Molecular characterization of porcine reproductive and respiratory syndrome virus identified in 2021 from Nepal.

Porcine reproductive and respiratory syndrome (PRRS), an important viral disease of swine caused by PRRS virus (PRRSV) was first confirmed in Nepal in 2013. Since then, the virus has spread throughout the country and has now become endemic affecting the pig production nationally. However, molecular characterization of circulating strains has not been done in Nepal yet. In the present study, serum samples were collected from outbreak areas of different districts of Nepal and samples positive for PRRSV by ELISA were sent to Animal and Plant Health Agency (APHA), United Kingdom for sequence analysis. Out of 35 samples that were sent to APHA, only one sample was found positive by PCR and subjected to sequence analysis based on ORF5, ORF7 and Nsp2. The results from the phylogenetic analysis demonstrated that the PRRSV strain belongs to PRRSV-2 and lineage 8 strain. The sequences from the Nepalese PRRSV strain revealed a high degree of similarity with the strains isolated from India, China and Vietnam, with the closest genetic relatedness to the Indian isolates from 2020 and 2018. This is the first study on molecular characterization of PRRS virus circulating in Nepal. Further studies on strains circulating in Nepal are very essential to understand the virus diversity, its spread and evolution.

[Retracted] The AMPK­mTOR axis requires increased MALAT1 expression for promoting granulosa cell proliferation in endometriosis.

[This retracts the article DOI: 10.3892/etm.2020.9453.].

Analysis and risk factors of deep vein catheterization-related bloodstream infections in neonates.

To investigate the incidence, risk factors, and pathogenic characteristics of catheter-related bloodstream infection caused by peripherally inserted central venous catheter in neonates, and to provide references for reducing the infection rate of peripherally inserted central venous catheter. The clinical data of 680 neonates who underwent peripherally inserted central catheter (PICC) in the neonatal intensive care unit from June 2020 to June 2023 were retrospectively analyzed. The risk factors and independent risk factors of catheter-related bloodstream infection caused by PICC were determined by univariate and multivariate analysis, respectively. Catheter-related bloodstream infection occurred in 38 of 680 neonates who underwent PICC. The infection rate was 4.74%. The proportions of fungi, gram-positive bacteria, and gram-negative bacteria were 42.11%, 36.84%, and 21.05%, respectively. Candida parapsilosis was the main fungus (18.42%), coagulase negative Staphylococcus was the main gram-positive bacteria (23.68%), and Klebsiella pneumoniae and Escherichia coli were the main gram-negative bacteria (7.89%). Univariate analysis showed that gestational age ≤32 weeks, birth weight ≤1500 g, congenital diseases, nutritional support, catheterization time, 5-minute APGAR score ≤7, and neonatal respiratory distress syndrome were associated with catheter-related bloodstream infection caused by PICC. Multivariate analysis showed that premature delivery, low birth weight, parenteral nutrition, long catheterization time, and 5-minute APGAR score ≤7 were associated with catheter-related bloodstream infection caused by PICC. Among the pathogens detected, there were 6 cases of K pneumoniae, 5 cases of coagulase negative staphylococci, and 2 cases of fungi. Low birth weight, premature delivery, off-site nutrition, long catheterization time, and 5-minute APGAR score ≤7 are independent risk factors for catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters. The pathogenic bacteria are fungi and multidrug-resistant bacteria.

ZNF692 promotes cell proliferation, invasion and migration of human prostate cancer cells by targeting the EMT signaling pathway.

BACKGROUND: Prostate cancer poses a considerable threat to human health. At present, the mechanism of tumor progression remains unclear. ZNF692 is overexpressed in many tumors, and the high expression of ZNF692 is correlated with tumor aggressiveness and tumor phenotype of prostate cancer, suggesting that ZNF692 may play an important role in tumor biology of prostate cancer. This paper aims to elucidate the relationship between them. METHODS: The expression level of ZNF692 was verified in normal prostate cells (RWPE-1) and prostate cancer cells (LNCaP, PC3, DU145). PC3 cells were selected to construct the ZNF692 knockout prostate cancer cell line. The changes of cell proliferation, apoptosis, invasion and metastasis were detected by CCK8, Edu staining, Transwell assay and scratch assay. The expression levels of related proteins were detected by Western blot. RESULTS: At the cellular level, ZNF692 was overexpressed to varying degrees in prostate cancer cell lines, with the highest expression in PC3 cell lines. CCK8 and Edu results showed that the proliferation of prostate cancer PC3 cells that knocked down ZNF692 was slowed. Transwell assay and scratch assay showed reduced invasion and migration of prostate cancer PC3 cells that knocked out ZNF692. Flow cytometry showed that the apoptosis rate of prostate cancer PC3 cells after ZNF692 knockout was increased. In addition, after ZNF692 silencing, the expression level of epithelial phenotype E-cadherin increased in PC3 cells, while the expression level of interstitial phenotype N-cadherin, Vimentin, c-Myc, and CyclinA1 decreased. The state of prostate cancer PC3 cells that overexpressed ZNF692 was reversed from the state after ZNF692 was knocked down. CONCLUSION: ZNF692 can be used as a new prognostic marker and a potential biologic therapeutic target for PCa. By inhibiting the expression of c-myc and cyclinA1, the EMT signaling pathway is regulated to provide evidence for its potential molecular mechanism.

A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells.

Both Manganese (Mn2+) and MSA-2 can activate the downstream signal pathway through stimulator of interferon genes (STING) and induce the expression of type I interferon, which is important for hosts to protect against DNA viruses. However, its effect on RNA viruses remains unknown. In this study, we used Seneca Valley virus (SVV) as a model RNA virus to investigate the inhibitory effects of Mn2+ and MSA-2 on the virus replication in the porcine cells (PK-15 cells). The results showed that both MSA-2 and Mn2+ were able to inhibit the SVV replication in PK-15 cells. The combination of MAS-2 and Mn2+ could confer better protection against SVV. Further studies showed that MSA-2 and Mn2+ could activate TBK1, IRF3 and NFκB through STING and induce the expression of IFN-ß, IL-6 and TNF-α. The present study confirmed that MSA-2 synergized with Mn2+ in STING activation to generate a better antiviral effect in vitro, which would be helpful for the further development of effective antiviral drugs in the future.

Seneca Valley Virus Degrades STING via PERK and ATF6-Mediated Reticulophagy.

Seneca Valley Virus (SVV), a member of the Picornaviridae family, is an emerging porcine virus that can cause vesicular disease in pigs. However, the immune evasion mechanism of SVV remains unclear, as does its interaction with other pathways. STING (Stimulator of interferon genes) is typically recognized as a critical factor in innate immune responses to DNA virus infection, but its role during SVV infection remains poorly understood. In the present study, we observed that STING was degraded in SVV-infected PK-15 cells, and SVV replication in the cells was affected when STING was knockdown or overexpressed. The STING degradation observed was blocked when the SVV-induced autophagy was inhibited by using autophagy inhibitors (Chloroquine, Bafilomycin A1) or knockdown of autophagy related gene 5 (ATG5), suggesting that SVV-induced autophagy is responsible for STING degradation. Furthermore, the STING degradation was inhibited when reticulophagy regulator 1 (FAM134B), a reticulophagy related receptor, was knocked down, indicating that SVV infection induces STING degradation via reticulophagy. Further study showed that in eukaryotic translation initiation factor 2 alpha kinase 3 (PERK)/activating transcription factor 6 (ATF6) deficient cells, SVV infection failed to induce reticulophagy-medaited STING degradation, indicating that SVV infection caused STING degradation via PERK/ATF6-mediated reticulophagy. Notably, blocking reticulophagy effectively hindered SVV replication. Overall, our study suggested that SVV infection resulted in STING degradation via PERK and ATF6-mediated reticulophagy, which may be an immune escape strategy of SVV. This finding improves the understanding of the intricate interplay between viruses and their hosts and provides a novel strategy for the development of novel antiviral drugs.

Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy.

Left ventricular regional wall thickness (LVRWT) is an independent predictor of morbidity and mortality in cardiovascular diseases (CVDs). To identify specific genetic influences on individual LVRWT, we established a novel deep learning algorithm to calculate 12 LVRWTs accurately in 42,194 individuals from the UK Biobank with cardiac magnetic resonance (CMR) imaging. Genome-wide association studies of CMR-derived 12 LVRWTs identified 72 significant genetic loci associated with at least one LVRWT phenotype (P < 5 × 10-8), which were revealed to actively participate in heart development and contraction pathways. Significant causal relationships were observed between the LVRWT traits and hypertrophic cardiomyopathy (HCM) using genetic correlation and Mendelian randomization analyses (P < 0.01). The polygenic risk score of inferoseptal LVRWT at end systole exhibited a notable association with incident HCM, facilitating the identification of high-risk individuals. The findings yield insights into the genetic determinants of LVRWT phenotypes and shed light on the biological basis for HCM etiology.

Chronic Fluoride Exposure Induces Ovarian Dysfunction and Potential Association with Premature Ovarian Failure in Female Rats.

Chronic fluorosis has been widely investigated for its adverse effects on skeletal and neurological health; however, its impact on reproductive health, especially in females, remains underexplored. In this study, female Sprague-Dawley rats were exposed to different fluoride concentrations (0.75, 50, and 100 mg/L) in their drinking water for six months. Dental fluorosis and increased urinary fluoride content were observed in fluoride-exposed rats, reflecting fluoride accumulation and exposure levels. Chronic fluorosis resulted in reduced ovary organ coefficient, indicating harmful effects on ovarian tissue. Additionally, the number of ovarian primordial and primary/secondary follicles decreased, while the number of atresia follicles increased. Furthermore, chronic fluorosis led to disrupted estrous cycles. Hormonal analysis revealed altered secretion of estrogen, progesterone, anti-Müllerian hormone, luteinizing hormone, follicular stimulating hormone, and inhibin B in response to fluoride exposure. Ultrastructural observation of ovarian granulosa cells showed evidence of apoptosis, which was further confirmed by flow cytometry. Caspase-3 activity was increased, and ATP levels were decreased, suggesting mitochondrial impairment and apoptosis induction. The mRNA and protein expression of BMP15 and GDF9, essential regulators of ovarian function, significantly decreased with increasing fluoride concentration. Furthermore, gene expression analysis identified a panel of premature ovarian failure-related genes that were downregulated in fluoride-exposed rat ovaries. These findings suggest that chronic fluoride exposure may contribute to ovarian dysfunction and possibly the pathogenesis of premature ovarian failure. Understanding the toxicological effects of chronic fluoride exposure on ovarian function is essential for identifying potential environmental risk factors affecting female reproductive health.

Genetic Variants That Impact Alternative Polyadenylation in Cancer Represent Candidate Causal Risk Loci.

Alternative polyadenylation (APA) is emerging as a major mechanism of posttranscriptional regulation. APA can impact the development and progression of cancer, suggesting that the genetic determinants of APA might play an important role in regulating cancer risk. Here, we depicted a pan-cancer atlas of human APA quantitative trait loci (apaQTL), containing approximately 0.7 million apaQTLs across 32 cancer types. Systematic multiomics analyses indicated that cancer apaQTLs could contribute to APA regulation by altering poly(A) motifs, RNA-binding proteins (RBP), and chromatin regulatory elements and were preferentially enriched in genome-wide association studies (GWAS)-identified cancer susceptibility loci. Moreover, apaQTL-related genes (aGene) were broadly related to cancer signaling pathways, high mutational burden, immune infiltration, and drug response, implicating their potential as therapeutic targets. Furthermore, apaQTLs were mapped in Chinese colorectal cancer tumor tissues and then screened for functional apaQTLs associated with colorectal cancer risk in 17,789 cases and 19,951 controls using GWAS-ChIP data, with independent validation in a large-scale population consisting of 6,024 cases and 10,022 controls. A multi-ancestry-associated apaQTL variant rs1020670 with a C>G change in DNM1L was identified, and the G allele contributed to an increased risk of colorectal cancer. Mechanistically, the risk variant promoted aberrant APA and facilitated higher usage of DNM1L proximal poly(A) sites mediated by the RBP CSTF2T, which led to higher expression of DNM1L with a short 3'UTR. This stabilized DNM1L to upregulate its expression, provoking colorectal cancer cell proliferation. Collectively, these findings generate a resource for understanding APA regulation and the genetic basis of human cancers, providing insights into cancer etiology. SIGNIFICANCE: Cancer risk is mediated by alternative polyadenylation quantitative trait loci, including the rs1020670-G variant that promotes alternative polyadenylation of DNM1L and increases colorectal cancer risk.

Identification of Potential Gene Targets for Suppressing Oviposition in Holotrichia parallela Using Comparative Transcriptome Analysis.

Holotrichia parallela is an important plant pest. Comparative feeding experiments showed that the egg production, oviposition duration and survival rate of H. parallela beetles were significantly higher when they fed on elm leaves than when they fed on willow or purpus privet leaves. RNA sequencing was used to determine transcriptomic changes associated with oviposition. Comparative transcriptome analysis revealed that the beetles that fed on elm and willow had a total of 171 genes with differential expression. When the beetles fed on elm and purpus privet, 3568 genes had differential expression. The vitellogenesis, ovarian serine protease, odorant-binding proteins, acyl-CoA synthetase and follicle cell proteins were commonly upregulated genes in elm-fed beetles compared with those fed on willow/purpus privet leaves. The involvement of the follicle cell protein 3C gene in the regulation of oviposition was confirmed using RNA interference. The results provide insights into the molecular mechanisms underlying oviposition in H. parallela feeding on different host plants. This study also describes a method for identifying potentially effective genes for pest control.

Evaluative effectiveness of follicular output rate, ovarian sensitivity index, and ovarian response prediction index for the ovarian reserve and response of low-prognosis patients according to the POSEIDON criteria: a retrospective study.

The aim was to explore the implications of follicular output rate (FORT), ovarian sensitivity index (OSI), ovarian response prediction index (ORPI), and follicle-to-oocyte index (FOI) in low-prognosis patients defined by POSEIDON criteria. In total, 4030 fresh in vitro fertilization (IVF) cycles from January 2013 to October 2021 were included in this retrospective cohort analysis and were categorized into four groups based on the POSEIDON criteria. The FORT between Groups 1 and 2 (0.61 ± 0.34 vs. 0.65 ± 0.35, P = 0.081) and Groups 3 and 4 (1.08 ± 0.82 vs. 1.09 ± 0.94, P = 0.899) were similar. The OSI in the order from the highest to the lowest were 3.01 ± 1.46 in Group 1, 2.28 ± 1.09 in Group 2, 1.54 ± 1.04 in Group 3, and 1.34 ± 0.96 in Group 4 (P < 0.001). The trend in the ORPI values was consistent with that in the OSI. FORT, OSI, ORPI, and FOI complemented each other and offered excellent effectiveness in reflecting ovarian reserve and response, but they were not good predictors of clinical pregnancy rate (CPR) from IVF.

Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk.

Genome-wide association studies have identified numerous variants associated with human complex traits, most of which reside in the non-coding regions, but biological mechanisms remain unclear. However, assigning function to the non-coding elements is still challenging. Here we apply Activity-by-Contact (ABC) model to evaluate enhancer-gene regulation effect by integrating multi-omics data and identified 544,849 connections across 20 cancer types. ABC model outperforms previous approaches in linking regulatory variants to target genes. Furthermore, we identify over 30,000 enhancer-gene connections in colorectal cancer (CRC) tissues. By integrating large-scale population cohorts (23,813 cases and 29,973 controls) and multipronged functional assays, we demonstrate an ABC regulatory variant rs4810856 associated with CRC risk (Odds Ratio = 1.11, 95%CI = 1.05-1.16, P = 4.02 × 10-5) by acting as an allele-specific enhancer to distally facilitate PREX1, CSE1L and STAU1 expression, which synergistically activate p-AKT signaling. Our study provides comprehensive regulation maps and illuminates a single variant regulating multiple genes, providing insights into cancer etiology.

Genetic Control of Alternative Splicing and its Distinct Role in Colorectal Cancer Mechanisms.

BACKGROUND & AIMS: Dysregulation of alternative splicing is implicated in many human diseases, and understanding the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of cancers. We aimed to provide a comprehensive functional dissection of splicing quantitative trait loci (sQTLs) in cancer and focus on elucidating its distinct role in colorectal cancer (CRC) mechanisms. METHODS: We performed a comprehensive sQTL analysis to identify genetic variants that control messenger RNA splicing across 33 cancer types from The Cancer Genome Atlas and independently validated in our 154 CRC tissues. Then, large-scale, multicenter, multi-ethnic case-control studies (34,585 cases and 76,023 controls) were conducted to examine the association of these sQTLs with CRC risk. A series of biological experiments in vitro and in vivo were performed to investigate the potential mechanisms of the candidate sQTLs and target genes. RESULTS: The molecular characterization of sQTL revealed its distinct role in cancer susceptibility. Tumor-specific sQTL further showed better response to cancer development. In addition, functionally informed polygenic risk score highlighted the potentiality of sQTLs in the CRC prediction. Complemented by large-scale population studies, we identified that the risk allele (T) of a multi-ancestry-associated sQTL rs61746794 significantly increased the risk of CRC in Chinese (odds ratio, 1.20; 95% CI, 1.12-1.29; P = 8.82 × 10-7) and European (odds ratio, 1.11; 95% CI, 1.07-1.16; P = 1.13 × 10-7) populations. rs61746794-T facilitated PRMT7 exon 16 splicing mediated by the RNA-binding protein PRPF8, thus increasing the level of canonical PRMT7 isoform (PRMT7-V2). Overexpression of PRMT7-V2 significantly enhanced the growth of CRC cells and xenograft tumors compared with PRMT7-V1. Mechanistically, PRMT7-V2 functions as an epigenetic writer that catalyzes the arginine methylation of H4R3 and H3R2, subsequently regulating diverse biological processes, including YAP, AKT, and KRAS pathway. A selective PRMT7 inhibitor, SGC3027, exhibited antitumor effects on human CRC cells. CONCLUSIONS: Our study provides an informative sQTLs resource and insights into the regulatory mechanisms linking splicing variants to cancer risk and serving as biomarkers and therapeutic targets.

Risk SNP in a transcript of RP11-638I2.4 increases lncRNA-YY1 interaction and pancreatic cancer susceptibility.

Tens of thousands of long non-coding RNAs (lncRNAs) have been identified through RNA-seq analysis, but the biological and pathological significance remains unclear. By integrating the genome-wide lncRNA data with a cross-ancestry meta-analysis of PDAC GWASs, we depicted a comprehensive atlas of pancreatic ductal adenocarcinoma (PDAC)-associated lncRNAs, containing 1,204 lncRNA (445 novel lncRNAs and 759 GENCODE annotated lncRNAs) and 4,368 variants. Furthermore, we found that PDAC-associated lncRNAs could function by altering chromatin activity, transcription factors, and RNA-binding proteins binding affinity. Importantly, genetic variants linked to PDAC are preferentially found at PDAC-associated lncRNA regions, supporting the biological and clinical relevance of PDAC-associated lncRNAs. Finally, we prioritized a novel transcript (MICT00000110172.1) of RP11-638I2.4 as a potential tumor promoter. MICT00000110172.1 is able to reinforce the interaction with YY1, which could reverse the effect of YY1 on pancreatic cancer cell cycle arrest to promote the pancreatic cancer growth. G > A change at rs2757535 in the second exon of MICT00000110172.1 induces a spatial structural change and creates a target region for YY1 binding, which enforces the effect of MICT00000110172.1 in an allele-specific manner, and thus confers susceptibility to tumorigenesis. In summary, our results extend the repertoire of PDAC-associated lncRNAs that could act as a starting point for future functional explorations, and the identification of lncRNA-based target therapy.

Determination and Prediction of Time-Varying Parameters of Mooney-Rivlin Model of Rubber Material Used in Natural Rubber Bearing under Alternating of Aging and Seawater Erosion.

In this paper, we examined the parameters of the Mooney-Rivlin model based on the effects of alternative aging and sea corrosion tests for natural rubber bearings and rubber materials in seawater. The model parameters for rubber material used in natural rubber bearings were determined using the least-squares method. Meanwhile, the time-varying law formula of the Mooney-Rivlin model parameters of rubber were fitted, and the fitting and calculated values were compared. Both fitting values and calculated values coincide with each other well. Then, the rubber material parameters were predicted based on the calculated results and combined with nonlinear auto-regressive (NAR). The predicted values were compared with both the fitting and calculated values. The average deviations between predicted and fitting values for C10 and C01 were 2.6% and 5.1%, respectively, and average deviations between predicted and calculated values for C10 and C01 were 5.2% and 4.1%. Compared results show that the predicted values are in good agreement with both the fitting and calculated values; meanwhile, the proposed time-varying law formula of the Mooney-Rivlin model parameters of rubber material have been well verified.

The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca2+-CamkII/Ampk axis.

China has the world's largest reserves of rare earth elements (REEs), but widespread mining and application of REEs has led to an increased risk of potential pollution. Yttrium (Y), the first heavy REEs to be discovered, poses a substantial threat to human health. Unfortunately, little attention has been given to the impact of Y on human reproductive health. In this study, we investigated the toxic effects of YCl3 on mouse testes and four types of testicular cells, including Sertoli, Leydig, spermatogonial and spermatocyte cells. The results showed that YCl3 exposure causes substantial damage to mouse testes and induces apoptosis and autophagy, but not pyroptosis or necrosis, in testicular cells. Genome-wide gene expression analysis revealed that YCl3 induced significant changes in gene expression, with Ca2+ and mitochondria-related genes being the most significantly altered. Mechanistically, YCl3 exposure induced mitochondrial dysfunction in testicular cells, triggering the overproduction of reactive oxygen species (ROS) by impairing the Nrf2 pathway, regulating downstream Ho-1 target protein expression, and increasing Ca2+ levels to activate the CamkII/Ampk signaling pathway. Blocking ROS production or Ca2+ signaling significantly attenuates apoptosis and autophagy, while supplementation with Ca2+ reverses the suppression of apoptosis and autophagy by ROS blockade in testicular cells. Notably, apoptosis and autophagy induced by YCl3 treatment are independent of each other. Thus, our study suggests that YCl3 may impair the antioxidant stress signaling pathway and activate the calcium pathway through the ROS-Ca2+ axis, which promotes testicular cell apoptosis and autophagy independently, thus inducing testicular damage and impairing male reproductive function.

High-frequency rTMS over the left DLPFC improves the response inhibition control of young healthy participants: an ERP combined 1H-MRS study.

Introduction: Unlike the effect of repetitive transcranial magnetic stimulation (rTMS) in treating neuropsychiatric diseases, little is known about how personal factors might account for the disparity of results from studies of cognition and rTMS. In this study, we investigated the effects of high-frequency rTMS on response inhibition control and explored the time course changes in cognitive processing and brain metabolic mechanisms after rTMS using event-related potentials (ERPs) and magnetic resonance spectroscopy (1H-MRS). Methods: Participants were all right-handed and were naive to rTMS and the Go/NoGo task. Twenty-five healthy young participants underwent one 10 Hz rTMS session per day in which stimulation was applied over the left dorsolateral prefrontal cortex (DLPFC), and a homogeneous participant group of 25 individuals received a sham rTMS treatment for 1 week. A Go/NoGo task was performed, an electroencephalogram (EEG) was recorded, and 1H-MRS was performed. Results: The results revealed that there was a strong trend of decreasing commission errors of NoGo stimuli by high frequency rTMS over the left DLPFC, whereas there was no significant difference between before and after rTMS treatment with respect to these parameters in the sham rTMS group. High-frequency rTMS significantly increased the amplitude of NoGo-N2 but not Go-N2, Go-P3, or NoGo-P3. The myo-inositol /creatine complex (MI/Cr) ratio, indexing cerebral metabolism, in the left DLPFC was decreased in the rTMS treated group. Discussion: This observation supports the view that high-frequency rTMS over the left DLPFC has the strong tendency of reducing commission errors behaviorally, increase the amplitude of NoGo-N2 and improve the response inhibition control of healthy young participants. The results are consistent with the excitatory properties of high frequency rTMS. We suggest that the increase in the NoGo-N2 amplitude may be related to the increased excitability of the DLPFC-anterior cingulate cortex (ACC) neural loop. Metabolic changes in the DLPFC may be a possible mechanism for the improvement of the response inhibition control of rTMS.

Regulation of proliferation and apoptosis of aging periodontal ligament cells by autophagy-related gene 7.

BACKGROUND: Human periodontal ligament cells (hPDLCs) can be applied in periodontal regeneration engineering to repair the tissue defects related to periodontitis. Theoretically, it can affect the vitality of hPDLCs that cell aging increases apoptosis and decreases autophagy. Autophagy is a highly conserved degradation mechanism, which degrades the aging and damaged intracellular organelles through autophagy lysosomes to maintain normal intracellular homeostasis. Meanwhile, autophagy-related gene 7 (ATG7) is a key gene that regulates the level of cellular autophagy. OBJECTIVE: This study was to explore the effects of autophagic regulation of aging hPDLCs on cell proliferation and cell apoptosis. METHODS: A cell model of aging hPDLCs overexpressing and silencing ATG7 were respectively constructed by lentiviral vectors in vitro. A series of experiments was performed to confirm relevant senescence phenotype on aging hPDLCs, and to detect the effects of changes in autophagy on their proliferation and apoptosis-related factors in aging hPDLCs. RESULTS: The results showed that overexpression of ATG7 could motivate autophagy, promoting proliferation of aging hPDLCs and inhibiting apoptosis synchronously (P < 0.05). On the contrary, suppressing autophagy levels by silencing ATG7 would inhibit cell proliferation and accelerate cell senescence (P < 0.05). CONCLUSION: ATG7 regulates the proliferation and apoptosis of aging hPDLCs. Hence, autophagy may act as a target to delay senescence of hPDLCs, which can be helpful in the future in-depth study on regeneration and functionalization of periodontal supporting tissues.

Correlation Between the Peripheral Neuropathy and Levels of hs-CRP, IL-1ß and IL-6 in Senile Parkinson's Disease Patients.

This study was carried out to investigate the correlation between the onset of peripheral neuropathy and levels of hypersensitive C-reactive protein (hs-CRP), interleukin 1ß (IL-1ß) and IL-6 in senile Parkinson's disease (PD) patients. For this purpose, a total of 60 PD patients and 60 age-matched healthy subjects were enrolled in this study and received the assessment for peripheral nerves by using the quantified method. Besides, levels of hs-CRP, IL-1ß and IL-6 in serum were determined to analyze the correlation between the clinical features, including the severity of PD and cognitive decline, and the levels of hs-CRP, IL-1ß and IL-6. Results showed that PD patients had more cases of peripheral neuropathy than those in the healthy control group. Levels of hs-CRP, IL-1ß and IL-6 in the serum of PD patients were much higher than those in the healthy control (P<0.05). Besides, PD patients had lower scores of MMSE and MoCA but higher CNPI scores when compared to the healthy control group. As a result, we found that the severity of peripheral neuropathy was in a positive correlation with the levels of hs-CRP, IL-1ß and IL-6. It was concluded that PD patients generally have peripheral neuropathy that may correlate with the increases in the levels of hs-CRP, IL-1ß and IL-6, and early intervention may mitigate the development and progression of peripheral neuropathy.