Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis. Gemcitabine remains an effective option for the majority of PDAC patients. Unfortunately, currently no ...reliable prognostic and predictive biomarkers of therapeutic response are available for the patients with PDAC. Laminin γ2 (LAMC2) is overexpressed in several cancers, and its high expression facilitates cancer development and chemoresistance. However, its functional role in PDAC remains unclear, and a better understanding of this will likely help improve the prognosis of PDAC patients. This study aimed to elucidate the clinical and biological role of LAMC2 in PDAC. We first analyzed the expression levels of LAMC2 by real-time reverse transcription PCR in a cohort of 114 PDAC patients. Interestingly, higher expression of LAMC2 significantly correlated with poor survival in PDAC cohort. In addition, elevated LAMC2 expression served as a potential prognostic marker for survival. Subsequently, functional characterization for the role of LAMC2 in PDAC was performed by small interfering RNA knockdown in pancreatic cancer (PC) cell lines. Interestingly, inhibition of LAMC2 in PC cells enhanced the gemcitabine sensitivity and induction of apoptosis. Moreover, it inhibited colony formation ability, migration and invasion potential. Furthermore, LAMC2 regulated the expression of epithelial–mesenchymal transition (EMT) phenotype. In addition, LAMC2 significantly correlated with genes associated with the expression of ATP-binding cassette (ABC) transporters in PC cells and PDAC patients. In conclusion, these results suggest that LAMC2 regulates gemcitabine sensitivity through EMT and ABC transporters in PDAC and may be a novel therapeutic target in PDAC patients.
LAMC2 plays a significant role in pancreatic cancer cells through regulation of EMT and ABC transporters associated with cellular migration and invasion, resulting in poor prognosis and gemcitabine sensitivity in patients with pancreatic cancer.
Compared with other organisms, plants have an extraordinary capacity for self-repair. Even if the entire tissues, including the stem cells, are resected, most plant species are able to completely ...regenerate whole tissues. However, the mechanism by which plants efficiently regenerate the stem cell niche during tissue reorganization is still largely unknown. Here, we found that the signaling mediated by plant steroid hormones brassinosteroids is activated during stem cell formation after root tip excision in Arabidopsis. Treatment with brassinazole, an inhibitor of brassinosteroid biosynthesis, delayed the recovery of stem cell niche after root tip excision. Regeneration of root tip after resection was also delayed in a brassinosteroid receptor mutant. Therefore, we propose that brassinosteroids participate in efficient root tip regeneration, thereby enabling efficient tissue regeneration to ensure continuous root growth after resection.
Developmental and environmental signals converge on cell cycle machinery to achieve proper and flexible organogenesis under changing environments. Studies on the plant cell cycle began 30 years ago, ...and accumulated research has revealed many links between internal and external factors and the cell cycle. In this review, we focus on how phytohormones and environmental signals regulate the cell cycle to enable plants to cope with a fluctuating environment. After introducing key cell cycle regulators, we first discuss how phytohormones and their synergy are important for regulating cell cycle progression and how environmental factors positively and negatively affect cell division. We then focus on the well-studied example of stress-induced G2 arrest and view the current model from an evolutionary perspective. Finally, we discuss the mechanisms controlling the transition from the mitotic cycle to the endocycle, which greatly contributes to cell enlargement and resultant organ growth in plants.
•Periodontitis is initiated by oral bacterial dysbiosis-induced inflammation.•Tissue destruction is mainly caused by overactive inflammation & oxidative stress.•Host modulation therapy (HMT) ...strategies are aimed to support periodontal therapy.•HMT agents have substantial positive effects in maintaining homeostasis.•Modulating the immune response & oxidative stress may improve periodontal homeostasis.
To highlight the shifting paradigm of periodontitis, describe mechanism of periodontal bone destruction, and propose an updated host modulation therapy (HMT) strategy. To add further clinical relevance, related studies investigating the efficacy of several HMT agents in periodontitis will be discussed.
Literature searches were conducted from articles published in PubMed using keywords “periodontal disease AND periodontitis AND host modulation therapy AND anti-inflammatory AND antioxidant”, and then the findings were comprehensively summarized and elaborated.
Accumulating evidence indicates that periodontitis is no longer defined solely as a pathogen-induced disease; rather, it is now recognized as a consequence of uncontrolled immune response and oxidative stress leading to periodontal tissue damage. Although periodontopathic bacteria initiate the disease, inflammation and oxidative stress were reported to be the main causes for the severity of tissue destruction. Thus, since the concept of periodontitis has shifted, our approach to its management needs to be adjusted to accommodate the latest paradigm. Nowadays, the modulation of inflammation and oxidative stress is considered a target of HMT. HMT agents, such as probiotics, anti-inflammatory drugs, anti-chemokines, lipid mediators, and bio-active fatty acids, have been extensively investigated for their remarkable functions in modulating the immune response and providing antioxidant effects.
Findings from in vitro, in vivo, and human studies frequently demonstrate positive association by the administration of HMT in periodontitis. HMT strategy targeted on anti-inflammatory and antioxidant in periodontitis might serve as an excellent therapeutic approach to reach the level of clinical benefit.
Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have ...previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Porhyromonas gingivalis, a causative bacterium of periodontitis, is implicated in the etiology of rheumatoid arthritis (RA), mainly because of expressing peptidyl arginine deiminase (PAD) that ...generates RA-related autoantigens. However, compared with other periodontopathic bacteria, the precise role of P. gingivalis in RA is largely unknown. We found that orally administered P. gingivalis changed the gut microbiome with concomitant elevation of serum endotoxin and inflammatory markers, and impairment of the gut barrier function. Based on findings showing a relationship between gut microbiota and RA, we investigated whether the change of gut microbiota induced by P. gingivalis and Prevotella intermedia, another periodontopathic bacterium without PAD, is associated with collagen-induced arthritis (CIA). DBA/1J mice were orally administered with or without bacteria followed by induction of CIA. P. gingivalis, but not P. intermedia, administration significantly aggravated arthritis with increased interleukin-17 levels in sera and culture supernatants, increased Th17 cell proportions among mesenteric lymphocytes, and a significant change in the gut microbiome. However, P. gingivalis administration did not elevate the level of anti-citrullinated protein antibody. These results suggest a unique role of P. gingivalis in the link between periodontitis and RA by affecting the gut immune system and the gut microbiota composition.
In this study, we propose a method that can be used to enhance the configuration of mobile robots equipped with articulated legs and wheels by simultaneously optimizing leg joint angles and wheel ...positions using model predictive control (MPC). To present a manageable expression for MPC, the kinematics of a robot that has highly articulated legs with wheels at their ends are represented as serially connected constrained links. The other end of the leg is constrained by its position relative to the robot body. To actively allocate and adapt movements to the surrounding environment, we use a potential field method applied to each wheel. Our method is based on the following strategy. First, we will design a simple collision-free reference path for a point mass, and then we will apply MPC to induce optimal path tracking control that balances the input and artificial potential costs. This will allow the robot to adapt its wheel position configurations to the surrounding environment. Based on that strategy, we conducted numerical simulations and experiments using an actual mobile robot to verify the efficacy and feasibility of our proposed method, the results of which demonstrated its effective ability to adaptively configure its articulated legs in ways that allowed the robot to avoid obstacles.
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•Active leg configuration during obstacle avoidance is proposed.•Enhanced leg configuration is achieved using model predictive control.•Kinematics of articulated leg is represented as serially connected constraints.•Experiments is executed to demonstrate the efficacy of our proposed method.
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•Oxygen storage and release performances of Pt/CeO2-ZrO2 catalysts are analyzed.•This is done by flushing CO and O2 alternately in a periodic manner.•The oxygen storage and release ...processes are both visualized directly.•Effective OSCs are determined based on CO and O2 breakthrough influxes.•Catalysts on CZ oxides with homogeneous structure exhibit high effective OSCs.
To clarify the gap between the effective oxygen storage capacity (OSC) and complete OSC of Pt/CeO2-ZrO2 (CZ) catalysts, a quick-response reactor coupled with a high-time-resolution mass spectrometer was used to measure oxygen storage and release by flushing CO and O2 alternately and periodically. Hence, both oxygen storage and release were visualized together and the effective OSCs were determined based on the breakthrough influxes of CO and O2. The obtained effective OSCs varied with the CO concentration and were much lower than the complete OSC as determined by the conventional CO2 integration method. In accordance with the high oxygen mobility, as determined by the 18O/16O isotopic exchange reaction, the Pt catalysts supported on CZ oxides with a homogeneous and ordered Ce-Zr structure exhibited very high OSCs even at very low Pt loadings and low CO concentrations.
Objective
IgG4‐related disease (IgG4‐RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. ...This work was undertaken to develop and validate an international set of classification criteria for IgG4‐RD.
Methods
An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included.
Results
A 3‐step classification process was developed. First, it must be demonstrated that a potential IgG4‐RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4‐RD. Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4‐RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval 95% CI 97.2–99.8%) and a sensitivity of 85.5% (95% CI 81.9–88.5%). In the second, the specificity was 97.8% (95% CI 93.7–99.2%) and the sensitivity was 82.0% (95% CI 77.0–86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds.
Conclusion
ACR/EULAR classification criteria for IgG4‐RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.
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