Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis.

Background: Telomere length, crucial for genomic stability, have been implicated in various inflamm-aging diseases, but their role in sarcoidosis remains unexplored. Objective: This study aims to explore the casual effects between TL and sarcoidosis via a bidirectional Mendelian Randomization (MR) study. Methods: We examined single nucleotide polymorphisms (SNPs) associated with TL and sarcoidosis, utilizing available open-access genome-wide association study (GWAS) databases from the UK Biobank and FinnGen. We employed five MR techniques, including Inverse Variance Weighted (IVW), MR Egger, weighted median (WM), Robust adjusted profile score (RAPS), and Maximum likelihood, to assess causal relationships and explore pleiotropy. Results: Summary data extracted from GWAS datasets of TL (n = 472,174) and (n = 217,758) of European ancestry. Employing 130 SNPs with genome-wide significance as instrumental factors for TL, we detect a significant negative correlation between TL and sarcoidosis (OR: 0.682, 95% confidence interval: 0.524-0.888, p : 0.0045). Similarly, utilizing 6 SNPs with genome-wide significance as instrumental factors for sarcoidosis, we fail to identify a noteworthy association between sarcoidosis and TL (OR: 0.992, 95% confidence interval: 0.979-1.005, p : 0.2424). Conclusion: Our results suggest that longer telomeres may reduce the risk of sarcoidosis, highlighting TL as a potential biomarker for diagnosis and long-term monitoring. Understanding the critical role of telomere shortening enables more effective focus on diagnosing, treating, and curing sarcoidosis linked to telomeres. Clinical investigations into treatments that enhance TL are warranted.

Evolution of Chatbots in Nursing Education: Narrative Review.

Background: The integration of chatbots in nursing education is a rapidly evolving area with potential transformative impacts. This narrative review aims to synthesize and analyze the existing literature on chatbots in nursing education. Objective: This study aims to comprehensively examine the temporal trends, international distribution, study designs, and implications of chatbots in nursing education. Methods: A comprehensive search was conducted across 3 databases (PubMed, Web of Science, and Embase) following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. Results: A total of 40 articles met the eligibility criteria, with a notable increase of publications in 2023 (n=28, 70%). Temporal analysis revealed a notable surge in publications from 2021 to 2023, emphasizing the growing scholarly interest. Geographically, Taiwan province made substantial contributions (n=8, 20%), followed by the United States (n=6, 15%) and South Korea (n=4, 10%). Study designs varied, with reviews (n=8, 20%) and editorials (n=7, 18%) being predominant, showcasing the richness of research in this domain. Conclusions: Integrating chatbots into nursing education presents a promising yet relatively unexplored avenue. This review highlights the urgent need for original research, emphasizing the importance of ethical considerations.

Neurotoxic lesions of the anterior claustrum influence cued fear memory in rats.

Background: The claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied. Methods: We evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats. Results: We found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test. Conclusion: These data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions.

[Research Progress in Nucleus Pulposus Tissue Engineering in Lumbar Intervertebral Disc].

Lumbar intervertebral disc degeneration is a common pathological process in the spine,with the main clinical symptoms of low back pain,numbness of lower limbs,and defecation dysfunction.The occurrence and development of lumbar intervertebral disc degeneration are determined by multiple factors,and the pathophysiological and cellular mechanisms remain to be fully understood.Nucleus pulposus tissue engineering is a new biotherapy that combines biological histology with material science to treat diseases including lumbar intervertebral disc degeneration.Clinicians should fully learn the complex relationship between nucleus pulposus tissue engineering and lumbar intervertebral disc degeneration,which will facilitate the clinical treatment of lumbar intervertebral disc degeneration,the rehabilitation of lumbar intervertebral disc after treatment,and the prevention of this disease in the population.

Neurobiology of Stress-Induced Nicotine Relapse.

Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, the relapse rate remains very high. Among the factors that could induce nicotine relapse, stress might be the most important one. In the last decades, preclinical studies have generated many new findings that lead to a better understanding of stress-induced relapse of nicotine-seeking. Several molecules such as α3ß4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated receptor 1, and neuropeptide systems (corticotropin-releasing factor and its receptors, dynorphine and kappa opioid receptor) have been linked to stress-induced nicotine relapse. In this review, we discuss recent advances in the neurobiology, treatment targets, and potential therapeutics of stress-induced nicotine relapse. We also discuss some factors that may influence stress-induced nicotine relapse and that should be considered in future studies. In the final section, a perspective on some research directions is provided. Further investigation on the neurobiology of stress-induced nicotine relapse will shed light on the development of new medicines for controlling smoking and will help us understand the interactions between the stress and reward systems in the brain.

Identification of squalene epoxidase in triterpenes biosynthesis in Poria cocos by molecular docking and CRISPR-Cas9 gene editing.

BACKGROUND: Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids. RESULT: In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. The sgRNA were designed based on the active site residues. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. The results showed that deletion of PcSE inhibited triterpene synthesis. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach. CONCLUSION: The findings from this study provide a foundation for further studies on heterologous biosynthesis of P. cocos secondary metabolites.

Advancing the frontiers of colorectal cancer treatment: harnessing ferroptosis regulation.

In recent years, colorectal cancer incidence and mortality have increased significantly due to poor lifestyle choices. Despite the development of various treatments, their effectiveness against advanced/metastatic colorectal cancer remains unsatisfactory due to drug resistance. However, ferroptosis, a novel iron-dependent cell death process induced by lipid peroxidation and elevated reactive oxygen species (ROS) levels along with reduced activity of the glutathione peroxidase 4 (GPX4) antioxidant enzyme system, shows promise as a therapeutic target for colorectal cancer. This review aims to delve into the regulatory mechanisms of ferroptosis in colorectal cancer, providing valuable insights into potential therapeutic approaches. By targeting ferroptosis, new avenues can be explored for innovative therapies to combat colorectal cancer more effectively. In addition, understanding the molecular pathways involved in ferroptosis may help identify biomarkers for prognosis and treatment response, paving the way for personalized medicine approaches. Furthermore, exploring the interplay between ferroptosis and other cellular processes can uncover combination therapies that enhance treatment efficacy. Investigating the tumor microenvironment's role in regulating ferroptosis may offer strategies to sensitize cancer cells to cell death induction, leading to improved outcomes. Overall, ferroptosis presents a promising avenue for advancing the treatment of colorectal cancer and improving patient outcomes.

[Levels and Clinical Significances of sPD-1 and sPD-L1 in Peripheral Blood of Lymphoma Patients].

OBJECTIVE: To observe the levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death ligand 1 (sPD-L1) in peripheral blood of lymphoma patients, and reveal their clinical significances. METHODS: The peripheral blood specimens and clinical data of 64 newly diagnosed lymphoma patients and 30 healthy volunteers were collected. The levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA), and their correlations with clinical characteristics of the patients including pathological type, stage, lactate dehydrogenase (LDH) level, T cell subsets were analyzed. RESULTS: The levels of both sPD-1 and sPD-L1 in peripheral blood of lymphoma patients were higher than those of normal controls (P <0.05). There were no significant differences in sPD-1 and sPD-L1 levels in peripheral blood between Hodgkin lymphoma and non-Hodgkin lymphoma patients. Different pathological subtypes of lymphoma had different levels of sPD-1. The level of sPD-1 in patients with T-cell lymphoma was higher than that in patients with B-cell lymphoma (P =0.001). The levels of both sPD-1 and sPD-L1 in patients with Ann Arbor stage III and IV were higher than those in patients with stage I and II (P <0.05). The level of sPD-L1 in patients with abnormally increased LDH was higher than that in patients with normal LDH (P =0.001), but there was no significant difference in sPD-1 level. T cell subset analysis showed that the level of sPD-L1 was negatively correlated to CD4+ T cell content (r =-0.265). CONCLUSION: The levels of sPD-1 and sPD-L1 in peripheral blood of lymphoma patients are related to the pathological type, Ann Arbor stage, LDH content and T cell subsets, and will be potential biomarkers in predicting the prognosis of lymphoma.

NIR-II Responsive Nanohybrids Incorporating Thermosensitive Hydrogel as Sprayable Dressing for Multidrug-Resistant-Bacteria Infected Wound Management.

Developing an effective dressing against bacterial infection and synchronously addressing wound complications, such as bleeding, long-term inflammation, and reinfection, are highly desirable in clinical practice. In this work, a second near-infrared (NIR-II) responsive nanohybrid consisting of imipenem encapsulated liposome with gold-shell and lipopolysaccharide (LPS)-targeting aptamer, namely ILGA, is constructed for bacteria elimination. Benefiting from the delicate structure, ILGA exhibits strong affinity and a reliable photothermal/antibiotic therapeutic effect toward multidrug-resistant Pseudomonas aeruginosa (MDR-PA). Furthermore, by incorporating ILGA with a thermosensitive hydrogel poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA), a sprayable dressing ILGA@Gel was prepared, which enables a quick on-demand gelation (10 s) for wound hemostasis and offers excellent photothermal/antibiotic efficacy to sterilize the infected wound. Additionally, ILGA@Gel provides satisfactory wound-healing environments by reeducating wound-associated macrophages for inflammation alleviation and forming a gel layer to block exogenous bacterial reinfection. This biomimetic hydrogel reveals excellent bacteria eradication and wound recovery effectiveness, demonstrating its promising potential for managing complicated infected wounds.

Protecting public's wellbeing against COVID-19 infodemic: The role of trust in information sources and rapid dissemination and transparency of information over time.

Objectives: This study examined how trust in the information about COVID-19 from social media and official media as well as how the information was disseminated affect public's wellbeing directly and indirectly through perceived safety over time. Methods: Two online surveys were conducted in China, with the first survey (Time1, N = 22,718) being at the early stage of the pandemic outbreak and the second one (Time 2, N = 2,901) two and a half years later during the zero-COVID policy lockdown period. Key measured variables include trust in official media and social media, perceived rapid dissemination and transparency of COVID-19-related information, perceived safety, and emotional responses toward the pandemic. Data analysis includes descriptive statistical analysis, independent samples t-test, Pearson correlations, and structural equation modeling. Results: Trust in official media, perceived rapid dissemination and transparency of COVID-19-related information, perceived safety, as well as positive emotional response toward COVID-19 increased over time, while trust in social media and depressive response decreased over time. Trust in social media and official media played different roles in affecting public's wellbeing over time. Trust in social media was positively associated with depressive emotions and negatively associated with positive emotion directly and indirectly through decreased perceived safety at Time 1. However, the negative effect of trust in social media on public's wellbeing was largely decreased at Time 2. In contrast, trust in official media was linked to reduced depressive response and increased positive response directly and indirectly through perceived safety at both times. Rapid dissemination and transparency of COVID-19 information contributed to enhanced trust in official media at both times. Conclusion: The findings highlight the important role of fostering public trust in official media through rapid dissemination and transparency of information in mitigating the negative impact of COVID-19 infodemic on public's wellbeing over time.

Geographical region traceability of Poria cocos and correlation between environmental factors and biomarkers based on a metabolomic approach.

The edible values of P. cocos from different origins vary significantly, therefore, it is important to investigate the traceability of geographical regions and identify the geographical biomarkers of P. cocos. The metabolites of P. cocos of the different geographical origins were assessed using liquid chromatography tandem-mass spectrometry, principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). The OPLS-DA could clearly discriminate the metabolites of P. cocos from the three cultivation regions (YN, Yunnan; AH, Anhui; JZ, Hunan). Finally, three carbohydrates, four amino acids, and four triterpenoids were selected as biomarkers for P. cocos origin tracing. Correlation matrix analysis revealed that the contents of biomarkers were closely related to geographical origin. Altitude, temperature, and soil fertility were the main factors responsible for the differences in biomarker profiles in P. cocos. The metabolomics approach provides an effective strategy for tracing and identifying the biomarkers of P. cocos from different geographical origins.

Insights into the metabolic profiling of Polygonati Rhizoma fermented by Lactiplantibacillus plantarum under aerobic and anaerobic conditions using a UHPLC-QE-MS/MS system.

Introduction: Polygonati Rhizoma is a multi-purpose food with medicinal uses. Fermentation of Polygonati Rhizoma by lactic acid bacteria could provide new insights into the development of Polygonati Rhizoma products. Methods: In this study, Lactiplantibacillus plantarum was fermented with Polygonati Rhizoma extracts in a bioreactor under aerobic and anaerobic conditions with pH and DO real-time detection. Metabolic profiling was determined by UHPLC-QE-MS/MS system. Principal component analysis and orthogonal partial least-squares discriminant analysis were used to perform multivariate analysis. Results: A total of 98 differential metabolites were identified in broth after fermentation, and 36 were identified between fermentation under aerobic and anaerobic conditions. The main metabolic pathways in the fermentation process are ABC transport and amino acid biosynthesis. Most of the compounds such as L-arginine, L-aspartic acid, leucine, L-lysine, citrate, inosine, carnitine, betaine, and thiamine were significantly increased during fermentation, playing a role in enhancing food flavor. Compared with anaerobic fermentation, aerobic conditions led to a significant rise in the levels of some compounds such as valine, isoleucine, and glutamate; this increase was mainly related to branched-chain amino acid transaminase, isocitrate dehydrogenase, and glutamate dehydrogenase. Discussion: Aerobic fermentation is more beneficial for the fermentation of Polygonati Rhizoma by L. plantarum to produce flavor and functional substances. This study is the first report on the fermentation of Polygonati Rhizoma by L. plantarum and provides insights that would be applicable in the development of Polygonati Rhizoma fermented products.

Genome editing in the edible fungus Poria cocos using CRISPR-Cas9 system integrating genome-wide off-target prediction and detection.

Poria cocos is an important edible and medicinal fungus with a long history. However, the lack of adequate genetic tools has hindered molecular genetic research and the genetic modification of this species. In this study, the endogenous U6 promoters were identified by mining data from the P. cocos genome, and the promoter sequence was used to construct a sgRNA expression vector pFC332-PcU6. Then, the protoplast isolation protocol was developed, and the sgRNA-Cas9 vector was successfully transformed into the cells of P. cocos via PEG/CaCl2-mediated transformation approach. Off-target sites were genome-widely predicted and detected. As a result, the target marker gene ura3 was successfully disrupted by the CRISPR-Cas9 system. This is the first report of genome editing in P. cocos using CRISPR-Cas9 system integrating genome-wide off-target prediction and detection. These data will open up new avenues for the investigation of genetic breeding and commercial production of edible and medicinal fungus.

Effect of the R126C mutation on the structure and function of the glucose transporter GLUT1: A molecular dynamics simulation study.

Glucose transporter 1 (GLUT1) is responsible for basal glucose uptake and is expressed in most tissues under normal conditions. GLUT1 mutations can cause early-onset absence epilepsy and myoclonus dystonia syndrome (MDS), with MDS potentially lethal. In this study, the effect of the R126C mutation, which is associated with MDS, on structural stability and substrate transport of GLUT1 was investigated. Various bioinformatics tools were used to predict the stability of GLUT1, revealing that the R126C mutation reduces the structural stability of GLUT1. Molecular dynamics (MD) simulations were used to further characterize the effect of the R126C mutation on GLUT1 structural stability. Based on the MD simulations, specific conformational changes and dominant motions of the GLUT1 mutant were characterized by Principal component analysis (PCA). The mutation disrupts hydrogen bonds between substrate-binding residues and glucose, thus likely reducing substrate affinity. The R126C mutation reduces the conformational stability of the protein, and fewer intramolecular hydrogen bonds were present in the mutated GLUT1 when compared with that of wild-type GLUT1. The mutation increased the free energy of glucose transport through GLUT1 significantly, especially at the mutation site, indicating that passage of glucose through the channel is hindered, and this mutant may even release cytoplasmic glucose. This study provides a detailed atomic-level explanation for the reduced structural stability and substrate transport capacity of a GLUT1 mutant. The results aid our understanding of the structure of GLUT1 and provide a framework for developing drugs to treat GLUT1-related diseases, such as MDS.

Variation of plantaris muscle: a case report with clinical significance / Variación del músculo plantar: reporte de un caso con significado clínico

SUMMARY: The plantaris muscle is located between the soleus and gastrocnemius muscles, within the posterior calf group. Due to degeneration and its loss of plantar-flexion function, the muscle is vestigial in human beings, but it retains clinical significance. Few cases of variation in the plantaris muscle have been reported, and this, therefore, appears to be rare. Nonetheless, absence of this muscle was identified via the dissection of a left lower limb (male), which also indicated the absence of an attachment in the usual position. The present report, which addresses such variation, may provide both inspiration and reference points for the clinical treatment of so-called "tennis leg", and for the use of plantaris muscle for the purposes of clinical, autologous graft repair.

RESUMEN: El músculo plantar se ubica entre los músculos sóleo y gastrocnemio, dentro del grupo posterior de la pierna. Debido a la degeneración y la pérdida de la función de flexión plantar, el músculo es un vestigio en los seres humanos, pero conserva su importancia clínica. Se han informado pocos casos de variación en el músculo plantar y, por lo tanto, esto parece ser raro. No obstante, se observó la ausencia de este músculo durante la disección de un miembro inferior izquierdo (masculino). El presente informe, que aborda dicha variación, puede proporcionar puntos de referencia para el tratamiento clínico de la llamada "pierna de tenista" y para el uso del músculo plantar con fines de reparación clínica con injerto autólogo.

Research Note: Preservative effect of compound spices extracts on marinated chicken.

The antimicrobial effect of 21 nature spices essential oils (EOs) on marinated chicken was investigated and response surface analysis was applied to obtain the optimal combination. Cassia bark EO, cinnamon EO, tea tree EO, and angelica EO had the best antibacterial effect. Their inhibition zone diameters (IZD) were 23 mm, 21 mm, 15 mm, and 12 mm, and their minimal bactericidal concentrations (MBC) were 1.25 µL/mL, 1.25 µL/mL, 10.00 µL/mL, 20.00 µL/mL. Using the Box-Behnken Design model, with the minimum total number of spoilage bacteria as the evaluation index, the optimal mixture was cassia bark EO 2.40 µL/mL, cinnamon EO 1.00 µL/mL, tea tree EO 3.50 µL/mL, and angelica EO 9.00 µL/mL. Compared with the control group, the total number of colonies was reduced by 1.3 log unites at the 12th sampling day, and the protein degradation process was slowed down owing to the preservative addition. These results indicate the potential application of nature extracts in chicken and other meat preservation.

Optimization of Different Acid-Catalyzed Pretreatments on Co-Production of Xylooligosaccharides and Glucose from Sorghum Stalk.

There is an increasing emphasis on the transformation of lignocellulosic biomass into versatile products. The feasibility of preparing xylooligosaccharides (XOS) by hydrolysis of sorghum stalk (SS) using organic and inorganic acids was studied. The influences of different acids (gluconic acid, acetic acid, sulfuric acid, and oxalic acid), process time and temperature on the hydrolysis of SS were explored. The findings indicated XOS yield can be maintained at a high level under different conditions with organic acid pretreatments. Optimum yield of XOS (39.4%) was obtained using sulfuric acid (pH 2.2) at 170 °C and 75 min of process time. It is suggested when reaction temperature and time were increased, both X5 and X6 are cracked into XOS with lower molecular mass such as X2, X3, and X4. Moreover, the results based on mass balance showed that up to 110 g (XOS) plus 117 g (glucose) can be recovered from 1000 g of SS. Results will give insights into establishing an efficient acid pretreatment of sorghum stalk to coproduction of XOS and glucose.

Antibacterial Properties and Mechanism of Lysozyme-Modified ZnO Nanoparticles.

The lysozyme-modified nanoparticles (LY@ZnO NPs) were synthesized by the reduction-oxidation method, and the morphology and structure of LY@ZnO were analyzed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microsclope (SEM), and particle size analysis. The antibacterial effects of LY@ZnO against Escherichia coli (E. coli, Gram-negative bacteria) and Staphylococcus aureus (S. aureus, Gram-positive bacteria) were discussed by measuring the zone of inhibition (ZOI) and growth inhibition. The antimicrobial experiments showed that the LY@ZnO NPs possessed better antibacterial activity than ZnO. Besides, the antibacterial mechanism of LY@ZnO was also investigated, which was attributed to the generation of reactive oxygen species (ROS). Furthermore, the toxicities of LY@ZnO in vivo and in vitro were discussed by the cell counting kit-8 method and animal experiments, showing that LY@ZnO possessed excellent biocompatibility. Finally, the therapeutic effect of LY@ZnO on a rat skin infection model caused by methicillin-resistant Staphylococcus aureus (MRSA) was also studied, which exhibited good anti-infective activity. Our findings showed that LY@ZnO possessed remarkable antibacterial ability due to its excellent membrane permeability and small particle size. Besides, LY@ZnO also exhibited certain stability and great safety, which showed tremendous prospects for microbial infection in patients. It would also be helpful for a better understanding of the enzyme-modified nanomaterials against bacteria.

Long non­coding RNA HAND2­AS1/miR­106a/PTEN axis re­sensitizes cisplatin­resistant ovarian cells to cisplatin treatment.

Cisplatin (DDP) resistance in patients suffering from ovarian cancer is a considerable hurdle to successful treatment. The present study aimed to identify a possible long non­coding RNA (lncRNA)­microRNA (miRNA)­mRNA axis participating in ovarian cancer DDP­resistance based on the critical roles of non­coding RNAs, including lncRNAs and miRNAs, in carcinogenesis. According to online data and experimental results, lncRNA HAND2­AS1 expression was significantly downregulated within ovarian carcinoma, especially within recurrent and DDP­resistant ovarian carcinoma. The expression of HAND2­AS1 was also shown to be markedly inhibited in SKOV3/DDP (DDP) cells with resistance to DDP. In SKOV3/DDP cells, HAND2­AS1 overexpression inhibited cell viability and promoted cell apoptosis upon DDP treatment through the Bcl­2/caspase­3 apoptotic signaling. It was hypothesized that PTEN mRNA expression was also markedly inhibited in SKOV3/DDP ovarian cancer cells, while HAND2­AS1 overexpression rescued PTEN proteins and blocked PI3K/AKT signaling activation. Moreover, miR­106a was found to bind directly to PTEN 3' UTR and HAND2­AS1. Upon DDP treatment, miR­106a overexpression in SKOV3/DDP cells promoted cell viability. It inhibited cell apoptosis through the Bcl­2/caspase­3 apoptotic signaling pathway and downregulated the protein levels of PTEN and upregulated PI3K/AKT signaling activity. Furthermore, miR­106a overexpression partially reversed the effect of HAND2­AS1 overexpression upon PTEN proteins and SKOV3/DDP cell proliferation upon DDP treatment. In conclusion, a lncRNA HAND2­AS1/miR­106a/PTEN axis that re­sensitizes DDP­resistant SKOV3/DDP cells to DDP treatment has been established.

Effects of hypoxia on DNA hydroxymethylase Tet methylcytosine dioxygenase 2 in a KG-1 human acute myeloid leukemia cell line and its mechanism.

Hypoxia is involved in the epigenetic modification of leukemia. As an important DNA hydroxymethylase and a tumor suppressor gene, the expression regulating mechanism of Tet methylcytosine dioxygenase 2 (TET2) remains unclear. The aim of the present study was to explore whether hypoxia and hypoxia-inducible factor 1α (HIF-1α) regulate TET2 gene expression and its demethylation function in acute myeloid leukemia (AML). The human AML cell line KG-1 was used in the present study. The results demonstrated that hypoxia could increase proliferation, enhance metabolism and inhibit apoptosis in KG-1 cells, as detected by the cell counting kit-8 assay, lactate dehydrogenase assay and Annexin V-FITC/propidium iodide staining, respectively. Hypoxia reduced the genome methylation status in KG-1 cells detected using 5-methylcytosine and 5-hydroxymethylcytosine detection kits. In addition, HIF-1α overexpression increased TET2 expression, 5-hmC level and cyclin-dependent kinase inhibitor 2B [p15(INK4B)] gene demethylation compared with the HIF-1α non-overexpression group in KG-1 cells detected by reverse transcription-quantitative PCR, western blotting, 5-hydroxymethylcytosine detection kits and methylation-specific PCR, respectively. The inhibition of HIF-1α by inhibitor YC-1 reduced demethylation in KG-1 cells by decreasing TET2 expression. It was also revealed that HIF-1α could enhance TET2 transcriptional activity by binding to the hypoxia response element of the TET2 gene promoter region using chromatin immunoprecipitation and luciferase reporter gene assays. TET2 may be a potential target gene regulated by HIF-1α. Hypoxia was demonstrated to regulate the expression of TET2 by HIF-1α, which in turn affected the methylation and expression of downstream target genes and served a role in the occurrence and progression of leukemia. In the present study, the association between hypoxia metabolism and epigenetic regulation in AML was investigated and the findings provided a new idea and experimental basis for the diagnosis and treatment of hematologic malignancies.