Recently long non-coding RNAs (lncRNAs) have emerged as novel gene regulators involved in tumorigenic processes, including oral squamous cell carcinoma (OSCC). Here, we identified a ...differentiation-related lncRNA, terminal differentiation-induced non-coding RNA (TINCR). However, its biological function and clinicopathological significance in OSCC still remain unclear.
The lncRNA expression profiles in OSCC tissues and paired adjacent non-tumor tissues (NATs) from 10 patients were detected by lncRNA microarrays. Weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment were performed to identify the most significant module and module functional annotation, respectively. Potential differentiation-related lncRNAs were screened by differential expression analysis. TINCR was further confirmed in OSCC cell lines and tissues of another patient cohort by using qRT-PCR. The correlation between the TINCR expression level and clinicopathological characteristics was analyzed. The effects of TINCR on cell differentiation, migration and invasion were assessed by knockdown or knock-in
and
.
WGCNA and GO enrichment analysis showed that one co-expression network was significantly enriched for epithelial cell differentiation, among which, TINCR was significantly downregulated. qRT-PCR analyses validated down-regulation of TINCR in tumor tissues compared with paired NATs, and its expression was closely correlated with pathological differentiation and lymph node metastasis in patients with OSCC. Patients with lower TINCR expression levels had worse survival. Cell function experiments showed that TINCR played a crucial role in epithelial differentiation. Both TINCR and epithelial differentiation-associated genes, including IVL and KRT4, were significantly upregulated during OSCC cell calcium-induced differentiation but were reduced when cell dedifferentiation occurred in tumor spheres. Overexpression of TINCR dramatically suppressed cell dedifferentiation, migration and invasion
, while knockdown of TINCR had the opposite effects. Upregulation of TINCR significantly elevated the expression of terminal differentiation genes and repressed tumor growth
. Moreover, TINCR significantly suppressed the activation of JAK2/STAT3 signaling in OSCC cells.
Our study suggests that TINCR functions as a tumor suppressor by inducing cell differentiation through modulating JAK2/STAT3 signaling in OSCC. TINCR may serve as a prognostic biomarker and therapeutic target for OSCC.
This study had two purposes. The first purpose of the study was to compare the electromyographic(EMG) and dynamic characteristics in injured and non-injured legs during the one-legged heel-raise test ...after a unilateral Achilles repair. The second purpose was to determine the correlations between the EMG results and the dynamic characteristics and between the characteristics in the eccentric phase and jumping distance. Twenty-six participants who underwent an Achilles repair between 4 and 12 months prior to the measurement were recruited to perform the following bilateral tests: (1) one-legged heel-raise test with measurements of muscle activation, kinematics, and kinetics and (2) one-legged forward jumping. During the heel-raise exercise, there were increases of the EMG amplitudes in the soleus and tibialis anterior muscles, lower ankle joint angle and angular velocity, lower normalized ground reaction force, and mechanical work in the repaired legs in comparison to the non-injured legs. The EMG results of the medial gastrocnemius and soleus muscles correlated with the dynamic results (rs = 0.467 and −0.537). Furthermore, the dynamic data in the eccentric phase were correlated with the jumping performance (rs = 0.575 and −0.471). It is concluded the soleus muscle undergoes neuromechanical changes, including changes in EMG and dynamic characteristics, and changes affecting jumping performance.
Purpose
Older adults with hyperkyphosis might have a high risk of falls since their whole body center of mass may shift to the boundary of the base of support. Body composition changes, such as low ...bone mineral content (BMC), decreased muscle mass, high body mass index (BMI), and increased fat mass are common in older adults with hyperkyphosis. This study aimed to investigate the relationship between body composition and balance performance using a biomechanical analysis in older adults with hyperkyphosis.
Methods
Thirty older adults with hyperkyphosis were recruited. BMC, muscle mass, BMI, and fat mass were measured for body composition. Balance performances were determined with walking, quiet standing, and forward reach. Gait speed, step length, center of mass–center of pressure inclination angle of heel strike (Inc-HS) and toe off (Inc-TO) during walking, center of mass–center of pressure inclination angle during quiet standing (Inc-QS), and reaching distance were calculated.
Results
BMC had a moderately positive correlation with gait speed (r = 0.48,
p
< 0.01) and a moderately positive correlation with step length (r = 0.43,
p
= 0.01). Muscle mass had a moderately positive correlation with step length (r = 0.41,
p
= 0.02), moderately positive correlation with Inc-HS (r = 0.36,
p
= 0.04), and moderately positive correlation with reaching distance (r = 0.43,
p
= 0.01). No significant correlations were found among BMI, fat mass and balance performance.
Conclusion
BMC and muscle mass should be considered as factors that might affect walking and forward reach in older adults with hyperkyphosis.
Currently, patients with lumbar spinal stenosis (LSS) have two treatment options: nonoperative conservative treatment and surgical treatment. Because surgery is invasive, patients often prefer ...conservative treatment as their first choice to avoid risks from surgery. However, the effectiveness of nonoperative conservative treatment for patients with LSS may be lower than expected because of individual differences. Rules to determine whether patients with LSS should undergo surgical treatment merits exploration. In addition, without a decision-making system to assist patients undergoing conservative treatment to decide whether to undergo surgical treatment, medical professionals may encounter difficulty in providing the best treatment advice. This study collected medical record data and magnetic resonance imaging diagnostic data from patients with LSS, analyzed and consolidated the data through data mining techniques, identified crucial factors and rules affecting the final outcome the patients with LSS who opted for conservative treatment and ultimately underwent surgical treatment, and, finally, established an effective prediction model. This study applied logistic regression (LGR) and decision tree algorithms to extract the crucial features and combined them with back propagation neural networks (BPNN) and support vector machines (SVM) to establish the prediction model. The crucial features obtained are as follows: reduction of the intervertebral disc height, age, blood pressure difference, leg pain, gender, etc. Among the models predicting whether patients with LSS ultimately underwent surgical treatment, the model combining LGR and the decision tree for feature selection with a BPNN has a testing accuracy rate of 94.87%, sensitivity of 0.9, specificity of 1, and area under the receiver operating characteristic curve of 0.952. Adopting these data mining techniques to predict whether patients with LSS who opted for conservative treatment ultimately underwent surgical treatment may assist medical professionals in reaching a treatment decision and provide clearer treatment. This may effectively mitigate disease progression, aid the goals of precision medicine, and ultimately enhance the quality of health care.
Abstract Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in ...adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA‐seq to reveal sex‐dependent patterns in IUGR‐induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast‐driven T cell conversion into an immune‐adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non‐immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over‐expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.
Differentiating between early malignancy and benign lesions in oral cavities is difficult using current optical tools. As has been shown in previous studies, microvascular changes in squamous ...epithelium can be regarded as a key marker for diagnosis. We propose the combination of structural and vascular optical coherence tomography (OCT) imaging for the investigation of disease related changes. Progressive thickness changes of epithelium and the destruction of underlying lamina propria was observed during cancer development in a 4- nitroquinoline-1-oxide (4NQO) mouse model. At the same time, microvascular changes in hyperplasia, dysplasia, carcinoma in situ and advanced cancer were observed. Findings from OCT imaging were compared with histology.
The nucleoprotein (NP) of the influenza virus exists as trimers, and its tail-loop binding pocket has been suggested as a potential target for antiinfluenza therapeutics. The possibility of NP as a ...drug target was validated by the recent reports that nucleozin and its analogs can inhibit viral replication by inducing aggregation of NP trimers. However, these inhibitors were identified by random screening, and the binding site and inhibition mechanism are unclear. We report a rational approach to target influenza virus with a new mechanism—disruption of NP–NP interaction. Consistent with recent work, E339A, R416A, and deletion mutant Δ402–428 were unable to support viral replication in the absence of WT NP. However, only E339A and R416A could form hetero complex with WT NP, but the complex was unable to bind the RNA polymerase, leading to inhibition of viral replication. These results demonstrate the importance of the E339…R416 salt bridge in viral survival and establish the salt bridge as a sensitive antiinfluenza target. To provide further support, we showed that peptides encompassing R416 can disrupt NP–NP interaction and inhibit viral replication. Finally we performed virtual screening to target E339…R416, and some small molecules identified were shown to disrupt the formation of NP trimers and inhibit replication of WT and nucleozin-resistant strains. This work provides a new approach to design antiinfluenza drugs.
The nucleoprotein (NP) of the influenza virus exists as trimers, and its tail-loop binding pocket has been suggested as a potential target for antiinfluenza therapeutics. The possibility of NP as a ...drug target was validated by the recent reports that nucleozin and its analogs can inhibit viral replication by inducing aggregation of NP trimers. However, these inhibitors were identified by random screening, and the binding site and inhibition mechanism are unclear. We report a rational approach to target influenza virus with a new mechanism—disruption of NP–NP interaction. Consistent with recent work, E339A, R416A, and deletion mutant Δ402–428 were unable to support viral replication in the absence of WT NP. However, only E339A and R416A could form hetero complex with WT NP, but the complex was unable to bind the RNA polymerase, leading to inhibition of viral replication. These results demonstrate the importance of the E339...R416 salt bridge in viral survival and establish the salt bridge as a sensitive antiinfluenza target. To provide further support, we showed that peptides encompassing R416 can disrupt NP–NP interaction and inhibit viral replication. Finally we performed virtual screening to target E339...R416, and some small molecules identified were shown to disrupt the formation of NP trimers and inhibit replication of WT and nucleozin-resistant strains. This work provides a new approach to design antiinfluenza drugs.
Background. Research investigating the effect of air pollution on diabetes incidence is mostly conducted in Europe and the United States and often produces conflicting results. The link between ...meteorological factors and diabetes incidence remains to be explored. We aimed to explore associations between air pollution and diabetes incidence and to estimate the nonlinear and lag effects of meteorological factors on diabetes incidence. Methods. Our study included 19,000 people aged ≥60 years from the Binhai New District without diabetes at baseline. The generalized additive model (GAM) and the distributed lag nonlinear model (DLNM) were used to explore the effect of air pollutants and meteorological factors on the incidence of diabetes. In the model combining the GAM and DLNM, the impact of each factor (delayed by 30 days) was first observed separately to select statistically significant factors, which were then incorporated into the final multivariate model. The association between air pollution and the incidence of diabetes was assessed in subgroups based on age, sex, and body mass index (BMI). Results. We found that cumulative RRs for diabetes incidence were 1.026 (1.011-1.040), 1.019 (1.012-1.026), and 1.051 (1.019-1.083) per 10 μg/m3 increase in PM2.5, PM10, and NO2, respectively, as well as 1.156 (1.058-1.264) per 1 mg/m3 increase in CO in a single-pollutant model. Increased temperature, excessive humidity or dryness, and shortened sunshine duration were positively correlated with the incidence of diabetes in single-factor models. After adjusting for temperature, humidity, and sunshine, the risk of diabetes increased by 9.2% (95% confidence interval (CI):2.1%-16.8%) per 10 μg/m3 increase in PM2.5. We also found that women, the elderly (≥75 years), and obese subjects were more susceptible to the effect of PM2.5. Conclusion. Our data suggest that PM2.5 is positively correlated with the incidence of diabetes in the elderly, and the relationship between various meteorological factors and diabetes in the elderly is nonlinear.
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