Long non-coding RNA LIP interacts with PARP-1 influencing the efficiency of base excision repair.

In recent years, various long non-coding RNAs (lncRNAs) involved in DNA damage response (DDR) have been identified and studied to deepen our understanding. However, there are rare reports on the association between lncRNAs and base excision repair (BER). Our designed DNA microarray identified dozens of functionally unknown lncRNAs, and their transcription levels significantly increased upon exposure to DNA damage inducers. One of them, named LIP (Long noncoding RNA Interacts with PARP-1), exhibited a significant alteration in transcription in response to methyl methanesulfonate (MMS) and temozolomide (TMZ) treatments. LIP knockdown or knockout cell lines are sensitive to MMS and TMZ, indicating that LIP plays a crucial role in DDR. The loss or insufficiency of LIP significantly influences the efficiency of BER in human cells, and it suggests that LIP participates in the BER pathway. The interaction between LIP and a key factor in BER, poly (ADP-ribose) polymerase 1 (PARP-1), has been confirmed. We identified and characterized LIP, a lncRNA, which is involved in DDR, significantly influences BER efficiency, and interacts with the BER key factor PARP-1. This advances our understanding of the connection between lncRNAs and BER, presenting the potential for the discovery of new drug targets.

Tanshinone IIA Facilitates Efficient Cartilage Regeneration under Inflammatory Factors Caused Stress via Upregulating LncRNA NEAT1_2.

(1) Background: Osteoarthritis (OA) is a crippling condition characterized by chondrocyte dedifferentiation, cartilage degradation, and subsequent cartilage defects. Unfortunately, there is a lack of effective medicines to facilitate the repair of cartilage defects in OA patients. In this study, we investigated the role of lncRNA NEAT1_2 in maintaining the chondrocyte phenotype and identified tanshinone IIA(TAN) as a natural medicine that enhances NEAT1_2 levels, resulting in efficient cartilage regeneration under inflammatory cytokines. (2) Methods: The transcriptional levels of NEAT1_2 and cartilage phenotype-related genes were identified by RT-qPCR. The siRNA interference approach was utilized to silence NEAT1_2; the Alamar Blue assay was performed to determine chondrocyte viability under inflammatory conditions. To evaluate the concentrations of collagen type II and glycosaminoglycans distributed by chondrocytes in vitro and in vivo, immunohistochemical staining and Safranin O staining were used. (3) Results: IL-1ß suppresses NEAT1_2 and genes related to the chondrocytic phenotype, whereas TAN effectively upregulates them in a NEAT1_2-dependent manner. Consistently, TAN alleviated chondrocyte oxidative stress inhibited cartilage degradation by modulating the relevant genes and promoted efficient cartilage regeneration in vitro and in vivo when chondrocytes are exposed to inflammatory cytokines. (4) Conclusions: TAN enhances the expression of NEAT1_2 inhibited by IL-1ß and affects the transcription of chondrocytic phenotype-related genes, which promotes cartilage regeneration in an inflammatory environment.

A preliminary evaluation of targeted nanopore sequencing technology for the detection of Mycobacterium tuberculosis in bronchoalveolar lavage fluid specimens.

Objective: To evaluate the efficacy of targeted nanopore sequencing technology for the detection of Mycobacterium tuberculosis(M.tb.) in bronchoalveolar lavage fluid(BALF) specimens. Methods: A prospective study was used to select 58 patients with suspected pulmonary tuberculosis(PTB) at Henan Chest Hospital from January to October 2022 for bronchoscopy, and BALF specimens were subjected to acid-fast bacilli(AFB) smear, Mycobacterium tuberculosis MGIT960 liquid culture, Gene Xpert MTB/RIF (Xpert MTB/RIF) and targeted nanopore sequencing (TNS) for the detection of M.tb., comparing the differences in the positive rates of the four methods for the detection of patients with different classifications. Results: Among 58 patients with suspected pulmonary tuberculosis, there were 48 patients with a final diagnosis of pulmonary tuberculosis. Using the clinical composite diagnosis as the reference gold standard, the sensitivity of AFB smear were 27.1% (95% CI: 15.3-41.8); for M.tb culture were 39.6% (95% CI: 25.8-54.7); for Xpert MTB/RIF were 56.2% (95% CI: 41.2-70.5); for TNS were 89.6% (95% CI: 77.3-96.5). Using BALF specimens Xpert MTB/RIF and/or M.tb. culture as the reference standard, TNS showed 100% (30/30) sensitivity. The sensitivity of NGS for pulmonary tuberculosis diagnosis was significantly higher than Xpert MTB/RIF, M.tb. culture, and AFB smear. Besides, P values of <0.05 were considered statistically significant. Conclusion: Using a clinical composite reference standard as a reference gold standard, TNS has the highest sensitivity and consistency with clinical diagnosis, and can rapidly and efficiently detect PTB in BALF specimens, which can aid to improve the early diagnosis of suspected tuberculosis patients.

Effect of visceral fat area on the accuracy of preoperative CT-N staging of colorectal cancer.

OBJECTIVE: To investigate the effect of visceral fat area (VFA) on the accuracy of preoperative CT-N staging of colorectal cancer. METHODS: We retrospectively reviewed the clinical and imaging data of 385 CRC patients who underwent surgical resection for colorectal cancer between January 2018 and July 2021. Preoperative CT-N staging and imaging features were determined independently by two radiologists. Using postoperative pathology as the gold standard, patients were divided into accurately and incorrectly staged groups, and clinical and imaging characteristics were compared between the two groups. VFA and subcutaneous fat area (SFA) at the L3 vertebral level, sex, age, BMI, tumor location, size, and tumor circumference ratio (TCR) were included. Logistic regression analysis was used to evaluate the independent factors influencing the accuracy of preoperative N staging of colorectal cancer. RESULTS: Of the 385 patients enrolled, 259 (67.27%) were in the preoperative N-stage accurate staging group, and 126 (32.73%) were in the incorrectly staged group. Univariate analysis showed that there were significant differences in BMI, tumor location, VFA, SFA, size and TCR between the two groups (P<0.05). Logistic regression analysis showed that VFA (95% CI: 1.277, 3.813; P=0.005) and TCR (95% CI: 1.649, 17.545; P=0.005) were independent factors affecting the accuracy of N staging. The optimal cutoff points for VFA and TCR in predicting incorrect staging were 110 cm2 and 0.675, respectively. CONCLUSIONS: Colorectal cancer patients with lower VFA and higher TCR and preoperative CT-N staging had an increased risk for diagnostic errors.

The involvement of ADAR1 in chronic unpredictable stress-induced cognitive impairment by targeting DARPP-32 with miR-874-3p in BALB/c mice.

Introduction: Chronic stress exposure is the main environmental factor leading to cognitive impairment, but the detailed molecular mechanism is still unclear. Adenosine Deaminase acting on double-stranded RNA1(ADAR1) is involved in the occurrence of chronic stress-induced cognitive impairment. In addition, dopamine and Adenosine 3'5'-monophosphate-regulated phospho-protein (DARPP-32) gene variation affects cognitive function. Therefore, we hypothesized that ADAR1 plays a key role in chronic stress-induced cognitive impairment by acting on DARPP-32. Methods: In this study, postnatal 21-day-old male BALB/c mice were exposed to chronic unpredictable stressors. After that, the mice were treated with ADAR1 inducer/inhibitor. The cognitive ability and cerebral DARPP-32 protein expression of BALB/c mice were evaluated. In order to explore the link between ADAR1 and DARPP-32, the effects of ADAR1 high/low expression on DARPP-32 protein expression in vitro were detected. Results: ADAR1 inducer alleviates cognitive impairment and recovers decreased DARPP-32 protein expression of the hippocampus and prefrontal cortex in BALB/c mice with chronic unpredictable stress exposure. In vivo and in vitro studies confirm the results predicted by bio-informatics; that is, ADAR1 affects DARPP-32 expression via miR-874-3p. Discussion: The results in this study demonstrate that ADAR1 affects the expression of DARPP-32 via miR-874-3p, which is involved in the molecular mechanism of pathogenesis in chronic unpredictable stress-induced cognitive impairment. The new findings of this study provide a new therapeutic strategy for the prevention and treatment of stress cognitive impairment from epigenetics.

Segmentation Method of Cerebral Aneurysms Based on Entropy Selection Strategy.

The segmentation of cerebral aneurysms is a challenging task because of their similar imaging features to blood vessels and the great imbalance between the foreground and background. However, the existing 2D segmentation methods do not make full use of 3D information and ignore the influence of global features. In this study, we propose an automatic solution for the segmentation of cerebral aneurysms. The proposed method relies on the 2D U-Net as the backbone and adds a Transformer block to capture remote information. Additionally, through the new entropy selection strategy, the network pays more attention to the indistinguishable blood vessels and aneurysms, so as to reduce the influence of class imbalance. In order to introduce global features, three continuous patches are taken as inputs, and a segmentation map corresponding to the central patch is generated. In the inference phase, using the proposed recombination strategy, the segmentation map was generated, and we verified the proposed method on the CADA dataset. We achieved a Dice coefficient (DSC) of 0.944, an IOU score of 0.941, recall of 0.946, an F2 score of 0.942, a mAP of 0.896 and a Hausdorff distance of 3.12 mm.

Intracranial Aneurysm Rupture Risk Estimation With Multidimensional Feature Fusion.

The rupture of aneurysms is the main cause of spontaneous subarachnoid hemorrhage (SAH), which is a serious life-threatening disease with high mortality and permanent disability rates. Therefore, it is highly desirable to evaluate the rupture risk of aneurysms. In this study, we proposed a novel semiautomatic prediction model for the rupture risk estimation of aneurysms based on the CADA dataset, including 108 datasets with 125 annotated aneurysms. The model consisted of multidimensional feature fusion, feature selection, and the construction of classification methods. For the multidimensional feature fusion, we extracted four kinds of features and combined them into the feature set, including morphological features, radiomics features, clinical features, and deep learning features. Specifically, we applied the feature extractor 3D EfficientNet-B0 to extract and analyze the classification capabilities of three different deep learning features, namely, no-sigmoid features, sigmoid features, and binarization features. In the experiment, we constructed five distinct classification models, among which the k-nearest neighbor classifier showed the best performance for aneurysm rupture risk estimation, reaching an F2-score of 0.789. Our results suggest that the full use of multidimensional feature fusion can improve the performance of aneurysm rupture risk assessment. Compared with other methods, our method achieves the state-of-the-art performance for aneurysm rupture risk assessment methods based on CADA 2020.

Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1.

Adenosine deaminase acting on RNA1 (ADAR1) is a newly discovered epigenetic molecule marker that is sensitive to environmental stressors. A recent study has demonstrated that ADAR1 affects BDNF expression via miR-432 and is involved in antidepressant action. However, the detailed molecular mechanism is still unclear. We have uncovered a new molecular mechanism showing the involvement of miR-432 and circ_0000418 in mediating the antidepressant action of ADAR1. We demonstrate that the ADAR1 inducer (IFN-γ) alleviates the depressive-like behaviors of BALB/c mice treated with chronic unpredictable stress (CUS) exposure. Moreover, both in vivo and in vitro studies show that ADAR1 differently impacts miR-432 and circ_0000418 expressions. Furthermore, the in vitro results demonstrate that circ_0000418 oppositely affects BDNF expression. Together, our results indicate that ADAR1 affects CUS-induced depressive-like behavior and BDNF expression by acting on miR-432 and circ_0000418. Elucidation of this new molecular mechanism will not only provide insights into further understanding the important role of ADAR1 in stress-induced depressive-like behavior but also suggest a potential therapeutic strategy for developing novel anti-depressive drugs.

Polyamines improve K+/Na+ homeostasis in barley seedlings by regulating root ion channel activities.

Polyamines are known to increase in plant cells in response to a variety of stress conditions. However, the physiological roles of elevated polyamines are not understood well. Here we investigated the effects of polyamines on ion channel activities by applying patch-clamp techniques to protoplasts derived from barley (Hordeum vulgare) seedling root cells. Extracellular application of polyamines significantly blocked the inward Na(+) and K(+) currents (especially Na(+) currents) in root epidermal and cortical cells. These blocking effects of polyamines were increased with increasing polycation charge. In root xylem parenchyma, the inward K(+) currents were blocked by extracellular spermidine, while the outward K(+) currents were enhanced. At the whole-plant level, the root K(+) content, as well as the root and shoot Na(+) levels, was decreased significantly by exogenous spermidine. Together, by restricting Na(+) influx into roots and by preventing K(+) loss from shoots, polyamines were shown to improve K(+)/Na(+) homeostasis in barley seedlings. It is reasonable to propose that, therefore, elevated polyamines under salt stress should be a self-protecting response for plants to combat detrimental consequences resulted from imbalance of Na(+) and K(+).