Search

Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

The aims of this retrospective study were to evaluate the clinical applicability of the latest International Society for the Study of Vulvovaginal Disease (ISSVD) and International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology for vulvar diseases, and to explore a new evaluation flow to optimize decision-making on diagnosis. A total of 1,068 patients with 5,340 qualified vulvar images were evaluated by observers using 2011 ISSVD and 2011 IFCPC terminology systems. The sensitivity, specificity, positive predictive value, negative predictive value, Youden Index and Overall Diagnostic Value (ODV) were calculated for each finding in the two systems. Then the disease diagnosis order and a diagnosis flow draft (DFD) were obtained. A total of 15 kinds of vulvar diseases were diagnosed. The proportion of patients accompanied with cervical or vaginal intraepithelial neoplasia was highest (83.3 %) in vulvar Paget's disease group (p<0.001). Total area of lesions was larger in vulvar Paget's disease, lichen simplex chronicus and lichen sclerosus group (p<0.001). Among the top five findings of ODV, some findings inferred several (≥6) kinds of diseases, while some findings only exist in a certain disease. When the DFD was used, the agreement between the initial impression and histopathology diagnosis was 68.8 %, higher than those when ISSVD an IFCPC terminology systems used (p=0.028), and it didn't change with the experience of the observer (p=0.178). Based on the findings in ISSVD and IFCPC terminology systems, we explored a DFD for observers with different experience on the detection of vulvar disease. [ABSTRACT FROM AUTHOR]

This study aims to characterize the genetic variability of HPV58, identify novel lineages and sublineages, and explore the association between persistent/multiple HPV58 infections and genetic variation. In this study, samples from 124 women with HPV58 infection in Eastern China were collected and 81 isolates of E6 and L1 full‐length genes were successfully amplified from 55 samples. We evaluated the diversity of genetic variants and performed correlation analyses between genetic variability and pathology, vaccination, multiple infections, and persistent infections. Among the E6 and L1 gene sequences collected, the dominant prevailing sublineages were A1 (46.2%) and A2 (23.1%). In addition, we found two potential novel sublineages denoted as the A4 and A5 sublineage. A total of 50 nucleotide substitutions, including 28 synonymous substitutions and 22 nonsynonymous substitutions, were observed in the E6 and L1 genes. Among them, variants with A388C/K93N substitutions in the E6 gene correlated with persistent infection (≥1 and ≥2 years) (p < 0.005), and C307T/C66C was associated with persistent infection (≥2 years) (p < 0.005). Notably, two mutations above were detected in the isolate from the patient with breakthrough vaccine infection. Our study found two novel sublineages and sites of genetic variability in multiple and persistent infection variants. In addition, we identified two mutational sites associated with persistent infection. This study provides new insight into the clinical characteristics of HPV 58 genetic variations and offers new ideas for research on next‐generation vaccines in Eastern China. [ABSTRACT FROM AUTHOR]

Pyroptosis is a type of programmed cell death, displaying caspase‐1‐dependent and pro‐inflammatory features. Purinergic 2X4 (P2X4) receptor activation in response to high‐adenosine triphosphate release can induce inflammation. Envelope glycoprotein 120 (gp120) of human immunodeficiency virus type 1 is considered one of the primary pathogens leading to neuronal injury. In this study, we investigated the possible role of P2X4 receptor activation in gp120‐triggered pyroptosis in cultured satellite glial cells (SGCs) of rat dorsal root ganglia (DRG). MTS assay, TdT‐mediated dUTP Nick‐end labeling assay, real‐time RT‐PCR, and western blotting et al. methods were used. The results indicated that the expression of P2X4 receptor in SGCs of DRG was up‐regulated upon cultured with gp120 for 24 h. The highest decrease in viability of SGCs due to gp120 treatment was accompanied by marked increases of positive pyroptosis cells and cellular lactate dehydrogenase release, elevated levels of interleukin‐1β, interleukin‐18, active caspase‐1 and NOD‐like receptor family, pyrin domain containing 1, and enhanced phosphorylation of p38MAPK. These abnormal changes because of gp120 were significantly inhibited and cell viability was markedly improved when SGCs of DRG were treated with short hairpin RNAs targeting P2X4 receptor. Our data suggest that silencing of P2X4 receptor may act effectively against gp120‐induced pyroptosis mediated by the activation of NOD‐like receptor family, pyrin domain containing 1 inflammasome and caspase‐1 signaling in SGCs of DRG. [ABSTRACT FROM AUTHOR]

The upregulation of nociceptive ion channels expressed in dorsal root ganglia (DRG) contributes to the development and retaining of diabetic pain symptoms. The flavonoid quercetin (3,3′,4′,5,7‐pentahydroxyflavone) is a component extracted from various fruits and vegetables and exerts anti‐inflammatory, analgesic, anticarcinogenic, antiulcer, and antihypertensive effects. However, the exact mechanism underlying quercetin's analgesic action remains poorly understood. The aim of this study was to investigate the effects of quercetin on diabetic neuropathic pain related to the P2X4 receptor in the DRG of type 2 diabetic rat model. Our data showed that both mechanical withdrawal threshold and thermal withdrawal latency in diabetic rats treated with quercetin were higher compared with those in untreated diabetic rats. The expression levels of P2X4 messenger RNA and protein in the DRG of diabetic rats were increased compared with the control rats, while quercetin treatment significantly inhibited such enhanced P2X4 expression in diabetic rats. The satellite glial cells (SGCs) enwrap the neuronal soma in the DRG. Quercetin treatment also lowered the elevated coexpression of P2X4 and glial fibrillary acidic protein (a marker of SGCs) and decreased the upregulation of phosphorylated p38 mitogen‐activated protein kinase (p38MAPK) in the DRG of diabetic rats. Quercetin significantly reduced the P2X4 agonist adenosine triphosphate‐activated currents in HEK293 cells transfected with P2X4 receptors. Thus, our data demonstrate that quercetin may decrease the upregulation of the P2X4 receptor in DRG SGCs, and consequently inhibit P2X4 receptor‐mediated p38MAPK activation to relieve the mechanical and thermal hyperalgesia in diabetic rats. The expression levels of P2X4 receptor in the dorsal root ganglia (DRG) satellite glial cells (SGCs) of diabetic rats were increased to relate to hyperalgesia. Quercetin decreased the upregulation of the P2X4 receptor in DRG SGCs. Consequently, quercetin relieved the mechanical and thermal hyperalgesia in diabetic rats. [ABSTRACT FROM AUTHOR]

Superior cervical ganglia (SCG) innervate the myocardium and participate in sympathoexcitatory transmission. P2Y12 receptor is expressed in satellite glial cells (SGCs). This study seeks to clarify whether the P2Y12 receptor is involved in the sympathoexcitation reflex after myocardial ischemia (MI). MI model was induced by occlusion of the left coronary artery. P2Y12 were assayed by real time PCR and Western blotting. Our results showed that expression levels of P2Y12 mRNA and protein were significantly higher in the MI group than in the sham group. Administration of P2Y12 short hairpin RNA (shRNA) caused downregulation of the P2Y12 receptor in the SCG. In MI rats plus P2Y12 shRNA treatment group, the abnormal changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), electrocardiograms (ECGs), and cardiac tissue structures were alleviated. When the treatment of P2Y12shRNA in MI rats, upregulated coexpression values of P2Y12 and glial fibrillary acidic protein (GFAP), the upregulation of tumor necrosis factor α (TNF-α) and phosphorylated P38 mitogen activated protein kinase (p-P38 MAPK) in the SCG were decreased. Downregulation of the P2Y12 receptor in the SCG after MI may improve cardiac function by alleviating the sympathoexcitatory reflex. [ABSTRACT FROM AUTHOR]

HIV-1 envelope glycoprotein (Glycoprotein 120, gp120) can directly stimulate primary sensory afferent neurons and cause chronic neuropathic pain. The P2X 3 receptor in the dorsal root ganglia (DRG) is associated with the transmission of neuropathic pain. Curcumin isolated from the herb Curcuma rhizome has anti-inflammatory and anti-tumor effects. The water solubility, targeting and bioavailability of curcumin can be improved by nanoparticle encapsulation. In this study, we sought to explore the effects of nanoparticle-encapsulated curcumin (nano curcumin) on HIV-gp120-induced neuropathic pain mediated by the P2X 3 receptor in DRG neurons. The results showed that mechanical and thermal hyperalgesia in rats treated with gp120 were increased compared to those in the control group. The expression levels of P2X 3 mRNA and protein in rats treated with gp120 were higher than those in the control group. Nano curcumin treatment decreased mechanical hyperalgesia and thermal hyperalgesia and upregulated the expression levels of P2X 3 mRNA and protein in rats treated with gp120. Nano curcumin treatment also reduced the ERK1/2 phosphorylation levels in gp120-treated rat DRG. In addition, P2X 3 agonist α,β-methylene ATP (α,β-meATP)-induced currents in DRG neurons cultured with gp120 significantly decreased after co-treatment with nano curcumin. Therefore, nano curcumin treatment may inhibit P2X 3 activation, decrease the sensitizing DRG primary afferents and relieve mechanical hyperalgesia and thermal hyperalgesia in gp120-treated rats. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a type of chronic pain caused by nervous system damage and dysfunction. The pathogenesis of chronic pain is complicated, and there are no effective therapies for neuropathic pain. Studies show that the P2X 4 receptor expressed in the satellite glial cells (SGCs) of dorsal root ganglia (DRG) is related to neuropathic pain. Artemisinin is a monomeric component extracted from traditional Chinese medicine and has a variety of important pharmacological effects and potential applications. This study observed the effect of artemisinin on neuropathic pain and delineated its possible mechanism. The chronic constriction injury (CCI) rat model was used in this study. The results demonstrated that artemisinin relieved pain behaviors in the CCI rats, inhibited the expression of P2X 4 receptor in the DRG, and decreased the ATP-activated currents in HEK293 cells transfected with P2X 4 plasmid. Dual-labeling immunofluorescence showed that the coexpression of P2X 4 receptor and glial fibrillary acidic protein (GFAP) in the DRG of CCI rats was increased compared to control rats. After CCI rats were treated with artemisinin, the coexpression of P2X 4 receptor and GFAP in the DRG was significantly decreased compared to the CCI group. This finding suggested that artemisinin could inhibit the nociceptive transmission mediated by P2X 4 receptor in the DRG SGCs and thus relieve pain behaviors in the CCI rats. [ABSTRACT FROM AUTHOR]

Purpose: To identify the bibliometric information of Human papillomavirus (HPV) genotype co-infection in certain literature database over the past two decades., Methods: Web of Science was used as the main database to identify all eligible articles focusing on HPV genotype co-infection at the date of October 16, 2022. From this journal database, we identified 463 articles on HPV genotype co-infection, conducted statistical analysis according to the author, journal, publication year and month, country or region, keyword and impact factor., Results: The articles included in our analysis were published between 1994 and 2022. The index of citations per year ranged from 170.4 to 13.1. These articles were from 78 countries or regions, with most publications from the United States (n = 73), followed by China (n = 65) and Italy (n = 50). The journal that contributed the most publications on HPV heterotypic gene co-infection was PLOS ONE with a total of 29 articles, followed by JOURNAL OF MEDICAL VIROLOGY (n = 28), INFECTIOUS AGENTS AND CANCER (n = 14) and JOURNAL OF CLINICAL VIROLOGY (n = 12). Among existing research in the field of HPV co-infection, we found that epidemiological distribution and infection mechanism has been the two major topics for scholars, and studies on detection methods for HPV multiple genotypes were also included., Conclusion: Over decades, epidemiological studies and mechanism investigationhas been the central topics when it comes to HPV genotypes co-infection. Studies on HPV co-infection remained relatively insufficient, mainly stays in qualitative level while detailed infection data and high quality literature publications were still lack of valuable discussion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bi, Gong, Mo, Wang, Qu, Wang, Shi, Zhang, Sui and Li.)

Objective: This study aimed to verify the role of basic fibroblast growth factor (bFGF)-bone mesenchymal stem cells (BMSCs) loaded on collagen scaffolds for the repair of injured endometrium., Methods: We established an intrauterine adhesion (IUA) model in rats by endometrial resection and implanted BMSCs and bFGF-BMSCs loaded on collagen scaffolds into uteri. A total of 100 IUA model rats were divided into five groups: the control group, scaffold group, BMSC+scaffold group, vector-BMSC group, and bFGF-BMSC+scaffold group. The rats were sacrificed on the 3 rd , 7 th , 15 th , and 45 th days. The endometrium thickness, number of glands, and microvascular density were measured by hematoxylin and eosin staining, Masson staining, and immunohistochemistry staining of CD31. The expression of bFGF, vascular endothelial growth factor (VEGF), vimentin, and Ki67 was assayed by immunohistochemistry staining., Results: The bFGF-BMSCs loaded on the collagen scaffold significantly increased the endometrial thickness, gland number, and microvascular density, which greatly promoted the regeneration of the injured endometrium (P<0.0001). In addition, the expression levels of bFGF, VEGF, vimentin, and Ki67 were significantly higher in the bFGF-BMSC+scaffold group than in the BMSC+scaffold group (P<0.05)., Conclusions: Our findings indicated that bFGF-BMSCs loaded on collagen scaffolds have the ability to prompt the regeneration of the endometrium after injury, contributing to a better understanding of stem cell treatment for intrauterine adhesion., Competing Interests: None., (AJTR Copyright © 2022.)

The upregulation of nociceptive ion channels expressed in dorsal root ganglia (DRG) contributes to the development and retaining of diabetic pain symptoms. The flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) is a component extracted from various fruits and vegetables and exerts anti-inflammatory, analgesic, anticarcinogenic, antiulcer, and antihypertensive effects. However, the exact mechanism underlying quercetin's analgesic action remains poorly understood. The aim of this study was to investigate the effects of quercetin on diabetic neuropathic pain related to the P2X 4 receptor in the DRG of type 2 diabetic rat model. Our data showed that both mechanical withdrawal threshold and thermal withdrawal latency in diabetic rats treated with quercetin were higher compared with those in untreated diabetic rats. The expression levels of P2X 4 messenger RNA and protein in the DRG of diabetic rats were increased compared with the control rats, while quercetin treatment significantly inhibited such enhanced P2X 4 expression in diabetic rats. The satellite glial cells (SGCs) enwrap the neuronal soma in the DRG. Quercetin treatment also lowered the elevated coexpression of P2X 4 and glial fibrillary acidic protein (a marker of SGCs) and decreased the upregulation of phosphorylated p38 mitogen-activated protein kinase (p38MAPK) in the DRG of diabetic rats. Quercetin significantly reduced the P2X 4 agonist adenosine triphosphate-activated currents in HEK293 cells transfected with P2X 4 receptors. Thus, our data demonstrate that quercetin may decrease the upregulation of the P2X 4 receptor in DRG SGCs, and consequently inhibit P2X 4 receptor-mediated p38MAPK activation to relieve the mechanical and thermal hyperalgesia in diabetic rats., (© 2018 Wiley Periodicals, Inc.)

Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of osthole on diabetic neuropathic pain (DNP) involving the P2X 4 receptor on satellite glial cells (SGCs) in the dorsal root ganglia (DRG) of type 2 diabetic rats. These data showed that the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in DM rats were lower than those in control rats. MWT and TWL in DM rats treated with osthole were higher compared with those in untreated DM rats. The expression levels of P2X 4 mRNA and protein in the DRG of DM rats were higher compared with those in the control rats, while those in DM rats treated with osthole were significantly lower compared with those in the untreated DM rats. Osthole treatment decreased the co-expression levels of P2X 4 and glial fibrillary acidic protein (GFAP) and reduced the up-regulated expression of interleukin-1 beta (IL-1β), tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and phosphorylated-p38MAPK and enhanced the down-regulation of IL-10 in DM rats. Thus, osthole treatment may act on the P2X 4 receptor to alleviate the mechanical and thermal hyperalgesia in DM rats., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Insulin resistance and type 2 diabetes mellitus (T2DM) are highly prevalent around the world. Elevated concentrations of free fatty acids (FFAs) are closely related to insulin resistance and T2DM. P2X 7 receptor is an ion channel gated by ATP, which is implicated in various scenarios including immune response, pain, and inflammation. In this study, we have explored whether P2X 7 receptor is involved in pathological changes in human umbilical vein endothelial cells (HUVECs) induced by high FFA treatment, and the potential beneficial effects of evodiamine. Evodiamine could effectively suppress the enhanced expression of P2X 7 receptor caused by high FFAs at both mRNA and protein levels. In addition, high FFA-induced cytotoxicity, the upregulated release of ATP, and production of reactive oxygen species (ROS) could be ameliorated by evodiamine in HUVECs. Evodiamine could also reverse the decreased NO formation and the increased adhesive events of immune cells at high FFAs. Moreover, evodiamine inhibited P2X 7 -dependent TNF- α expression and ERK 1/2 phosphorylation due to high FFAs. All these results indicated that evodiamine could correct the upregulated expression of P2X 7 receptor induced under high FFA condition in HUVECs, and consequently suppressed oxidative stress and inflammatory responses.

Superior cervical ganglia (SCG) innervate the myocardium and participate in sympathoexcitatory transmission. P2Y 12 receptor is expressed in satellite glial cells (SGCs). This study seeks to clarify whether the P2Y 12 receptor is involved in the sympathoexcitation reflex after myocardial ischemia (MI). MI model was induced by occlusion of the left coronary artery. P2Y 12 were assayed by real time PCR and Western blotting. Our results showed that expression levels of P2Y 12 mRNA and protein were significantly higher in the MI group than in the sham group. Administration of P2Y 12 short hairpin RNA (shRNA) caused downregulation of the P2Y 12 receptor in the SCG. In MI rats plus P2Y 12 shRNA treatment group, the abnormal changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), electrocardiograms (ECGs), and cardiac tissue structures were alleviated. When the treatment of P2Y 12 shRNA in MI rats, upregulated co-expression values of P2Y 12 and glial fibrillary acidic protein (GFAP), the upregulation of tumor necrosis factor α (TNF-α) and phosphorylated P38 mitogen activated protein kinase (p-P38 MAPK) in the SCG were decreased. Downregulation of the P2Y 12 receptor in the SCG after MI may improve cardiac function by alleviating the sympathoexcitatory reflex., (© 2017 Wiley Periodicals, Inc.)