibility of a novel multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. The C57BL/6J-ApcMin/J mice were imaged using OCT and FLOT, and the correlated histopathological diagnosis was obtained. Quantitative structural (scattering coefficient) and molecular (relative enzyme activity) parameters were obtained from OCT and FLOT images for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 88.23% (82.35%) for sensitivity (specificity) compared to either modality alone. This study suggested that combining OCT and FLOT is promising for subsurface cancer detection, diagnosis, and characterization.

MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions.

Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and precancerous lesions. The mean percentage of MCM4, MCM7, and Ki-67 expression increased from squamous epithelium (5.5%, 7.3%, and 5.9%, respectively), to columnar cell metaplasia (11.2, 13.5%, and 3.4%), Barrett's esophagus (27.7%, 35.3%, and 8.3%), low-grade dysplasia (42.6%, 52.2%, and 12.9%), high-grade dysplasia (63.2%, 77.7%, and 29.6%), adenocarcinoma (61.3%, 75.5%, and 24.5%), and squamous cell carcinoma (74.1, 85.4%, and 36.3%). The percentages of MCM4 and MCM7 expression were significantly higher than Ki-67 expression. Using univariate analysis we found a high percentage of MCM4 expression (>70%) to be significantly associated with lymph node metastasis and shorter survival in the adenocarcinoma group. We also demonstrated the percentage of MCM4 and MCM7 expression to be significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma and precancerous lesions. MCM4 and MCM7 may serve as more sensitive proliferative markers for the evaluation of esophageal lesions.