Advances in cell membrane-based biomimetic nanodelivery systems for natural products.

Active components of natural products, which include paclitaxel, curcumin, gambogic acid, resveratrol, triptolide and celastrol, have promising anti-inflammatory, antitumor, anti-oxidant, and other pharmacological activities. However, their clinical application is limited due to low solubility, instability, low bioavailability, rapid metabolism, short half-life, and strong off-target toxicity. To overcome these drawbacks, cell membrane-based biomimetic nanosystems have emerged that avoid clearance by the immune system, enhance targeting, and prolong drug circulation, while also improving drug solubility and bioavailability, enhancing drug efficacy, and reducing side effects. This review summarizes recent advances in the preparation and coating of cell membrane-coated biomimetic nanosystems and in their applications to disease for targeted natural products delivery. Current challenges, limitations, and prospects in this field are also discussed, providing a research basis for the development of multifunctional biomimetic nanosystems for natural products.

[Charcoal-frying process and quality markers of Sanguisorbae Radix based on hemostatic effect].

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

Effect of Intraorbital Mechanical Compression on Retinal Microvascular Perfusion in Quiescent Thyroid-Associated Ophthalmopathy Based on Ocular Biomechanics Measured by Corvis ST.

INTRODUCTION: To analyze the correlation between orbital compliance and retinal vessel density (VD) based on dynamic Scheimpflug analyzer (Corvis ST) and optical coherence tomographic angiography (OCT-A). METHODS: In this prospective observational study, 65 eyes of 44 patients with thyroid-associated ophthalmopathy (TAO) in quiescent stage were included (15 males and 29 females). The whole eye movement (WEM) was detected by Corvis ST. The superficial capillary plexus VD (SCP-VD) and deep capillary plexus VD (DCP-VD) were obtained by scanning the 3 × 3 mm area around the fovea using OCT-A, while the peripapillary vessel density (ppVD) was obtained by scanning the 4.5 × 4.5 mm area around the optic disk. Covariances including biomechanically corrected intraocular pressure (bIOP), axial length, age and gender were adjusted during data analysis. RESULTS: The mean WEM of the participants was 0.235 ± 0.066 mm. The mean SCP-VD and DCP-VD in whole image were 46.20% ± 3.77% and 50.51% ± 3.96%; the mean whole pp-VD was 49.75% ± 2.01%. WEM was positively correlated with SCP-VD (r = 0.327, p = 0.01) and the whole pp-VD (r = 0.394, p < 0.01) after adjusting by gender, axial length (AL), age and bIOP, but it was not significantly correlated with DCP-VD (r = 0.072 p = 0.581). CONCLUSION: Increase in orbital pressure might reduce retinal microvascular perfusion. Our data suggest orbital mechanical compression may be an important cause of retinal VD changes in quiescent patients with TAO.

Sono-assembly of ellagic acid into nanostructures significantly enhances aqueous solubility and bioavailability.

INTRODUCTION: Ellagic acid (EA), commonly found in foods, offers significant health benefits in combating chronic diseases. However, its therapeutic potential is hindered by its extremely poor solubility and bioavailability. METHOD: In this study, EA nanoparticles (EA NPs) were produced using a sono-assembly method, without additional agents. RESULTS: EA NPs exhibited stick-like nanoparticle structures with an average size of 147.3 ± 0.73 nm. EA NPs likely adopt a tunnel-type solvate structure, with 4 water participating in disruption of intramolecular hydrogen bonds in EA and establishment of intermolecular hydrogen bonds between EAs. Importantly, EA NPs exhibited remarkable enhancements in water solubility, with 120.7-fold increase in water, and 97.8-fold increase in pH 6.8 buffer. Moreover, ex vivo intestinal permeability studies demonstrated significant improvements (P < 0.5). These findings were further supported by in vivo pharmacokinetic studies, where EA NPs significantly enhanced the relative bioavailability of EA by 4.69 times.

Tissue-specific transcriptome and metabolome analyses reveal candidate genes for lignan biosynthesis in the medicinal plant Schisandra sphenanthera.

Schisandra sphenanthera is an extremely important medicinal plant, and its main medicinal component is bioactive lignans. The S. sphenanthera fruit is preferred by the majority of consumers, and the root, stem, and leaf are not fully used. To better understand the lignan metabolic pathway, transcriptome and metabolome analyses were performed on the four major tissues of S. sphenanthera. A total of 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the root had the highest abundance of unique unigenes (9703), and the leaves had the lowest (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of processes involved in lignan metabolism. In different tissues, lignans were preferentially enriched in fruit and roots by gene expression profiles related to lignan metabolism and relative lignan compound content. Furthermore, schisandrin B is an important compound in S. sphenanthera. According to weighted gene co-expression network analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB18, bHLH3, and bHLH5 can be related to the accumulation of lignans in S. sphenanthera fruit, CCR5, SDH4, CYP8, CYP20, and ERF7 can be related to the accumulation of lignans in S. sphenanthera roots. In this study, transcriptome sequencing and targeted metabolic analysis of lignans will lay a foundation for the further study of their biosynthetic genes.

Construction and application of artificial lipoproteins using adiposomes.

Lipoproteins are complex particles comprised of a neutral lipid core wrapped with a phospholipid monolayer membrane and apolipoproteins on the membrane, which is closely associated with metabolic diseases. To facilitate the elucidation of its formation and dynamics, as well as its applications, we developed an in vitro system in which adiposomes, consisting of a hydrophobic core encircled by a monolayer-phospholipid membrane, were engineered into artificial lipoproteins (ALPs) by recruiting one or more kinds of apolipoproteins, for example, apolipoprotein (Apo) A-I, ApoE, ApoA-IV, and ApoB. In vitro and in vivo studies demonstrated the stability and biological activity of ALPs derived from adiposomes, which resembles native lipoproteins. Of note, adiposomes bearing ApoE were internalized via clathrin-mediated endocytosis following LDLR binding and were delivered to lysosomes. On the other hand, adiposomes bearing ApoA-IV mimicked the existing form of endogenous ApoA-IV and exhibited significant improvement in glucose tolerance in mice. In addition, the construction process was simple, precise, reproducible, as well as easy to adjust for mass production. With this experimental system, different apolipoproteins can be recruited to build ALPs for some biological goals and potential applications in biomedicine.

New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.

Over the past thirty years, the importance of chemokines and their seven-transmembrane G protein-coupled receptors (GPCRs) has been increasingly recognized. Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes, including host homeostasis and responses to disease. Genetic and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional heterogeneity. Imbalances and defects in the system contribute to the pathogenesis of a variety of diseases, including cancer, immune and inflammatory diseases, and metabolic and neurological disorders, which render the system a focus of studies aiming to discover therapies and important biomarkers. The integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states, including, among others, coronavirus disease 2019 (COVID-19). In this review, by reporting the latest advances in chemokine biology and results from analyses of a plethora of sequencing-based datasets, we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network, focusing on chemokine-mediated inflammation and cancer. Clarification of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.

Functional insight into Cordyceps militaris sugar transporters by structure modeling, network analysis and allosteric regulation.

Insights into the structures, functions and dynamics of Cordyceps militaris (C. militaris) sugar transporters are necessary for understanding their versatile metabolic capability for fungal growth. The sequence-function relationship study of 85 C. militaris sugar transporters showed that there is a gap between phylogenetic-based subfamily classification and their functions. Beyond protein sequences, structural modeling and principal component analysis of the structural ensemble revealed the different folds of the Car and Org subfamilies. Performing channel detection and network analysis found that the Alp and Hex subfamilies can be specifically distinguished from others by the betweenness of channel residues. Signature dynamics analysis further suggested that the Hex subfamily demonstrates different dynamics, with high flexibility at the H1 region in TM11. Furthermore, the H1 region as an allosteric site was examined by network parameter calculations that guided allosteric pathways between this region and the channel cavity. Together with gene expression data of C. militaris, e.g., Hex06741 in the Hex subfamily, it was promisingly expressed when sugar utilization was altered. This work demonstrates an in silico framework for investigating C. militaris sugar transporters as an example case study of the allosteric activity of the Hex subfamily and can facilitate sugar transporter engineering design that can further optimize the preferable sugar utilization and fermentation process of C. militaris.

HNRNPA2B1 as a potential therapeutic target for thymic epithelial tumor recurrence: An integrative network analysis.

Thymic epithelial tumors (TETs) are rare malignant tumors, and the molecular mechanisms of both primary and recurrent TETs are poorly understood. Here we established comprehensive proteomic signatures of 15 tumors (5 recurrent and 10 non-recurrent) and 15 pair wised tumor adjacent normal tissues. We then proposed an integrative network approach for studying the proteomics data by constructing protein-protein interaction networks based on differentially expressed proteins and a machine learning-based score, followed by network modular analysis, functional enrichment annotation and shortest path inference analysis. Network modular analysis revealed that primary and recurrent TETs shared certain common molecular mechanisms, including a spliceosome module consisting of RNA splicing and RNA processing, but the recurrent TET was specifically related to the ribosome pathway. Applying the shortest path inference to the collected seed gene module identified that the ribonucleoprotein hnRNPA2B1 probably serves as a potential target for recurrent TET therapy. The drug repositioning combined molecular dynamics simulations suggested that the compound ergotamine could potentially act as a repurposing drug to treat recurrent TETs by targeting hnRNPA2B1. Our study demonstrates the value of integrative network analysis to understand proteotype robustness and its relationships with genotype, and provides hits for further research on cancer therapeutics.

Effectiveness of parent-training program on children with autism spectrum disorder in China.

Objective: This study intends to explore the effect of parent-training program on the rehabilitation intervention in children with autism spectrum disorder (ASD) in Chinese-speaking areas of China by offering parent skill training and psychology counseling. Methods: From January 2018 to June 2019, a total of 80 children diagnosed with ASD from the Department of Children Healthcare of Wuxi Children's Hospital were randomly grouped into the parent training groups and control groups. Parents in the training group received 12 weeks of skill training, including 8 group and 2 individual training sessions, as well as psychology counseling. This enabled them to give their children >2 h of intervention training daily in a natural environment. Children in the control group were placed on a rehabilitation waiting list or received general community training. Before grouping and after the intervention, all children underwent neuropsychological evaluations with Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Gesell Developmental Schedule (GDS). GDS covers five sectors, namely adaptive behavior, gross motor, fine motor, language, and personal-social behavior. Results: Statistically significant differences were not detected between the two groups in ABC, CARS, and GDS scoring at baseline evaluation. And significant differences were detected between the two groups in ABC, CARS, adaptive behavior, and personal-social behavior scoring at endpoint evaluation. Furthermore, the re-evaluation results of ABC scoring and CARS scoring of the children in the parent training group decreased significantly from the preliminary evaluation results when compared before and after the intervention. Moreover, the intragroup comparison of adaptive behavior scoring, language scoring, and personal-social behavior scoring of the experiment group increased significantly from the preliminary evaluation results, while the difference of the same of the children in the control group between re-evaluation and preliminary evaluation did not differ significantly. Conclusions: In China, the parent-training program enables parents to train ASD children in a natural environment, which would markedly improve behavioral problems, core symptoms, adaptability, language competence, and social development capability.

Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation.

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone mineralization and is highly variable in its clinical phenotype. The disease occurs due to various loss-of-function mutations in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). In this work, a data-driven and biophysics-based approach is proposed for the large-scale analysis of ALPL mutations-from nonpathogenic to severe HPPs. By using a pipeline of synergistic approaches including sequence-structure analysis, network modeling, elastic network models and atomistic simulations, we characterized allosteric signatures and effects of the ALPL mutations on protein dynamics and function. Statistical analysis of molecular features computed for the ALPL mutations showed a significant difference between the control, mild and severe HPP phenotypes. Molecular dynamics simulations coupled with protein structure network analysis were employed to analyze the effect of single-residue variation on conformational dynamics of TNSALP dimers, and the developed machine learning model suggested that the topological network parameters could serve as a robust indicator of severe mutations. The results indicated that the severity of disease-associated mutations is often linked with mutation-induced modulation of allosteric communications in the protein. This study suggested that ALPL mutations associated with mild and more severe HPPs can exert markedly distinct effects on the protein stability and long-range network communications. By linking the disease phenotypes with dynamic and allosteric molecular signatures, the proposed integrative computational approach enabled to characterize and quantify the allosteric effects of ALPL mutations and role of allostery in the pathogenesis of HPPs.

Altered Metabolic Characteristics in Plasma of Young Boys with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder with no clinical biomarker. This study used untargeted metabolomic analysis to identify metabolic characteristics in plasma that can distinguish ASD children. 29 boys with ASD (3.02 ± 0.67 years) and 30 typically developing (TD) boys (3.13 ± 0.46 years) were recruited. Developmental and behavioral assessments were conducted in ASD group. Samples of plasma were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between metabolite concentration and scale score was assessed by Spearman rank correlation. Altered metabolic characteristics were found in boys with ASD. In Receiver Operating Characteristic (ROC) analysis, ornithine had the highest AUC (Area under ROC) value. Furthermore, the concentration of choline and ornithine was negatively correlated with ABC-language score in ASD group.

Insights into Conformational Dynamics and Allostery in DNMT1-H3Ub/USP7 Interactions.

DNA methyltransferases (DNMTs) including DNMT1 are a conserved family of cytosine methylases that play crucial roles in epigenetic regulation. The versatile functions of DNMT1 rely on allosteric networks between its different interacting partners, emerging as novel therapeutic targets. In this work, based on the modeling structures of DNMT1-ubiquitylated H3 (H3Ub)/ubiquitin specific peptidase 7 (USP7) complexes, we have used a combination of elastic network models, molecular dynamics simulations, structural residue perturbation, network modeling, and pocket pathway analysis to examine their molecular mechanisms of allosteric regulation. The comparative intrinsic and conformational dynamics analysis of three DNMT1 systems has highlighted the pivotal role of the RFTS domain as the dynamics hub in both intra- and inter-molecular interactions. The site perturbation and network modeling approaches have revealed the different and more complex allosteric interaction landscape in both DNMT1 complexes, involving the events caused by mutational hotspots and post-translation modification sites through protein-protein interactions (PPIs). Furthermore, communication pathway analysis and pocket detection have provided new mechanistic insights into molecular mechanisms underlying quaternary structures of DNMT1 complexes, suggesting potential targeting pockets for PPI-based allosteric drug design.

Antioxidant and Antidiabetic Activity of Proanthocyanidins from Fagopyrum dibotrys.

Proanthocyanidins are natural glycosidase inhibitors with excellent antioxidant activity. This study aims to search for a new source of proanthocyanidins for the prevention and treatment of type 2 diabetes with higher content and better activity and get their structure elucidated. First, the total proanthocyanidins contents (TOPCs), antioxidant activity, antidiabetic activity of seven common Polygonaceae plants were analyzed and compared. Then proanthocyanidins from the rhizome of Fagopyrum dibotrys were purified, and the detailed structure was comprehensively analyzed by ultraviolet visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), 13C nuclear magnetic resonance spectroscopy (13C NMR), reversed-phase high-performance liquid chromatography-electrospray mass spectrometry (RP-HPLC-ESI-MS), and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The rhizome of F. dibotrys showed the highest TOPCs, the strongest antioxidant, and antidiabetic activities; the TOPCs, antioxidant and antidiabetic activities were all very significantly positively correlated. Proanthocyanidins purified from the rhizome of F. dibotrys showed better antidiabetic activity than grape seed proanthocyanidins (GsPs). Seventy-two proanthocyanidins from trimer to undecamer with a mean degree of polymerization (mDP) of about 5.02 ± 0.21 were identified with catechin and epicatechin as the dominant monomers. Conclusion: Proanthocyanidins are the main antioxidant and antidiabetic active substances of F. dibotrys and are expected to be developed into potential antioxidant and hypoglycemic products.

Association of Human Papillomavirus Type 16 Long Control Region Variations with Cervical Cancer in a Han Chinese Population.

Objective: High-risk human papillomavirus (HPV) E6 and E7 proteins are the major oncoproteins involved in the tumorigenesis of cervical cancer. The long control region (LCR) in HPV plays an important role in regulating the expression of the E6 and E7 oncogenes. In the current study, we investigated the association of HPV16 LCR variations with cervical cancer. Methods: A total of 139 HPV16-positive cervical cancer patients (case group) and 116 HPV16-positive asymptomatic individuals (control group) were enrolled in the current study. Then, the HPV16 LCR was sequenced to determine the association between LCR variations and cervical cancer. Results: In the current study, HPV16 A1-A3 (19.4%), A4 (78.4%) and D3 (2.2%) variants were found in the case group. However, only A1-A3 (34.5%) and A4 variants (65.5%) were found in the control group. The distribution of the HPV16 variants between the case and control groups was significantly different (P=0.009). Moreover, a total of eleven variations (A7167G, A7173C, C7176T, C7200T, T7269C, C7286A, C7729A, C7763T, A7841G, G7867A and T24C) were significantly different between the case and control groups (P<0.05). For the sub-lineage analysis, only C7873G variations were significantly different between the case and control groups in the A4 (As) variant (P=0.039). Conclusion: Our results showed that specific variations in the HPV16 LCR were associated with cervical cancer. Our study will provide a good reference for further understanding of the relationship between HPV16 LCR variation and cervical cancer.

Physiological and transcriptome analysis reveal molecular mechanism in Salvia miltiorrhiza leaves of near-isogenic male fertile lines and male sterile lines.

BACKGROUND: Our previous study finds that male sterility in Salvia miltiorrhiza could result in stunted growth and reduced biomass, but their molecular mechanisms have not yet been revealed. In this article, we investigate the underlying mechanism of male sterility and its impact on plant growth and metabolic yield by using physiological analysis and mRNA sequencing (RNA-Seq). RESULTS: In this study, transcriptomic and physiological analysis were performed to identify the mechanism of male sterility in mutants and its impact on plant growth and metabolic yield. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, it is found that the pathways are mainly enriched in processes including organ development, primary metabolic process and secondary metabolic process. Physiological analysis show that the chloroplast structure of male sterile mutants of S. miltiorrhiza is abnormally developed, which could result in decrease in leaf gas exchange (A, E and gs), chlorophyll fluorescence (Fv, Fm and Fv/Fm), and the chlorophyll content. Expression level of 7 differentially expressed genes involved in photosynthesis-related pathways is downregulated in male sterile lines of S. miltiorrhiza, which could explain the corresponding phenotypic changes in chlorophyll fluorescence, chlorophyll content and leaf gas exchange. Transcriptomic analysis establishes the role of disproportionating enzyme 1 (DPE1) as catalyzing the degradation of starch, and the role of sucrose synthase 3 (SUS3) and cytosolic invertase 2 (CINV2) as catalyzing the degradation of sucrose in the S. miltiorrhiza mutants. The results also confirm that phenylalanine ammonialyase (PAL) is involved in the biosynthesis of rosmarinic acid and salvianolic acid B, and flavone synthase (FLS) is an important enzyme catalyzing steps of flavonoid biosynthesis. CONCLUSIONS: Our results from the physiological and transcriptome analysis reveal underlying mechanism of plant growth and metabolic yield in male sterile mutants, and provide insight into the crop yield of S. miltiorrhiza.

Polymorphisms in miRNA genes play roles in the initiation and development of cervical cancer.

MicroRNA deregulation is crucial for cancer development. Studies showed that polymorphisms in miRNA genes could affect miRNA expression, which might be associated with cancer development. In the current study, we investigated the association of seven single nucleotide polymorphisms (SNPs) in seven miRNA genes with the initiation and development of cervical cancer in a Chinese Han population. The SNPs of 358 cervical intraepithelial neoplasia (CIN) patients, 547 cervical cancer patients and 567 healthy individuals were genotyped using TaqMan assays. Moreover, we evaluated the association of the seven SNPs with the different stages of cervical cancer. Our results showed that rs4636297 in miR-126 was associated with susceptibility to CIN and cervical cancer (P=0.019 and 0.019, respectively) and that the T allele was associated with a higher risk of CIN (OR=1.334, 95% CI: 1.049-1.698) and cervical cancer (OR=1.296, 95% CI: 1.044-1.609). Similarly, rs11614913 in miR-125a was associated with CIN and cervical cancer (P=0.025 and 0.015, respectively), and the T allele might be the protective factor for CIN (OR=0.807, 95% CI: 0.669-0.974) and cervical cancer (OR=0.814, 95% CI: 0.689-0.961). Our results indicated that rs4636297 in miR-126 and rs11614913 in miR-196a2 play an important role only in the initiation of cervical cancer not in the development of CIN to cervical cancer.

Comparative proteomic study of liver lipid droplets and mitochondria in mice housed at different temperatures.

Laboratory mice are standardly housed at around 23 °C, setting them under chronic cold stress. Metabolic changes in the liver in mice housed at thermoneutral, standard and cold temperatures remain unknown. In the present study, we isolated lipid droplets and mitochondria from their livers in a comparative proteomic study aiming to investigate the changes. According to proteomic analysis, mitochondrial tricarboxylic acid cycle (TCA cycle) and retinol metabolism are enhanced, whereas oxidative phosphorylation is not affected obviously under cold conditions, suggesting that liver mitochondria may increase TCA cycle capacity in biosynthetic pathways, as well as retinol metabolism, to help the liver to adapt. Based on proteomic and immunoblotting results, perilipin 5 and major urinary proteins are increased significantly, whereas mitochondrial pyruvate carrier is decreased dramatically under cold conditions, indicating their involvement in liver adaptation.

Human papillomavirus type 16 E6 and E7 gene variations associated with cervical cancer in a Han Chinese population.

BACKGROUD: Human papillomavirus type 16 (HPV16) is a high-risk HPV subtype and a potent carcinogen. The HPV16 E6 and E7 genes are considered oncogenes that play a core role in the development of cervical cancer. METHODS: In the current study, we enrolled 97 HPV16-positive cervical cancer patients (case group) and 136 HPV16-positive asymptomatic individuals (control group) in a study to analyse the association between HPV16 E6 and E7 gene variations and cervical cancer. RESULTS: Our results showed that three HPV16 sub-lineages (A1-A3, A4 and D3) were present; the distribution of these variants between the case and control group was not significantly different (P = 0.178). When the distribution of the HPV16 E6 and E7 gene variations was compared, the distribution of only A131C (R10R) in the E6 gene showed a different trend between the case and control groups and C749T (S63F) in the E7 gene was significantly different between the case and control groups (P = 0.071 and P = 4.861 × 10-10, respectively). Regarding the sub-lineages, no variations in the E6 gene were significantly different between the case and control group for the A4 (As) and A1-A3 (EUR) sub-lineages. However, the distribution of C749T (S63F) in the E7 gene was significantly different between the case and control groups for the A4 (As) and A1-A3 (EUR) sub-lineages (P = 1.815 × 10-8 and P = 0.008). In the current study, we found that the C749T (S63F) variation in the HPV16 E7 gene was associated with cervical cancer not only in the A4 (As) sub-lineage but also in the A1-A3 (EUR) sub-lineage. CONCLUSION: Our study will provide a good reference for further functional studies of the relationship between cervical cancer carcinogenesis and the HPV16 E6 and E7 genes.