Design, Synthesis, and Biological Evaluation of 2-Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect.

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 µg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 µg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect.

Dehydroepiandrosterone with a high-fat diet treatment at inducing polycystic ovary syndrome in rat model.

OBJECTIVE: This study aimed to evaluate the effects of dehydroepiandrosterone (DHEA) and DHEA combined with a high-fat diet (HFD) treatment of reproductive and endocrine metabolism in rats and then identify an ideal model of polycystic ovary syndrome (PCOS). METHODS: Three-week-old female Sprague-Dawley rats were injected subcutaneously with DHEA or oil, fed with or without a HFD, for 21 days, during which body weight, feed intake, and estrous cycle monitoring were carried out. Fasting blood glucose was measured, and serum fasting insulin, testosterone, dihydrotestosterone (DHT), estradiol, progesterone, luteinizing hormone (LH), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were estimated by ELISA. Serum total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric assay. Whereas, histologic changes in rat ovaries were evaluated by H&E staining. Ovarian steroid hormone synthases and their protein levels (StAR, 3ß-HSD2, 17ß-HSD1, CYP11A1, CYP17A1, and CYP19A1) were examined by western blotting. RESULTS: Both DHEA and DHEA + HFD-treated rats loss of a regular estrous cycle; develop polycystic ovarian changes; significantly higher serum fasting insulin and testosterone levels; and increased ovarian StAR, 3ß-HSD2, and CYP11A1 protein levels. Additionally, rats in the DHEA + HFD-treated group were obese; had elevated fasting blood glucose, TG, DHT, AMH levels and LH:FSH ratios; increased ovarian 17ß-HSD1 protein levels. CONCLUSION: DHEA combined with HFD treatment is more effective at inducing PCOS than DHEA alone. The reproductive and endocrine metabolic aspects of this method are more consistent with the clinical characteristics of PCOS patients.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.

Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

A comprehensive analysis and experimental validation of TK1 in uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is becoming a main malignant cancer that threaten to women's health. Thymidine kinase 1 (TK1) is considering to be associated with tumorigenesis and development. Nevertheless, the function of TK1 in UCEC is still unclear. Herein, we analyzed the TK1 expression level in pan-cancer and found that TK1 was upregulated in a variety of cancers including UCEC. Patients of UCEC with high expression of TK1 were related to poor outcome. TK1 was also related to clinical stage, histologic grade and lymph node metastasis. Abnormal expression of TK1 in UCEC was related to promoter methylation while gene mutation was not frequent. TK1 and its associated genes appeared to be prominent in cell cycle and DNA replication, according to GO and KEGG analysis. Analysis of immune infiltration revealed a negative correlation between TK1 and CD8 + T cells, macrophages, and dendritic cells. In vitro experiments, TK1 knockdown resulted in the inhibition of proliferation, migration, invasion and EMT in UCEC cell lines.

Clear-cell papillary renal cell tumour: New insights into clinicopathological features and molecular landscape after renaming by 5th WHO classification.

OBJECTIVE: Clear cell papillary renal cell tumour (CCPRCT) is a kind of renal epithelial cell tumor, and was renamed by the 5th WHO due to its specific epidemiology and clinicopathological characteristics. However, the biological mechanism and molecular basis of CCPRCT still need to be further clarified. This study aims to comprehensively evaluate clinicopathologic and molecular characteristics of CCPRCC, and particularly compare it with other more prevalent subtypes of renal cell carcinoma. METHODS: 12 cases of CCPRCT were collected for analyzing the clinicopathological characteristics. Then, whole-exome sequencing (WES) was employed to reveal the genetic profiles, followed by comparison with the molecular genetic alterations identified in ccRCC (341) and pRCC (200) datasets obtained from the TCGA database. RESULTS: Of the 12 CCPRCT cases, the male-to-female ratio was 4:1 with a mean age of 49.5 years (48.5 ± 10.5) at diagnosis. All patients were diagnosed accidentally during routine physical examinations. All tumors (12/12, 100%）had a solid-cystic appearance with a well-defined fibrous capsule. The median size of the tumors was 3 cm (2.98 ± 1.2). Histologically, the cystic papillary structures were considered to be prominent, lined with cuboidal tumor cells away from basement membrane. The tumor cells were moderately atypia equivalent to grade 1 or grade 2 according to the ISUP nuclear grading system. Typically, the tumor cell diffusely positive for CK7 and CAIX in a "cup-like" pattern. The results of WES revealed recurrent gene alterations (mainly missense mutation) of TTN and FLT in 4 cases (4/12, 33.3%), respectively, of which, the alteration of FLT was not observed in ccRCC and pRCC of the TCGA database. Other gene alterations including POTEC (1 cases), PRADC1 (1 cases), ZZZ3 (1 case) and PTPRZ1 (1 case), etc. Moreover, all of the CCPRCT cases displayed a lower tumor mutation burden (TMB) compared to ccRCC and pRCC with median TMB of 1.04 (range: 1.94 ± 2.74). None of the patients experienced tumor metastasis, recurrence, or tumor-related deaths. CONCLUSION: CCPRCT is a renal epithelial cell tumor characterized by specific clinical and pathological features. Our study provides additional evidence supporting the favorable prognosis of CCPRCT. Furthermore, the potential molecular alterations were uncovered by this study in CCPRCT such as the FLT family and TTN. However, due to the limited sample size, larger studies are required to validate these findings.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

Liproxstatin-1 alleviates ferroptosis in sevoflurane anesthesia-induced cognitive deficits of aged mice: The role oxidative stress.

In this study, we aimed to validate the hypothesis that the interplay between sevoflurane, oxidative stress and ferroptosis is crucial for the pathogenesis of sevoflurane-induced cognitive impairment in aged individuals. The mice with sevoflurane-induced cognitive impairment were used to explore the effects of sevoflurane on oxidative stress, iron homeostasis, and cognitive function in aged mice. Iron content and oxidative stress markers were analyzed in hippocampal tissue homogenates using specific assays. Additionally, the levels of iron death-related markers (Fth1 and Gpx4) were assessed by real-time PCR and Western blotting. Morris Water Maze and novel object recognition (NOR) tests were conducted to evaluate cognitive function. Sevoflurane exposure in aged mice resulted in a significant increase in iron overloading in the hippocampus, followed by a subsequent stabilization. Oxidative stress levels were elevated in the hippocampal tissue of sevoflurane-exposed mice, and a significant correlation was observed between iron death and oxidative stress. Liproxstatin-1, a ferroptosis inhibitor, effectively ameliorated the decline in memory and learning abilities induced by sevoflurane anesthesia. Liproxstatin-1 treatment reduced iron overload and oxidative stress in the hippocampal tissue of aged mice. The expression of Fth1 and Gpx4, iron death-related markers, was downregulated following Liproxstatin-1 intervention. Our findings suggest that sevoflurane anesthesia disrupts iron homeostasis, leading to increased oxidative stress and cognitive impairment in aged mice. These results highlight the potential of targeting iron-mediated processes to mitigate sevoflurane-induced cognitive impairment in the aging population.

Ginsenoside 20(S)-Rg3 reduces KIF20A expression and promotes CDC25A proteasomal degradation in epithelial ovarian cancer.

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-κB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (ß-TrCP1), a substrate recognition subunit for SCFß-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.

Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.

Avoiding unnecessary biopsy: the combination of PRIMARY score with prostate-specific antigen density for prostate biopsy decision.

BACKGROUND: Avoiding unnecessary biopsies for men with suspected prostate cancer remains a clinical priority. The recently proposed PRIMARY score improves diagnostic accuracy in detecting clinically significant prostate cancer (csPCa). The aim of this study was to determine the best strategy combining PRIMARY score or MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]) with prostate-specific antigen density (PSAD) for prostate biopsy decision making. METHODS: A retrospective analysis of 343 patients who underwent both 68Ga-PSMA PET/CT and MRI before prostate biopsy was performed. PSA was restricted to <20 ng/ml. Different biopsy strategies were developed and compared based on PRIMARY score or PI-RADS with PSAD thresholds. Decision curve analysis (DCA) was plotted to define the optimal biopsy strategy. RESULTS: The prevalence of csPCa was 41.1% (141/343). According to DCA, the strategies of PRIMARY score +PSAD (strategy #1, strategy #2, strategy #6) had a higher net benefit than the strategies of PI-RADS + PSAD at the risk threshold of 8-20%. The best diagnostic strategy was strategy #1 (PRIMARY score 4-5 or PSAD ≥ 0.20), which avoided 38.2% biopsy procedures while missed 9.2% of csPCa cases. From a clinical perspective, strategies with a lower risk of missing csPCa were strategy #2 (PRIMARY score ≥4 or PSAD ≥ 0.15), which avoided 28.6% biopsies while missed 5.7% of csPCa cases, or strategy #6 (PRIMARY score≥3 or PSAD ≥ 0.15), which avoided 20.7% biopsies while missed only 3.5% of csPCa cases. The limitations of the study were the retrospective single-center nature. CONCLUSIONS: The combination of PRIMARY score +PSAD allows individualized decisions to avoid unnecessary biopsy, outperforming the strategies of PI-RADS + PSAD. Further prospective trials are needed to validate these findings.

Comprehensive Analysis Reveals the Potential Roles of CDKN3 in Pancancer and Verification in Endometrial Cancer.

Background: Cyclin-dependent kinase inhibitor 3 (CDKN3) has been studied in many cancers. However, the comprehensive and systematic pancancer analysis of CDKN3 genes is still lacking. Methods: Data were downloaded from online databases. R was used for analysis of the differential expression and gene alteration of CDKN3 and of the associations between CDKN3 expression and survival, signaling pathways, and drug sensitivity. Clinical samples and in vitro experiments were selected for verification. Results: CDKN3 expression was higher in most types of cancers, and this phenotype was significantly correlated with poor survival. CDKN3 showed gene alterations and copy number alterations in many cancers and associated with some immune-related pathways and factors. Drug sensitivity analysis elucidated that CDKN3 could be a useful marker for therapy selection. Clinical samples elucidated CDKN3 expressed high in endometrial cancer tissue. In vitro studies showed that CDKN3 induced pro-tumor effect in immune environment and facilitated endometrial cancer cell proliferation and G1/S phase transition. Conclusion: CDKN3 has been shown to be highly expressed in most types of cancers and promoted cancer cell progression. CDKN3 may serve as a novel marker in clinical diagnosis, treatment, and prognosis prediction in future.

A CRISPR-Cas9 library screening identifies CARM1 as a critical inhibitor of ferroptosis in hepatocellular carcinoma cells.

Ferroptosis is an iron-catalyzed form of regulated cell death that results from the accumulation of lipid peroxidation products and reactive oxygen species to a lethal content. However, the transcriptional regulation of ferroptosis is not well understood. Sorafenib, a standard drug for hepatocellular carcinoma (HCC), induces ferroptosis in HCC cells. In this study, we conducted a CRISPR-Cas9 library screening targeting epigenetic factors and identified coactivator-associated arginine methyltransferase 1 (CARM1) as a critical inhibitor of ferroptosis. CARM1 depletion intensified Sorafenib-induced ferroptosis, resulting in decreased cell viability, reduced cellular glutathione level, increased lipid peroxidation, and altered mitochondrial crista structure. Additionally, we investigated a CARM1 inhibitor (CARM1i) as a potential ferroptosis inducer. Combining the CARM1i with Sorafenib enhanced the induction of ferroptosis. Notably, both CARM1 knockdown and CARM1i showed cooperative effects with Sorafenib in inhibiting HCC growth in mice. The underlying mechanism involves CARM1-catalyzed H3R26me2a on the promoter of glutathione peroxidase 4, leading to its transcriptional activation and subsequent ferroptosis inhibition. Furthermore, Sorafenib treatment induced the transcription of CARM1 through the MDM2-p53 axis. In summary, our findings establish CARM1 as a critical ferroptosis inhibitor and highlight the potential of CARM1is as novel ferroptosis inducers, providing promising therapeutic strategies for HCC treatment.

The Hippo pathway in endometrial cancer: a potential therapeutic target?

Endometrial cancer, one of the most prevalent malignant cancers tumors of the female reproductive tract, has been increasing in incidence and mortality rates around the world. The Hippo pathway, one of the eight traditional human cancer signaling pathways, is an intricate signaling network that regulates cell proliferation, differentiation, and migration as well as restricting organ size in response to a range of intracellular and extracellular signals. Inhibiting the Hippo pathway results in aberrant activation of its downstream core component YAP/TAZ, which can enhance cancer cells' metabolism and maintain their stemness. Additionally, the Hippo pathway can modulate the tumor microenvironment and induce drug resistance, where tumorigenesis and tumor progression occur. However, the Hippo pathway has been little researched in endometrial cancer. Here, we aim to review how the Hippo pathway contributes to the onset, development and the potential treatment of endometrial cancer with the aim of providing new therapeutic targets.

Compound AC1Q3QWB upregulates CDKN1A and SOX17 by interrupting the HOTAIR-EZH2 interaction and enhances the efficacy of tazemetostat in endometrial cancer.

Endometrial cancer (EC) is a common malignancy of the female reproductive system, with an escalating incidence. Recurrent/metastatic EC presents a poor prognosis. The interaction between the long non-coding RNA (lncRNA) HOTAIR and the polycomb repressive complex 2 (PRC2) induces abnormal silencing of tumor suppressor genes, exerting a pivotal role in tumorigenesis. We have previously discovered AC1Q3QWB (AQB), a small-molecule compound targeting HOTAIR-EZH2 interaction. In the present study, we unveil that AQB selectively hampers the interaction between HOTAIR and EZH2 within EC cells, thus reversing the epigenetic suppression of tumor suppressor genes. Furthermore, our findings demonstrate AQB's synergistic effect with tazemetostat (TAZ), an EZH2 inhibitor, significantly boosting the expression of CDKN1A and SOX17. This, in turn, induces cell cycle arrest and impedes EC cell proliferation, migration, and invasion. In vivo experiments further validate AQB's potential by enhancing TAZ's anti-tumor efficacy at lower doses. Our results advocate AQB, a recently discovered small-molecule inhibitor, as a promising agent against EC cells. When combined with TAZ, it offers a novel therapeutic strategy for EC treatment.

Comprehensive analyses of fatty acid metabolism-related lncRNA for ovarian cancer patients.

Ovarian cancer (OC) is a disease with difficult early diagnosis and treatment and poor prognosis. OC data profiles were downloaded from The Cancer Genome Atlas. Eight key fatty acid metabolism-related long non-coding RNAs (lncRNAs) were finally screened for building a risk scoring model by univariate/ multifactor and least absolute shrinkage and selection operator (LASSO) Cox regression. To make this risk scoring model more applicable to clinical work, we established a nomogram containing the clinical characteristics of OC patients after confirming that the model has good reliability and validity and the ability to distinguish patient prognosis. To further explore how these key lncRNAs are involved in OC progression, we explored their relationship with LUAD immune signatures and tumor drug resistance. The structure shows that the risk scoring model established based on these 8 fatty acid metabolism-related lncRNAs has good reliability and validity and can better predict the prognosis of patients with different risks of OC, and LINC00861in these key RNAs may be a hub gene that affects the progression of OC and closely related to the sensitivity of current OC chemotherapy drugs. In addition, combined with immune signature analysis, we found that patients in the high-risk group are in a state of immunosuppression, and Tfh cells may play an important role in it. We innovatively established a prognostic prediction model with excellent reliability and validity from the perspective of OC fatty acid metabolism reprogramming and lncRNA regulation and found new molecular/cellular targets for future OC treatment.

Impact of timing on protection of combined immunoprophylaxis in preventing mother-to-child transmission of hepatitis B virus: a retrospective study.

Objective: To evaluate the impact of timing combined immunoprophylaxis on mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) in pregnant women living with hepatitis B. Methods: A retrospective cohort study was included HBsAg-positive pregnant women who delivered full-term at Tianjin Third Central Hospital from January 2019 to December 2021. The objective of this study is to determine whether early administration of hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccination after birth can further improve protection. Result: A total of 694 pregnant women living with hepatitis B were included; 93 infants from these mothers were lost to follow-up [including moving (n = 21), emigrating (n = 26), changing contact information (n = 27), and other reasons (n = 19)], leaving 601 infants for analysis. The incidence in babies born to mothers with hepatitis B was 1.50% (9/601). Based on the different timing of combined immunoprophylaxis administration after birth, 601 infants were divided into two groups (within 2 h and within 2-12 h). The incidence in babies born to mothers with hepatitis B were 0.32% (1/308) and 2.73% (8/293) for infants who received combined immunoprophylaxis within 2 h and between 2 and 12 h of birth, respectively (p = 0.037). The infection incidence of infants born to HBeAg-positive mothers and HBeAg-positive mothers who did not receive antiviral treatment during pregnancy was lower in the 2-h group compared to the 2-12 h group (0.72% vs. 5.84%, p = 0.04 and 1.20% vs. 9.46%, p = 0.047). Conclusion: Using combined immunoprophylaxis as soon as possible (within two hours of birth) may protect against MTCT of HBV more.

E7 as a Promising Biomarker for Monitoring the Progression of Cervical Lesions in Patients with HPV 16/18 Infections.

Objective: To investigate the expression of E7 protein and its relationship with the progression and prognosis of cervical pre-cancerous lesions in patients with human papillomavirus (HPV) 16/18 infections. Methods: A total of 211 patients with positive HPV 16/18 were included in this study. Patients were categorized into three groups based on colposcopy results: NILM (Negative for Intraepithelial Lesion or Malignancy), LSIL (Low-Grade Squamous Intraepithelial Lesion), and HSIL (High-Grade Squamous Intraepithelial Lesion). E7 protein levels were quantified using Immunochromatographic Assay and compared using ANOVA. Cervical E7 protein levels were assessed before and one year after cervical cone biopsy in the HSIL group. Results: Among HPV 16/18-positive patients with normal Cervical Thinprep Cytologic Test (TCT) results, E7 protein content exhibited abnormal and significant values (P = .001). Mean E7 protein levels for the NILM, LSIL, and HSIL groups were 44.52 ng/mL, 114.60 ng/mL, and 389.20 ng/mL, respectively, and showed statistical significance (P = .000). In the HSIL group, E7 protein levels in HPV-negative patients were significantly lower one year after cervical cone biopsy compared to before (P = .001). However, HPV-positive patients displayed no significant alteration in E7 protein levels before and after biopsy (P = .08). Conclusions: E7 protein levels in detached cervical cells are closely associated with the severity and prognosis of cervical pre-cancerous lesions, suggesting their potential role as a biomarker for monitoring cervical lesion development.

Cytoplasmic SIRT1 promotes paclitaxel resistance in ovarian carcinoma through increased formation and survival of polyploid giant cancer cells.

Therapeutic resistance is a notable cause of death in patients with ovarian carcinoma. Polyploid giant cancer cells (PGCCs), commonly arising in tumor tissues following chemotherapy, have recently been considered to contribute to drug resistance. As a type III deacetylase, Sirtuin1 (SIRT1) plays essential roles in the cell cycle, cellular senescence, and drug resistance. Accumulating evidence has suggested that alteration in its subcellular localization via nucleocytoplasmic shuttling is a critical process influencing the functions of SIRT1. However, the roles of SIRT1 subcellular localization in PGCC formation and subsequent senescence escape remain unclear. In this study, we compared the differences in the polyploid cell population and senescence state of PGCCs following paclitaxel treatment between tumor cells overexpressing wild-type SIRT1 (WT SIRT1) and those expressing nuclear localization sequence (NLS)-mutated SIRT1 (SIRT1NLSmt ). We investigated the involvement of cytoplasmic SIRT1 in biological processes and signaling pathways, including the cell cycle and cellular senescence, in ovarian carcinoma cells' response to paclitaxel treatment. We found that the SIRT1NLSmt tumor cell population contained more polyploid cells and fewer senescent PGCCs than the SIRT1-overexpressing tumor cell population. Comparative proteomic analyses using co-immunoprecipitation (Co-IP) combined with liquid chromatography-mass spectrometry (LC-MS)/MS showed the differences in the differentially expressed proteins related to PGCC formation, cell growth, and death, including CDK1 and CDK2, between SIRT1NLSmt and SIRT1 cells or PGCCs. Our results suggested that ovarian carcinoma cells utilize polyploidy formation as a survival mechanism during exposure to paclitaxel-based treatment via the effect of cytoplasmic SIRT1 on PGCC formation and survival, thereby boosting paclitaxel resistance. © 2023 The Pathological Society of Great Britain and Ireland.