Percutaneous transhepatic stenting for acute superior mesenteric vein stenosis after pancreaticoduodenectomy with portal vein reconstruction: A case report.

BACKGROUND: Percutaneous transhepatic stent placement has become a common strategy for the postoperative treatment of portal vein (PV)/superior mesenteric veins (SMV) stenosis/occlusion. It has been widely used after liver transplantation surgery; however, reports on stent placement for acute PV/SMV stenosis after pancreatic surgery within postoperative 3 d are rare. CASE SUMMARY: Herein, we reported a case of intestinal edema and SMV stenosis 2 d after pancreatic surgery. The patient was successfully treated using stent grafts. Although the stenosis resolved after stent placement, complications, including bleeding, pancreatic fistula, bile leakage, and infection, made the treatment highly challenging. The use of anticoagulants was adjusted multiple times to prevent venous thromboembolism and the risk of bleeding. After careful treatment, the patient stabilized, and stent placement effectively managed postoperative PV/SMV stenosis. CONCLUSION: Stent placement is effective and feasible for treating acute PV/SMV stenosis after pancreatic surgery even within postoperative 3 d.

Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

[Clinical Study of Allogeneic Hematopoietic Stem Cell Transplantation Patients with Co-Reactivation of Cytomegalovirus and Epstein-Barr Virus].

OBJECTIVE: To explore the clinical characteristics and risk factors of cytomegalovirus(CMV) and Epstein-Barr virus(EBV) co-reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its influence on prognosis. METHODS: The clinical data of 222 patients who received allo-HSCT from January 2015 to December 2020 were collected, and the patients were divided into groups according to the occurrence of CMV and EBV infection. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard regression model was used to analyze the risk factors of co-reactivation of CMV and EBV. RESULTS: After allo-HSCT, there were 30 patients with co-reactivation of CMV and EBV (CMV++EBV+ group), 101 patients with CMV viremia (CMV+ group), 149 patients with EBV viremia (EBV+ group), and 28 patients with CMV and EBV inactivation (CMV-+ EBV- group). Compared with the other groups, the incidence of acute graft-versus-host disease (aGVHD) and hemorrhagic cystitis (HC) was higher in CMV++ EBV+ groups (53.3% vs 42.6%, 36.9%, 17.9%, P < 0.001; 36.7% vs 32.7%, 22.8%, 10.7%, P =0.042). The incidence of post-transplant lymphoproliferative disease (PTLD) in CMV++ EBV+ group was similar to CMV+ group and EBV+ group (3.3% vs 3.0%, 3.4%, P =0.811). Univariate and multivariate analysis showed that the persistent time of CMV and EBV after transplantation were independent risk factors for co-reactivation of CMV and EBV. Compared with the other groups, the 2-year overall survival (OS) rate and 2-year disease-free survival (DFS) rate of patients in CMV++EBV+ group were lower (46.7% vs 74.9%, 83.4%, 71.4%, P < 0.001; 46.7% vs 70.9%, 79.5%, 69.9%, P =0.002), and 2-year non-recurrence mortality (NRM) was higher (48.2% vs 22%, 13.6%, 18.7%, P <0.001). CONCLUSION: The persistent time of CMV and EBV after transplantation are independent risk factors for patients with co-reactivation of CMV and EBV. Patients with co-reactivation of CMV and EBV had lower OS and DFS rate and higher NRM, suggesting that the clinical prognosis of the patients are worse.

Brunonianines A-C, C20-diterpenoid alkaloids with cyano group from Delphinium brunonianum Royle.

Cyano tends to have better biological activity, but it is rarely reported in natural products, especially in the C20-diterpene alkaloids. Herein, three unprecedented C20-diterpenoid alkaloids, brunonianines A-C (1-3), possessing rare cyano functional group as well as an atisine backbone constructed from a phenethyl substituent and a tetrahydropyran ring, along with four C19-alkaloids (4-7) and one amide alkaloids (8), were isolated from the whole plant of Delphinium brunonianum Royle. Compounds 1-3 are also the first atisine type diterpenoid alkaloids with cyano group obtained from nature. The structures of the previously undescribed compounds were elucidated by HR-ESI-MS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations and single-crystal X-ray diffraction. Reasonable speculations have also been made regarding the biogenic synthetic pathways of compounds 1-3. In addition, the inhibitory activity of all compounds was also tested against four tumor lines: A549, Caco-2, H460 and Skov-3, where compound 2 (IC50 2.20 ± 0.21 µM) showed better inhibitory activity against Skov-3 cells than the hydroxycamptothecin. Using flow cytometry, cell staining, migration and invasion analysis, and Western blot, compound 2 was found to arrest cells in the G2/M phase and was able to effectively inhibit cell motility to achieve potent anti-tumor effects. In addition, compound 2 can effectively induce apoptosis by activating the Bax/Bcl-2/Caspase-3 signaling pathway.

Two new 2-arylbenzo[b]furans from Itea indochinensis and their anti-hepatocellular carcinoma and anti-oxidant effects.

Two new 2-arylbenzo[b]furans (1-2) and ten known compounds (3-12) were identified from the 95% EtOH extract of the branches and leaves of Itea indochinensis for the first time. Their structures were determined mainly based on extensive analyses of UV, IR, 1D/2D NMR and HRMS spectra. The results of MTT assays demonstrated the anti-tumor potential of compound 1 with good selectivity, which displayed moderate inhibitory effects on proliferation of SK-hep-1 cells with IC50 value of 22.3 µM, while weak inhibitory effect on proliferation of HepG2 cells with an inhibition rate of 25% at 20 µM, and no obviously inhibitory effect on proliferation of A549 cells at 20 µM. In addition, compound 1 exhibited its significant scavenging capacity on ABTS·+ free radical with an IC50 value of 0.11 mg/mL, while weak scavenging effects on DPPH and O2·- radicals with scavenging ratios of 32.93% and 21.49% at 1 mg/mL, respectively.

Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.

Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-ß signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.

Risk Factors for Residual Back Pain After PVP Treatment for osteoporotic Thoracolumbar Compression Fractures: A Retrospective Cohort Study.

OBJECTIVES: To explore the risk factors of residual back pain after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fracture (OVCF). METHODS: We retrospectively reviewed the records of 675 patients with OVCF treated with PVP from January 2015 to January 2020. Postoperative back pain intensity was assessed by the VAS score. Residual back pain was defined as the presence of postoperative moderate-severe pain (average VAS score≥4), and the variables included patient characteristics, baseline symptoms, imaging data and operation-related factors. Risk factors were identified with univariate and multivariate logistic regression analysis. RESULTS: Residual back pain occurred in 46 of the 675 patients included in the study, with an incidence rate of 6.8%. Multivariate logistic regression analysis showed that low Pre-BMD (OR = 3.576, P = 0.041), multiple vertebral fractures (OR = 2.795, P = 0.026), posterior fascia injury (OR = 4.083, P = 0.032), cement diffusion volume rate <0.2 (OR = 3.507, P = 0.013), facet joint violation (OR = 11.204, P < 0.001), and depression (OR = 3.562, P = 0.035) were positively correlated with residual back pain after PVP. CONCLUSIONS: Low pre-BMD (pre-bone mineral density), multiple vertebral fractures, posterior fascia injury, cement diffusion volume rate <0.2, facet joint violation and depression were the independent risk factors of residual back pain after PVP.

The effect of CALIPER-derived parameters for idiopathic pulmonary fibrosis in predicting prognosis, progression, and mortality: a systematic review.

BACKGROUND: High-resolution computed tomography (HRCT), as the main tool for monitoring idiopathic pulmonary fibrosis (IPF), is characterized by subjective variability among radiologists and insensitivity to subtle changes. Recently, a few studies have aimed to decrease subjective bias by assessing the severity of IPF using computer software, i.e., Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER). However, these studies had diverse research directions. In this review, we systematically assess the effect of CALIPER in the management of IPF. METHODS: A systematic review was conducted through a search of published studies in PubMed, Web of Science, Cochrane, Embase, Scopus, and CNKI databases from database inception through February 28, 2022. The methodological quality would be evaluated by using Methodological Index for Non-Randomized Studies (MINORS). Narrative synthesis summarized findings by participant characteristics, study design, and associations with outcomes. RESULTS: Ten studies were included. They evaluated the relationship between CALIPER-derived parameters and pulmonary function test (PFT) and mortality. CALIPER-derived parameters showed a significant correlation with PFT and mortality. Two studies reported that CALIPER could be used to stratify outcomes. CONCLUSION: CALIPER-derived parameters can be used to evaluate prognosis and mortality. CALIPER-derived parameters combined with composite physiologic index (CPI) or Gender-Age-Physiology (GAP) could help clinicians implement targeted management by refining prognostic stratification. However, research has been constrained by small number of retrospective investigations and sample sizes. Therefore, it is essential to design prospective controlled studies and establish the staging system by CALIPER-derived parameters and combining them with CPI, FVC, or GAP. CLINICAL RELEVANCE STATEMENT: It is beneficial for clinic to provide objective, sensitive, and accurate indicators of disease progression. It also helps the clinic to develop individualized treatment plans based on the stage of disease progression and provides evaluation of efficacy in drug trials. KEY POINTS: • Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) is a quantitative CT analysis software that can be used to evaluate the progression of disease on CT. • The CALIPER-derived vessel-related structure shows great performance in the management of idiopathic pulmonary fibrosis. • CALIPER-derived parameters combined with composite physiologic index or Gender-Age-Physiology can be used to refine prognostic stratification.

Enhancing sludge methanogenesis with changed micro-environment of anaerobic microorganisms by Fenton iron mud.

Conductive materials have been demonstrated to enhance sludge methanogenesis, but few researches have concentrated on the interaction among conductive materials, microorganisms and their immediate living environment. In this study, Fenton iron mud with a high abundance of Fe(III) was recycled and applied in anaerobic reactors to promote anaerobic digestion (AD) process. The results show that the primary content of extracellular polymeric substances (EPS) such as polysaccharides and proteins increased significantly, possibly promoting microbial aggregation. Furthermore, with the increment of redox mediators including humic substances in EPS and Fe(III) introduced by Fenton iron mud, the direct interspecies electron transfer (DIET) between methanogens and interacting bacteria could be accelerated, which enhanced the rate of methanogenesis in anaerobic digestion (35.21 ± 4.53% increase compared to the control). The further analysis of the anaerobic microbial community confirmed the fact that Fenton iron mud enriched functional microorganisms, such as the abundance of CO2-reducing (e.g. Chloroflexi) and Fe(III)-reducing bacteria (e.g., Tepidimicrobium), thereby expediting the electron transfer reaction in the AD process via microbial DIET and dissimilatory iron reduction (DIR). This work will make it possible for using the recycled hazardous material - Fenton iron mud to improve the performance of anaerobic granular sludge during methanogenesis.

Patient-controlled intravenous administration of dexmedetomidine with nalbuphine versus sufentanil for post cesarean delivery analgesia: A retrospective observational study.

This retrospective observational study aims to investigate the patient-controlled intravenous analgesia (PCIA) of dexmedetomidine (DEX) with nalbuphine (NAL) versus sufentanil (SUF) for post-cesarean delivery management. A total of 300 women were evaluated who underwent cesarean section surgery with combined spinal-epidural anesthesia. After surgery, all patients were connected to a patient-controlled analgesia pump. The PCIA protocol was programmed with 0.11 µg/kg/h DEX in combination with 0.03 µg/kg/h SUF in Group I (n = 150) or 0.11 µg/kg/h DEX in combination with 0.03 mg/kg/h NAL in Group II (n = 150). There was no significant difference in incision pain and sedation level between the two groups within 48 h after the surgery assessed by visual analog scale (VAS) and Ramsay sedation scale, respectively. However, at 2, 6, 12, and 24 h after surgery, visceral pain at rest and at mobilization was alleviated in the Group II as compared with the Group I with lower VAS scores. Moreover, fewer adverse reactions were found in the Group II when compared with Group I, including postpartum respiratory depression, nausea/vomiting, urinary retention, and cardiovascular events. Overall, there was an increased patient satisfaction in the Group II as compared with the Group I. Based on the results of this study, it seems that adding NAL to PCIA with DEX, as compared to SUF with DEX, have an effect on reducing the intensity of visceral pain after cesarean section with less adverse reactions and higher patient satisfaction.

[QuEChERS-liquid chromatography-tandem mass spectrometry for determination of 22 triazole pesticide residues in Chinese herbal medicines].

Eight well-known herbals in Zhejiang Province, Zhebawei, are commonly used as traditional Chinese herbal medicines owing to their rich active ingredients. However, the unavoidable use of pesticides during agricultural production has led to pesticide residue problems in these herbs. In this study, a simple, rapid, and accurate method was established to determine 22 triazole pesticide residues in Zhebawei. An improved QuEChERS method was used for sample pretreatment, and Rhizoma Atractylodis Macrocephalae was used as a representative sample. The sample was extracted with acetonitrile to eliminate some polar and nonpolar compounds, pigments, and other impurities, and the purification effects of multiwalled carbon nanotubes (MWCNTs), amino-modified multiwalled carbon nanotubes (MWCNTs-NH2), carboxylated multiwalled carbon nanotubes (MWCNTs-COOH), crosslinked polyvinylpyrrolidone (PVPP), zirconium dioxide (ZrO2), 3-(N,N-diethylamino)-propyltrimethoxysilane (PSA), octadecyl (C18), and graphitized carbon black (GCB) were compared. MWCNTs-COOH and C18 were selected as the purification adsorbents, and their dosages were systematically optimized. The combination of 10 mg of MWCNTs-COOH and 20 mg of C18 was eventually selected as the purification adsorbents. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for analysis, and box graphs were plotted to present the dispersion of each group of recoveries, thus enabling the identification of the data outliers, dispersion distribution, and data symmetry. The established method was systematically verified and showed good linearity over the concentration range of 1-200 µg/L (except for bromuconazole, epoxiconazole, and etaconazole) with correlation coefficients >0.99. The average recoveries of the 22 pesticides at spiked levels of 10, 20, 100, and 200 µg/kg were in the range of 77.0%-115% with relative standard deviations (RSDs) <9.4%. The limits of detection and quantification were 1-2.5 µg/kg and 10-20 µg/kg, respectively. The applicability of the developed method to other herbals was investigated at 100 µg/kg, and the average recoveries of the target pesticides in different matrices ranged from 76.4% to 123% with RSDs <12.2%. Finally, the method established was used to detect triazole pesticide residues in 30 actual Zhebawei samples. The results showed that triazole pesticides were present in Bulbus Fritillariae Thunbergii and Dendranthema Morifolium. Difenoconazole was detected in Bulbus Fritillariae Thunbergii at contents ranging from 41.4 µg/kg to 110 µg/kg, while difenoconazole, myclobutanil, triadimenol and propiconazole were detected in Dendranthema Morifolium at contents ranging from 16.1 µg/kg to 250 µg/kg. The established method can meet the requirements for the accurate quantitative analysis of triazole fungicides in Zhebawei.

Baicalein alleviates TNF-α-induced apoptosis of human nucleus pulposus cells through PI3K/AKT signaling pathway.

BACKGROUND: Nucleus pulposus (NP) cell apoptosis contributed to disc degeneration. Baicalein, a natural steroid saponin, has been demonstrated to have anti-inflammatory, antiapoptotic, and antioxidative effects in various diseases. However, little is known about the roles of baicalein in intervertebral disc degeneration. METHODS: To evaluate the roles of baicalein in disc degeneration and its specific mechanism, human NP cells were incubated with TNF-α and various concentrations of baicalein. Cell viability, extracellular matrix protein expression, catabolic factors, degree of apoptosis, inflammatory factors, and related signaling pathways were evaluated by western blotting, fluorescence immunostaining, TUNEL staining, and reverse transcription PCR. RESULTS: Baicalein inhibited TNF-α-activated apoptotic signaling and catabolic activity in NP cells. Baicalein promoted PI3K/Akt signaling and attenuated the level of apoptosis-related markers in TNF-α-stimulated human NP cells. CONCLUSION: Our work provides that baicalein attenuates TNF-α-activated apoptosis in human NP cells through promoting the PI3K/Akt pathway, indicating that baicalein is a new potential candidate for clinical therapy to attenuate disc degeneration.

Four-corners traction combined with continuous everting suture technique as a modification in bicaval anastomosis for orthotopic heart transplantation.

BACKGROUND: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. MATERIALS AND METHODS: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. RESULTS: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. CONCLUSIONS: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.

Comprehensive analysis of lncRNA-mediated ceRNA networkfor hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a high-burden cancer. The molecular mechanism of HCC has not been fully elucidated. Notably, current research has revealed a significant function for long non-coding RNAs (lncRNAs) in the prognosis of patients with HCC. Here, this study aims to construct a regulated lncRNA-mediated ceRNA network and find biological targets for the treatment of HCC. Methods: Based on the RNA expression patterns from the TCGA, we did an analysis to determine which genes were expressed differently between liver tumor tissues and noncancerous tissues. Then, using bioinformatic tools, we built a lncRNA-miRNA-mRNA ceRNA network and used GO and KEGG functional analyses on the DEmRNAs connected to ceRNA networks. The main lncRNAs in the subnetwork were chosen, and we next looked at the relationships between these lncRNAs and the clinical characteristics of patients with HCC. The prognosis-related genes and immune cells were identified using Kaplan-Meier and Cox proportional hazard analyses, and CIBERSORT was utilized to separate the 22 immune cell types. CCK8 assay was performed to measure cell viability in HCC cells after lncRNA HOTTIP modulation. Results: Differentially expressed mRNA and lncRNAs in HCC and paracancerous tissues were identified. There are 245 lncRNAs, 126 miRNAs, and 1980 mRNAs that are expressed differently in liver tumour tissues than in noncancerous cells. Function analysis showed that mRNAs in ceRNA network were significantly enriched in G1/S transition of mototiv cell cycle, positive regulation of cell cycle process, hepatocellular carcinoma, and cancer related pathways. CD8 T cells and T follicular helper cells had a favourable link with a 0.65 correlation coefficient. Additionally, there was a strong correlation between Eosinophils, activated NK cells, and B memory cells. Strikingly, depletion of lncRNA HOTTIP inhibited viability of HCC cells. In addition, miR-205 upregulation suppressed viability of HCC cells, while miR-205 downregulation repressed viability of HCC cells. Notably, miR-205 depletion rescued HOTTIP depletion-mediated suppression of cell viability in HCC. Conclusion: A ceRNA network was created by examining the lncRNA, miRNA, and mRNA expression profiles of liver tumours from the TCGA database. LncRNA HOTTIP promoted cell viability via inhibition of miR-205 in HCC cells.

Fbxo45 promotes the malignant development of esophageal squamous cell carcinoma by targeting GGNBP2 for ubiquitination and degradation.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers. Fbxo45, a substrate recognition subunit of E3 ligase, is critically involved in tumorigenesis and tumor progression. However, the function of Fbxo45 and the underlying mechanisms have not been elucidated in ESCC. We used cellular and molecular methods to explore the molecular basis of Fbxo45-mediated ESCC development. We found that ectopic overexpression of Fbxo45 promoted the growth of Kyse-150, Kyse30 and ECA-109 cells and inhibited the apoptosis. Moreover, overexpression of Fbxo45 promoted the migration and invasion of ESCC cells. Consistently, knockdown of Fbxo45 exhibited the opposite effects on ESCC cells. Mechanistically, we observed that Fbxo45 binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and degradation. GGNBP2 overexpression exhibited anticancer activity in ESCC cells. Furthermore, Fbxo45 exerted its functions by regulating GGNBP2 stability in ESCC cells. Notably, overexpression of Fbxo45 facilitated tumor growth in mice. Strikingly, Fbxo45 was highly expressed in ESCC tissues, and GGNBP2 had a lower expression in ESCC specimens. High expression of Fbxo45 and low expression of GGNBP2 were associated with poor prognosis in ESCC patients. Fbxo45 was negatively correlated with GGNBP2 expression in ESCC tissues. Therefore, Fbxo45 serves as an oncoprotein to promote ESCC tumorigenesis by targeting the stability of the tumor suppressor GGNBP2 in ESCC.

Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer.

Understanding the role of N6-adenosine methylation (m6A) in the tumor microenvironment (TME) is important since it can contribute to tumor development. However, the research investigating the association between m6A and TME and cervical cancer is still in its early stages. The aim of this study was to discover the possible relationship between m6A RNA methylation regulators, TME, PD-L1 expression levels, and immune infiltration in cervical cancer. We gathered RNA-seq transcriptome data and clinical information from cervical cancer patients using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. To begin, researchers assessed the differences in m6A regulatory factor expression levels between cervical cancer and normal tissues. Clustering analysis was adapted to assess PD-L1 expression, immunological score, immune cell infiltration, TME, and probable pathways in cervical cancer samples. The majority of m6A regulators were found to be considerably overexpressed in cervical cancer tissues. Using consensus clustering of 21 m6A regulators, we identified two subtypes (clusters 1/2) of cervical cancer, and we found that WHO stage and grade were associated with the subtypes. PD-L1 expression increased dramatically in cervical cancer tissues and was significantly linked to ALKBH5, FTO, METTL3, RBM15B, YTHDF1, YTHDF3, and ZC3H13 expression levels. Plasma cells and regulatory T cells (Tregs) were considerably elevated in cluster 2. Cluster 1 is involved in numerous signature pathways, including basal transcription factors, cell cycle, RNA degradation, and the spliceosome. The prognostic signature-based riskscore (METTL16, YTHDF1, and ZC3H13) was found to be an independent prognostic indicator of cervical cancer. The tumor immune microenvironment (TIME) was linked to m6A methylation regulators, and changes in their copy number will affect the quantity of tumor-infiltrating immune cells dynamically. Overall, our research discovered a powerful predictive signature based on m6A RNA methylation regulators. This signature correctly predicted the prognosis of cervical cancer patients. The m6A methylation regulator could be a critical mediator of PD-L1 expression and immune cell infiltration, and it could have a significant impact on the TIME of cervical cancer.

The functions of lncRNAs in the HPV-negative cervical cancer compared with HPV-positive cervical cancer.

Cervical cancer is one of the most common female malignancies. Human papillomaviruses (HPV) are the main causative agents of virtually all cervical carcinomas. Nevertheless, emerging evidence has demonstrated that a small proportion of cervical cancer patients are HPV negative. Long noncoding RNAs (lncRNAs) have been identified to play a crucial role in cervical cancer development. Here, this review describes the incidence and development of HPV-negative cervical cancer. Moreover, HPV-negative cervical cancers are more likely diagnosed at non-squamous type, older ages, more advanced stage and metastases, and associated with poorer prognosis as compared to HPV-positive cervical cancer. Furthermore, the significant role and functions of lncRNAs underlying HPV-negative cervical cancer is clarified.

Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells.

In the last decade, there has been a rapid expansion in tumor targeted therapy using mesenchymal stem cells (MSCs) based on their unique tropism towards cancer cells. Despite similarities in morphology, immunophenotype, and differential potent in vitro, MSCs originated from different tissues do not necessarily have equivalent biological behaviors. It is important to screen the most chemotactic MSCs to cancer cells. In this study, different MSCs were isolated from various human tissues including adipose, umbilical cord, amniotic membrane, and chorion. The chemotaxis of human MSCs to cervical cancer cells was measured by CCK-8, ELISA and Transwell invasion assays. Western blotting was performed to explore the underlying mechanisms. MSCs derived from distinct sources can be differently recruited to cervical cancer cells, among which chorion-derived MSC (CD-MSC) possessed the strongest tropic capacity. CXCL12 was found to be highly secreted by cervical cancer cells, in parallel with the expression of CXCR4 in all MSCs. CD-MSC displayed the highest level of CXCR4. These results indicated that CXCL12/CXCR4 pathway contributed to the different chemotaxis to cervical cancer cells of each MSCs. This study proposed that CD-MSC with the highest CXCR4 expression is a promising therapeutic vehicle for targeted therapy in cervical cancer.

Erratum: Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers.

[This corrects the article DOI: 10.1016/j.omto.2021.12.005.].

Unraveling diverse roles of noncoding RNAs in various human papillomavirus negative cancers.

Human papillomavirus (HPV)-negative tumors distinguish from cancers associated with HPV infection. Due to its high rate of lymph node metastasis and difficulty in inchoate discover and diagnosis, the treatment efficacy of HPV-negative cancers is unsatisfactory. Epidemiological evidence suggests that HPV-negative tumor patients have a poor prognosis, and the mortality is higher than that of cancer patients caused by HPV infection. Evidence has demonstrated that noncoding RNAs (ncRNAs) play a crucial role in regulation of physiological and developmental processes. Therefore, dysregulated ncRNAs are involved in the occurrence of diversified diseases, including cancer. In cumulative studies, ncRNAs are concerned with pathogenetic mechanisms of HPV-negative tumors via regulating gene expression and signal transduction. It is important to decipher the functions of ncRNAs in HPV-negative cancers and identify the potential biomarkers, which will bring new treatment strategies for improving outcome of cancer therapy. In this review, we demonstrated the effects of ncRNAs via regulating the development and progression of HPV- negative tumors by directly or indirectly acting on target molecules, which provide a basis for future tumor targeted therapy by targeting ncRNAs for HPV-negative cancers.