MiR-223-3p attenuates M1 macrophage polarization via suppressing the Notch signaling pathway and NLRP3-mediated pyroptosis in experimental autoimmune uveitis.

Autoimmune uveitis is an intraocular inflammatory disease with a high blindness rate in developed countries such as the United States. It is pressing to comprehend the pathogenesis of autoimmune uveitis and develop novel schemes for its treatment. In the present research, we demonstrated that the Notch signaling pathway was activated, and the level of miR-223-3p was significantly reduced in rats with experimental autoimmune uveitis (EAU) compared with the level of normal rats. To investigate the relationship between miR-223-3p and Notch signaling, EAU rats received miR-223-3p-carrying lentivirus, miR-223-3p vector-carrying lentivirus (miR-223-3p-N), and γ-secretase inhibitor (DAPT), respectively. The results of Q-PCR, immunological experiments, and flow cytometry analysis all support the hypothesis that both miR-223-3p and DAPT, a Notch signaling pathway inhibitor, had similar inhibitory effects on the EAU pathological process. That is to say, they could both inhibit the activation of the Notch signaling pathway via modulating recombination signal binding protein-Jκ (RBPJ) to restore the polarization imbalance of M/M2 macrophages in EAU rats. In addition, miR-223-3p could also inhibit NLRP3 inflammasome activation and inflammasome-induced pyroptosis in ocular tissues. Taken together, our findings indicate that miR-223-3p serves as an important regulator in M1 macrophage polarization and pyroptosis, thereby alleviating the inflammatory response in uveitis.

Management and follow-up of uveal effusion syndrome: a case report.

BACKGROUND: We present the management and follow-up of a case of uveal effusion syndrome (UES). CASE PRESENTATION: We study the relevant recent literature reports and review the aetiology, clinical classification, pathogenesis, diagnostic characteristics, treatment methods, and prognosis of this disease. When we encounter UES patients clinically, we can classify them according to their clinical characteristics and adopt different treatment plans for different types. The retina of this patient reattached 5 months after receiving eight periocular injections of triamcinolone acetonide (TA). CONCLUSIONS: For type III UES patients, local hormone therapy can be applied, and follow-up should be done to optimize the clinical outcome.

Glucocorticoids improve the balance of M1/M2 macrophage polarization in experimental autoimmune uveitis through the P38MAPK-MEF2C axis.

Uveitis is a common ocular disease that can induce serious complications and sequelae. It is one of the major causes of blindness. Currently, mounting evidence suggests that glucocorticoids (GCs) can suppress ocular inflammation and promote the healing of damaged ocular tissues, but the underlying mechanism remains unclear. The present study aimed to elucidate the mechanism by which GCs modulate the homeostasis of M1/M2 macrophage polarization in experimental autoimmune uveitis (EAU) through the p38MAPK-MEF2C axis. Female Lewis rats were randomly divided into four groups: a normal control (NC) group, an EAU group, an EAU + glucocorticoid (EAU + GC) group, and an EAU + p38MAPK inhibitor (EAU + SB) group. The EAU model was induced in EAU, EAU + GC, and EAU + SB groups, followed by the treatments of normal saline, GC (predisione), and SB203580, respectively. The findings demonstrated that the rats in GC and SB groups had much less ocular inflammation, and the clinical and pathological scores decreased. Further research revealed that GC and SB treatment could inhibit iNOS and CD86 expression while promoting Arg-1 and CD206 secretion in IRBP-induced uveitis rats. Moreover, we found that the role of GC was similar to the results of SB203580, but the role of GC was masked by the C16-PAF (a p38MAPK activator) treatment. Molecular docking and western blot results confirmed that GC's therapeutic action against EAU is mediated via the p38MAPK-MEF2C axis. It regulates macrophage polarization by encouraging M1 to M2 transition and releasing anti-inflammatory factors.

Study of Burden in Polycystic Ovary Syndrome at Global, Regional, and National Levels from 1990 to 2019.

Increasing attention has recently been paid to the harm of polycystic ovary syndrome (PCOS) to women. However, due to the inconsistency of global clinical diagnostic standards and the differing allocation of medical resources among different regions, there is a lack of comprehensive estimation of the global incidence and disability-adjusted life years (DALYs) of PCOS. Thus, it is difficult to assess the disease burden. We extracted PCOS disease data from 1990 to 2019 from the Global Burden of Disease Study (GBD) 2019 and estimated the incidence, DALYs, and the corresponding age-standardized rates (ASRs) of PCOS, as well as the socio-demographic index (SDI) quintiles, to describe epidemiological trends at the global level, encompassing 21 regions and 204 countries and territories. Globally, the incidence and DALYs of PCOS have increased. Its ASR also shows an increasing trend. Among them, the high SDI quintile seems relatively stable, whereas other SDI quintiles are constantly rising over time. Our research has provided clues regarding the disease pattern and epidemic trend of PCOS and analyzed the possible causes of disease burden in some specific countries and territories, which may have some value in health resource allocation and health policy formulation and prevention strategies.

Prednisone acetate modulates Th1/Th2 and Th17/Treg cell homeostasis in experimental autoimmune uveitis via orchestrating the Notch signaling pathway.

Uveitis is an immune eye disease that can seriously impair vision. Glucocorticoids (GCS) have been extensively used to treat uveitis, though the mechanisms have not been fully elucidated. In this study, we investigated the regulatory effects of prednisone acetate (PA) on the Th1/Th2 and Th17/Treg balance in experimental autoimmune uveitis (EAU) through modulating the Notch signaling pathway. Briefly, Lewis rats were randomly divided into the normal control (NC), EAU, and EAU + PA groups. Rats in EAU and EAU + PA groups were induced EAU, while those in the EAU + PA group were treated with PA. Clinical and histopathological scores were employed to assess the progression of EAU. The expression levels of Notch signaling-related molecules (Notch1, Notch2, Dll3, Dll4, and Rbpj) and Th-associated cytokines (IFN-γ, IL-4, IL-10, and IL-17) were assessed via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the frequencies of Th1, Th2, Th17 and Treg cells were detected by flow cytometry. These experimental results indicated that activation of the Notch signaling pathway occurred in EAU rats and resulted in a severe imbalance of the Th17/Treg and Th1/Th2 ratios. PA treatment significantly alleviated ocular inflammation, inhibited activation of the Notch signaling pathway, and declined Th1, and Th17 cell differentiation, thereby restoring the Th1/Th2 and Th17/Treg balance. Collectively, PA can positively enhance the systemic immune response and improve the intraocular microenvironmental homeostasis by inhibiting activation of the Notch signaling pathway and by restoring Th1/Th2 and Th17/Treg balance, thus achieving the goal of treating uveitis.

Recent Advances in the Processing and Manufacturing of Plant-Based Meat.

Plant protein technology is a core area of biotechnology to ease the problem of human protein demand. Plant-based meat based on plant protein technology is a growing concern by global consumers in alleviating environmental pollution, cutting down resources consumption, and improving animal welfare. Plant-based meat simulates the texture, taste, and appearance of animal meat by using protein, lipid, carbohydrate, and other plant nutrients as the main substances. This review summarizes the main components of plant-based meat, processing technology, standard formula, market competition, and formula and texture of future research directions. According to the existing methods of plant-based meat fiber forming, the development process and characteristics of four production processes and equipment of plant-based meat spinning, extrusion, shearing, and 3D printing are emphatically expounded. The processing principles and methods of different processing technologies in plant-based meat production are summarized. The production process and equipment of plant-based meat will pay more attention to the joint production of various processes to improve the defects of plant-based meat production process.

Double vitrification-warming cycles, coupled with blastocyst biopsy, impair live birth but do not affect neonatal outcomes.

OBJECTIVE: To identify whether the transfer of blastocysts that have been vitrified, thawed, biopsied, revitrified, and subsequently rethawed affects clinical outcome and neonatal outcome. METHODS: A retrospective study was conducted in a single assisted reproduction technology center from September 2016 to March 2021. Women undergoing single frozen euploid blastocysts transfer were stratified into two groups based on number of vitrification-thawing cycles: single vitrification coupled with single biopsy (group A, n = 177) and double vitrification coupled with single biopsy (group B, n = 30). Pregnancy and perinatal outcomes of the two groups were compared. RESULTS: Clinical pregnancy rates were similar between the two groups. Group B was associated with an increased likelihood of live birth when compared with group A by different multivariable analysis models (model 1: odds ratio, 0.42 [95% confidence interval, 0.18-0.97], P = 0.041; model 2: odds ratio, 0.38 [95% confidence interval, 0.16-0.92], P = 0.033). No major obstetrical complication was reported in the two groups and only one malformation live birth was reported in group A. CONCLUSION: The procedure of double vitrification-warming cycles, coupled with single biopsy, increases pregnancy loss and ultimately diminishes live birth but does not affect perinatal outcome. Future studies with a larger sample size would help to validate the results.

Natural cycle increases the live-birth rate compared with hormone replacement treatment for frozen-thawed single euploid blastocyst transfer.

Background: A number of studies have compared the clinical outcomes between the two endometrial preparation methods: natural cycles (NCs) and hormone replacement treatment (HRT) before frozen embryo transfer, but the results were conflicting. In order to mitigate the potential effect of embryos per se, several researchers have worked on this subject for euploid blastocyst transfer, but the results were still inconsistent. Therefore, the present study was aimed to investigate the clinical outcomes between HRT and NC for autologous single vitrified-warmed euploid blastocyst transfer based on our data. Methods: A total of 598 frozen-thawed single euploid blastocyst transfer cycles in the assisted reproductive center of Northwest Women's and Children's Hospital from January 2014 to May 2021 were retrospectively analyzed. Women were stratified into the NC (n = 125) or HRT (n = 473) group according to the patient's preference and the physician's guidance. Multivariate regression models and subgroup analysis were constructed to analyze the association between endometrial preparation and live birth. Results: Women in the NC group had a higher live birth rate (68.80% versus 58.35%, P = 0.034) and a lower risk of total pregnancy loss (8.51% versus 21.14%, P = 0.005) when compared with women in the HRT group. The biochemical pregnancy rate (75.20% versus 74.00%, P = 0.784) and clinical pregnancy rate (74.40% versus 69.98%, P = 0.334) were similar between the two groups (NC versus HRT). NC was associated with an increased odds of live birth compared with HRT by different multivariable analysis models (Model 1: adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.57, 0.36 - 0.90; Model 2: aOR, 95%CI: 0.57, 0.35 - 0.92). In addition, the increased chance of live birth in the NC group was found in all subgroups. No major obstetrical complications and two malformation livebirths were reported. Conclusions: In women undergoing single euploid frozen blastocyst transfers, the NC group was associated with a lower pregnancy loss rate and an ultimately higher live birth rate than the HRT group. Although HRT is convenient for both clinicians and patients, the lower live birth rate should be taken into account and NC might be the first choice of endometrial preparation method.

Scream Sound-induced Chronic Psychological Stress Results in Diminished Ovarian Reserve in Adult Female Rat.

It is well established that chronic psychological stress (PS) induces female reproductive dysfunction. However, the studies on the consequences of chronic PS exposure precisely targeting ovarian reserve are lacking. In the present study, we employed a chronic scream sound-induced PS model to investigate the potential effect of pure psychosocial stressors on ovary reserve. Female rats were subjected to scream sound stress, white noise, or background for 3 weeks. Animals were euthanized by cervical dislocation after stress for collection of blood or ovaries. Sex hormones were analyzed by enzyme-linked immunosorbent assay. The follicle number was examined by histopathology. Granulosa cell apoptosis of the ovaries was examined by in situ cell death detection kit. Finally, rats were mated with proven fertile male rats to study fertility parameters. Female rats exposed to scream sound were presented with reduced weight gain and sucrose preference, while immobility time in forced swim test and serum corticosterone concentration were significantly increased. Scream sound stress sequentially decreased plasma anti-Müllerian hormone and estradiol concentration, induced primordial and preantral follicles loss, augmented granulosa cell apoptosis in ovarian growing follicles, and eventually decreased litter sizes. Based on these results, we suggest that chronic PS induced loss of ovarian reserve by accelerated primordial follicle activation and destruction of growing follicles, which results in follicle depletion and decreased fertility.

Is duration of estrogen supplementation associated with clinical outcomes in frozen-thawed autologous single-blastocyst transfer cycles?

PURPOSE: To investigate the relationship between different duration of estrogen administration and live birth rate (LBR) after autologous single frozen blastocyst transfer with hormone replacement therapy. METHODS: A total of 2026 frozen blastocyst transfer cycles in the assisted reproductive center of northwest women and children's hospital from January, 2017, to August, 2020, were retrospectively analyzed. All the cycles were allocated into 3 groups according to the duration of estrogen administration: group A, 11-14 days (n = 346); group B, 15-18 days (n = 1191), and group C, ≥ 19 days (n = 489). Baseline data, clinical, and perinatal outcomes of the three groups were compared. A multivariate regression model was constructed to analyze the association between duration of estradiol administration and clinical outcomes. RESULTS: We did not observe a significant association between duration of estrogen supplementation and LBR in group B (adjusted odds ratio [aOR] 1.14; 95% confidence interval [CI], 0.89-1.45) or group C (aOR 1.16; 95% CI, 0.86-1.56) patients with group A as the reference group, through logistic regression analysis. No statistical differences were observed in perinatal outcomes among the three groups. CONCLUSION: The duration of estrogen administration was not associated with the likelihood of live birth in women undergoing frozen-thawed autologous single-blastocyst transfer.

Epigallocatechin gallate enhances human lens epithelial cell survival after UVB irradiation via the mitochondrial signaling pathway.

The aim of the present study was to explore the mechanism underlying the ultraviolet B (UVB) irradiation­induced apoptosis of human lens epithelial cells (HLECs), and to investigate the protective effect of epigallocatechin gallate (EGCG) against the UVB­induced apoptosis of HLECs. HLECs were exposed to different concentrations of EGCG plus UVB (30 mJ/cm2). Cell viability was determined using the MTT assay. Furthermore, mitochondrial membrane potential (Δψm) and apoptosis were assessed by flow cytometry with JC­1 and Annexin V/PI staining, respectively. Moreover, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH­Px), as well as the levels of GSH, hydrogen peroxide (H2O2) and hydroxyl free radicals were determined using biochemical assay techniques. Reverse transcription­quantitative PCR and western blotting were used to detect the mRNA and protein expression levels of Bcl­2, Bax, cytochrome c, caspase­9 and caspase­3, respectively. The results revealed that UVB irradiation reduced the Δψm of HLECs and induced apoptosis. Notably, EGCG significantly attenuated the generation of H2O2 and hydroxyl free radicals caused by UVB irradiation in HLECs, and significantly increased CAT, SOD and GSH­Px activities, however, the GSH levels were not significantly increased. EGCG also reduced UVB­stimulated Bax, cytochrome c, caspase­9 and caspase­3 expression, and elevated Bcl­2 expression, suggesting that EGCG may possess free radical­scavenging properties, thus increasing cell viability. In conclusion, EGCG may be able to protect against UVB­induced HLECs apoptosis through the mitochondria­mediated apoptotic signaling pathway, indicating its potential application in clinical practice.

Reduced Plasma Levels of α-Klotho and Their Correlation With Klotho Polymorphisms in Elderly Patients With Major Depressive Disorders.

Background: Recent literature suggests that α-Klotho, a widely recognized anti-aging protein, is involved in longevity as well as in many diseases, including Alzheimer's disease, and depression. Although the Klotho gene encodes α-Klotho, a single transmembrane protein with intracellular and extracellular domains, the relationship between Klotho gene polymorphism and circulating α-Klotho levels in patients with major depressive disorder (MDD) is not clear. Methods: A total of 144 MDD patients and 112 age-matched healthy controls were included in this study. The Klotho genetic polymorphisms (rs9536314, rs9527025, and rs9315202) and plasma α-Klotho levels were measured by PCR and ELISA, respectively. The severity of depressive symptoms was estimated using the Hamilton Depression Scale (HAMD). Results: We found a significantly lower level of plasma α-Klotho in the MDD patients than in controls. Among them, only elderly MDD patients (first episode) showed significantly lower α-Klotho levels than the age-matched controls, while elderly recurrent and young MDD patients showed no difference in plasma α-Klotho levels from age-matched controls. The young MDD group showed a significantly earlier onset age, higher plasma α-Klotho levels, and lower HAMD scores than those in the elderly MDD group. While the plasma α-Klotho levels were higher in rs9315202 T alleles carrier regardless age or sex, the rs9315202 T allele was negatively correlated with disease severity only in the elderly MDD patients. Conclusion: The results of our study showed that only elderly MDD patients showed a decrease in plasma α-Klotho levels along with an increase in disease severity as well as an association with the number of rs9315202 T alleles, and not young MDD patients compared to age-matched controls. Our data suggest that circulating α-Klotho levels combined with Klotho genetic polymorphisms are important in elderly MDD patients, particularly carriers of the Klotho gene rs9315202 T allele.

Insights on the interaction mechanism of exemestane to three digestive enzymes by multi-spectroscopy and molecular docking.

Exemestane is an irreversible steroidal aromatase inhibitor, typically used to treat breast cancer. As an anti-tumor drug, exemestane has more obvious side effects on the gastrointestinal tract. The purpose of this work is to investigate the combination of exemestane with three important digestive enzymes including pepsin (Pep), trypsin (Try) and α-Chymotrypsin (α-ChT) so as to analyze the mechanism of the gastrointestinal adverse effects causing by exemestane binding. Enzyme activity experiment showed that the enzyme activity of Pep was decreased in the presence of exemestane. Fluorescence spectra revealed that exemestane formed stable complexes with digestive enzymes, and the quenching mechanism of drug-digestive enzymes interaction were all static quenching. The binding constants of Pep, Try and α-ChT at 298 K were 2.34 × 105, 1.45 × 105, and 2.05 × 105 M-1, respectively. Synchronous fluorescence and 3D fluorescence spectroscopy showed that the conformation of exemestane was slightly changed after combining with digestive enzymes, and non-radiative energy transfer occurred. Circular dichroism results indicated that exemestane could change the secondary structure of digestive enzymes via increase the α-helix content and decrease in the ß-sheet content. Thermodynamic parameters (ΔH0, ΔS0, and ΔG0) revealed that exemestane interacted with α-ChT through electrostatic force, and the binding force with Pep and Try was van der Waals interactions and hydrogen, which was basically consistent with the molecular docking results.

Promoter hypermethylation of SOX11 promotes the progression of cervical cancer in vitro and in vivo.

The development of cervical cancer (CC) is a multi­gene, multi­step carcinogenic process that involves complex genetic and epigenetic mechanisms. SRY­related HMG­box gene 11 (SOX11) is a member of the SOX family of transcription factors with an emerging crucial role in the development of various tumor types. To elucidate the function of SOX11 in cervical carcinogenesis, the expression level of SOX11 during the development of human CC was analyzed by immunohistochemistry and western blot analysis. Additionally, the methylation status of the SOX11 was examined using bisulfite sequencing and methylation­specific polymerase chain reaction. The SOX11 expression and promoter methylation in human CC cell lines were also determined. The effect of SOX11 expression restoration after 5­aza­2'­deoxycytidine (5­Aza­dC) treatment on the CC cell proliferation ability was evaluated in CC cell lines. SOX11 was highly expressed in normal cervix (NC) and precancerous low­grade squamous intraepithelial lesions, but weakly expressed or virtually absent in precancerous high­grade squamous intraepithelial lesions and CC, which is consistent with the result of the western blot analysis. Hypermethylation of the SOX11 promoter was detected in CC, which was significantly higher than that in NC samples at each CpG site. The expression level of SOX11 in the CC cell lines was downregulated compared with the positive control, Tera­1human teratoma cell line. Upon 5­Aza­dC treatment, SOX11 expression was significantly upregulated in the CC cell lines at the mRNA and protein levels, and cell proliferation was inhibited. The results indicated that the downregulation of SOX11 in CC is due to the hypermethylation of the SOX11 promoter region. Thus, SOX11 methylation may have a role in the growth of CC cells and cervical carcinogenesis.

Identification of Significant Gene Signatures and Prognostic Biomarkers for Patients With Cervical Cancer by Integrated Bioinformatic Methods.

Cervical cancer is the leading cause of death with gynecological malignancies. We aimed to explore the molecular mechanism of carcinogenesis and biomarkers for cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing details of 254 cervical squamous cell carcinomas and 3 normal samples from The Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network analysis of differentially expressed genes were performed. Then, we conducted pathway enrichment analysis for modules acquired in protein-protein interaction analysis and obtained a list of pathways in every module. After intersecting the results from the 3 approaches, we evaluated the survival rates of both mutual pathways and genes in the pathway, and 5 survival-related genes were obtained. Finally, Cox hazards ratio analysis of these 5 genes was performed. DNA replication pathway ( P < .001; 12 genes included) was suggested to have the strongest association with the prognosis of cervical squamous cancer. In total, 5 of the 12 genes, namely, minichromosome maintenance 2, minichromosome maintenance 4, minichromosome maintenance 5, proliferating cell nuclear antigen, and ribonuclease H2 subunit A were significantly correlated with survival. Minichromosome maintenance 5 was shown as an independent prognostic biomarker for patients with cervical cancer. This study identified a distinct pathway (DNA replication). Five genes which may be prognostic biomarkers and minichromosome maintenance 5 were identified as independent prognostic biomarkers for patients with cervical cancer.

Identification and validation of the role of matrix metalloproteinase-1 in cervical cancer.

Lymph node (LN) metastasis at an early stage of cervical cancer is often an indicator of poor prognosis and is critical for subsequent adjuvant therapy. The current study aimed to identify aberrant gene signatures and biomarkers of metastasis for patients with cervical cancer. RNA-sequencing data of 132 LN negative (N0) and 60 LN positive (N1) cervical cancer samples obtained from The Cancer Genome Atlas database were analyzed. Differentially expressed genes were identified using R packages 'edgeR' and 'limma'. Kyoto Encyclopedia of Genes and Genomes pathway enrichment and Gene Set Enrichment Analysis (GSEA) were conducted. The GSE9750 dataset obtained from Gene Expression Omnibus was analyzed to identify genes that are persistently aberrantly expressed during the development of cervical cancer. The peroxisome proliferator-activated receptor (PPAR) signaling pathway was screened out to be significant during LN metastasis. In the two analyzed datasets, 11 genes were aberrantly expressed, while matrix metalloproteinase 1 (MMP1) was the only gene that was persistently overexpressed. Cell viability, wound healing and Transwell assays were performed to evaluate the effects of MMP1 knockdown in cervical cancer cell lines, and the expression of epithelial mesenchymal transition (EMT) markers was detected. Finally, the clinical significance of MMP1 was investigated. The current study identified that MMP1 was overexpressed and the PPAR signaling pathway was associated LN metastasis in patients with cervical cancer. Following knockdown of MMP1, the proliferation, migration and invasion of cervical cancer cell lines were weakened, the expression of epithelial marker E-cadherin was increased, and the expression of metastasis-associated gene vimentin was decreased. MMP1 was an independent prognostic factor for cervical cancer. The current study indicated that MMP1 has a key role in the regulation of cervical tumor growth and LN metastasis via EMT to a certain extent. The results suggest that MMP1 may be a biomarker for LN metastasis of cervical cancer, and further validation should be performed.

Identification of a histone family gene signature for predicting the prognosis of cervical cancer patients.

Heterogeneity in terms of tumor characteristics, prognosis, and survival among cancer patients is an unsolved issue. Here, we systematically analyzed the aberrant expression patterns of cervical cancer using RNA-Seq data from The Cancer Genome Atlas (TCGA). We incorporated gene profiling, molecular signatures, functional and pathway information with gene set enrichment and protein-protein interaction (PPI) network analysis, to identify sub-networks of genes. Those identified genes relating to DNA replication and DNA repair-mediated signaling pathways associated with systemic lupus erythematosus (SLE). Next, we combined cross-validated prognostic scores to build an integrated prognostic model for survival prediction. The combined approach revealed that the DNA repair-mediated including the functional interaction module of 18 histone genes (Histone cluster 1 H2A, B and H4), were significantly correlated with the survival rate. Furthermore, five of these histone genes were highly expressed in three cervical cancer cohorts from the Oncomine database. Comparison of high and low histone variant-expressing human cervical cancer cell lines revealed different responses to DNA damage, suggesting protective functions of histone genes against DNA damage. Collectively, we provide evidence that two SLE-associated gene sets (HIST1H2BD and HIST1H2BJ; and HIST1H2BD, HIST1H2BJ, HIST1H2BH, HIST1H2AM and HIST1H4K) can be used as prognostic factors for survival prediction among cervical cancer patients.

Msi1 promotes tumor progression by epithelial-to-mesenchymal transition in cervical cancer.

Musashi1 (Msi1) is an RNA-binding protein that has been reported to be a pivotal regulator in tumorigenesis and progression in several cancers. However, its function and mechanism in cervical cancer is still unknown. In this study, Msi1 expression was found elevated in cervical cancers by immunohistochemistry and correlated with poor outcomes. Then, endogenous Msi1 was silenced in cervical cancer cell lines by short hairpin RNA, and its function and mechanism were determined. The results showed that the silencing of Msi1 in SiHa and HeLa cells inhibited the cells' migratory and invasive abilities in vitro and tumor progression in vivo. Epithelial-to-mesenchymal transition (EMT) markers were down-regulated, and Wnt activity was inhibited by the silencing of Msi1. In clinical tissues, positive correlations between Msi1 and EMT markers were found. In conclusion, Msi1, a diagnostic marker and potential therapeutic target, promoted the EMT progression through activation of the Wnt signaling pathway in cervical cancers, thereby contributing to poor prognosis.

Macular Abnormalities in Chinese Patients with Uveitis.

PURPOSE: To investigate the prevalence of macular abnormalities in Chinese patients affected by uveitis. METHODS: A retrospective study was performed by reviewing the medical records and high-definition spectral domain optical coherence tomography (SD-OCT) scans in a cohort of 413 uveitis eyes to assess the presence of macular abnormalities. RESULTS: Macular abnormalities were observed in 242 (58.6%) of the 413 examined eyes with uveitis. The observed macular abnormalities include diffuse macular edema, cystoid macular edema (CME), and serous retinal detachment. In addition, vitreoretinal abnormalities in the patients with uveitis were evaluated through SD-OCT. The evaluated vitreoretinal abnormalities include epiretinal membrane, tractional CME, macular adhesions, macular hole, and choroidal neovascularization. The most frequent abnormality in the uveitis patients was CME, observed in 105 eyes (25.4%), and followed by epiretinal membrane, observed in 52 eyes (12.6%). Moreover, the percentage of uveitis patients with vitreoretinal abnormalities (23.1%) was significantly high. CONCLUSIONS: Macular abnormalities were more frequently observed in uveitis compared with those in the general population. Multiple patterns of macular abnormalities indicate lesions of multilayer of cells. Therefore, when following up uveitis patients, it is highly recommended to screen with SD-OCT to evaluate the macular alterations of those patients. Careful observation of the macular abnormalities using SD-OCT may help to identify patients who are at risk for visual loss secondary to foveal changes and provide preventive treatment.

The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer.

Enhancer of zeste 2 (EZH2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH2 is associated with cervical cancer progression, particularly the progression to invasive squamous cell carcinoma. Enhancer of zeste 2 is known to trimethylate lysine 27 on histone H3, leading to gene silencing that contributes to the progression of tumours into a more aggressive form of cancer. However, the specific molecular mechanisms by which EZH2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH2 inhibitor was reported to selectively inhibit trimethylated lysine 27 on histone H3 and to reactivate silenced genes in cancer cells. In this study, we found that GSK343 (a specific inhibitor of EZH2 methyltransferase) induces phenotypic reprogramming of cancer cells from mesenchymal to epithelial cells, reducing proliferation and cell motility and blocking the invasion of cervical cancer cell lines both in vitro and in vivo. Treatment with the EZH2 inhibitor led to increased levels of the epithelial marker E-cadherin and decreased levels of mesenchymal markers such as N-cadherin and vimentin. The observed reprogramming is associated with restrained cervical cancer progression and provides direct evidence in support of EZH2 as a therapeutic target.