ABSTRACT
Background: This study aimed to determine the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), prognostic nutritional index (PNI), fibrinogen-to-albumin ratio (FAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the combination of the six inflammatory-nutritional markers for ovarian cancer (OC) to identify the best diagnostic indicator for OC early diagnosis. An extensive study was performed to establish the connection between these indicators and the pathological aspects of OC. Methods: A total of 170 individuals were included in this study, with 87 diagnosed with OC and 83 with benign ovarian tumors (BOTs). The diagnostic abilities of the variables were evaluated by calculating sensitivity, specificity, and area under the ROC curves. Through the use of DCA, we evaluated the variables' clinical value in the discrimination of ovarian masses. Results: All markers showed significant diagnostic power for OC. CA125, HE4, SII, FAR, and MLR levels significantly increased from the BOTs group to the early-stage OC group. The advanced-stage OC group had significantly lower PNI values compared to the early-stage OC group but significantly higher levels of CA125, HE4, SII, NLR, and FAR. Moreover, the OC group with lymph node metastasis exhibited significantly higher levels of CA125, HE4, SII, NLR, PLR, and FAR, in contrast to the non-metastatic group, while PNI levels were significantly lower. Categorical factors, such as histological grade and pathological classification, showed noticeable discrepancies in CA125 and HE4 levels. NLR was significantly different among the pathological type groups. Among the six inflammatory-nutritional markers, the FAR displayed the greatest diagnostic value. In the analysis of logistic regression, it was observed that a combination marker containing all six inflammatory-nutritional markers exhibited a notably higher AUC value (0.881; 95% CI, 0.823 - 0.926) than any of the individual marker. Conclusion: PNI, NLR, PLR, MLR, SII, and FAR showed excellent diagnostic performance for OC. The combination of these markers demonstrated a superior diagnostic capability compared to each individual one. The systemic inflammatory indicators may be helpful to diagnose OC.
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Crystal facet and defect engineering are crucial for designing heterogeneous catalysts. In this study, different solvents were utilized to generate NiO with distinct shapes (hexagonal layers, rods, and spheres) using nickel-based metal-organic frameworks (MOFs) as precursors. It was shown that the exposed crystal facets of NiO with different morphologies differed from each other. Various characterization techniques and density functional theory (DFT) calculations revealed that hexagonal-layered NiO (NiO-L) possessed excellent low-temperature reducibility and oxygen migration ability. The (111) crystal plane of NiO-L contained more lattice defects and oxygen vacancies, resulting in enhanced propane oxidation due to its highest O2 adsorption energy. Furthermore, the higher the surface active oxygen species and surface oxygen vacancy concentrations, the lower the C-H activation energy of the NiO catalyst and hence the better the catalytic activity for the oxidation of propane. Consequently, NiO-L exhibited remarkable catalytic activity and good stability for propane oxidation. This study provided a simple strategy for controlling NiO crystal facets, and demonstrated that the oxygen defects could be more easily formed on NiO(111) facets, thus would be beneficial for the activation of C-H bonds in propane. In addition, the results of this work can be extended to the other fields, such as propane oxidation to propene, fuel cells, and photocatalysis.
ABSTRACT
BACKGROUND: Low grade serous carcinoma of the ovary (LGSOC) is a rare type of epithelial ovarian cancer with a low incidence rate. The origin of ovarian cancer has always been a hot topic in gynecological oncology research, and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes. Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system. There are only a few reports in the literature, but the mortality rate is very high. But in clinical practice, fallopian tube cancer is very common, but in most cases, it is classified as ovarian cancer. CASE SUMMARY: We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment. The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube. No special treatment was performed after the surgery, and the patient was instructed to undergo regular follow-up without any signs of disease progression. CONCLUSION: The prognosis of LGSOC is relatively good, over 80% of patients still experience disease recurrence.
ABSTRACT
Objective: To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods: First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor ß, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results: APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.
Subject(s)
Ferroptosis , Panax notoginseng , Pulmonary Fibrosis , Animals , Mice , Pulmonary Fibrosis/drug therapy , Cyclooxygenase 2 , Collagen , ErbB ReceptorsABSTRACT
BACKGROUND: The balance of vaginal microecology is closely related to human papillomavirus (HPV) infection and cervical lesions. This study aims to investigate the relationship between bacterial vaginosis (BV) and HPV infection. METHODS: In total, 1,310 individuals from the National Health and Nutrition Examination Survey (NHANES, 2003-2004) were included in this study. Logistic regression and subgroup analyses were used to examine the association between BV and HPV infection. RESULTS: A significant positive association was observed between BV and HPV infection in women after adjustment for other confounders (OR = 1.47, 95% confidence interval [CI]: 1.15-1.88). In subgroup analyses, we have found this positive correlation was most prominent among Mexican Americans (OR = 1.83, 95% CI: 1.08-3.08) and non-Hispanic blacks (OR = 1.81, 95% CI: 1.08-3.04). CONCLUSIONS: This cross-sectional study demonstrated a positive association between BV and HPV infection in women.
Subject(s)
Papillomavirus Infections , Vaginosis, Bacterial , Female , Humans , United States/epidemiology , Vaginosis, Bacterial/epidemiology , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Papillomavirus Infections/diagnosis , Human Papillomavirus Viruses , Nutrition Surveys , Cross-Sectional StudiesABSTRACT
Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.
Subject(s)
Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/drug therapy , Lipid Peroxidation , Oxidative Stress , Alveolar Epithelial Cells , IronABSTRACT
Parkinson's disease (PD) is a central nervous system disease with the highest disability and mortality rate worldwide, and it is caused by a variety of factors. The most common medications for PD have side effects with limited therapeutic outcomes. Many studies have reported that chitosan oligosaccharide (COS) crossed blood-brain barrier to achieve a neuroprotective effect in PD. However, the role of COS in PD remains unclear. The present study demonstrated that COS increased dopaminergic neurons in the substantia nigra (SN) and ameliorated dyskinesia in a PD mouse model. Moreover, COS reduced gut microbial diversity and faecal short-chain fatty acids. Valeric acid supplementation enhanced the inflammatory response in the colon and SN, and it reversed COS - suppressed dopamine neurons damage. Autophagy was involved in COS modulating inflammation through valeric acid. These results suggest that COS reduces bacterial metabolites - valeric acid, which diminishes inflammation via activating autophagy, ultimately alleviating PD.
Subject(s)
Chitosan , Neuroprotective Agents , Parkinson Disease , Pentanoic Acids , Animals , Mice , Parkinson Disease/drug therapy , Chitosan/pharmacology , Neuroprotective Agents/pharmacology , Autophagy , Inflammation/drug therapy , Oligosaccharides/pharmacology , Oligosaccharides/therapeutic use , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
BACKGROUND: Viral diseases continue to pose a major threat to the world's commercial crops. The in-depth exploration and efficient utilization of resistance proteins have become crucial strategies for their control. However, current delivery methods for introducing foreign DNA suffer from host range limitations, low transformation efficiencies, tissue damage, or unavoidable DNA integration into the host genome. The nanocarriers provides a convenient channel for the DNA delivery and functional utilization of disease-resistant proteins. RESULTS: In this research, we identified a cysteine-rich venom protein (NbCRVP) in Nicotiana benthamiana for the first time. Virus-induced gene silencing and transient overexpression clarified that NbCRVP could inhibit the infection of tobacco mosaic virus, potato virus Y, and cucumber mosaic virus, making it a broad-spectrum antiviral protein. Yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation revealed that calcium-dependent lipid-binding (CaLB domain) family protein (NbCalB) interacted with NbCRVP to assist NbCRVP playing a stronger antiviral effect. Here, we demonstrated for the first time the efficient co-delivery of DNA expressing NbCRVP and NbCalB into plants using poly(amidoamine) (PAMAM) nanocarriers, achieving stronger broad-spectrum antiviral effects. CONCLUSIONS: Our work presents a tool for species-independent transfer of two interacting protein DNA into plant cells in a specific ratio for enhanced antiviral effect without transgenic integration, which further demonstrated new strategies for nanocarrier-mediated DNA delivery of disease-resistant proteins.
Subject(s)
Nicotiana , RNA Viruses , Nicotiana/genetics , Calcium , DNA , Antiviral Agents/pharmacologyABSTRACT
BACKGROUND AND PURPOSE: Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR-dependent autophagy. EXPERIMENTAL APPROACH: The symptoms of dextran sulfate sodium (DSS)-induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild-type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS-induced AhRs and autophagic Becn1 was investigated using a dual-luciferase reporter system and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction assay. Caco-2 cells were used to investigate inflammatory responses and AhR-dependent autophagy. KEY RESULTS: APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS. CONCLUSIONS AND IMPLICATIONS: APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.
Subject(s)
Colitis , Receptors, Aryl Hydrocarbon , Animals , Humans , Mice , Autophagy , Caco-2 Cells , Colitis/chemically induced , Colitis/drug therapy , Colitis/prevention & control , Dextran Sulfate , Disease Models, Animal , Inflammation , Mice, Inbred C57BL , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Receptors, Aryl Hydrocarbon/geneticsABSTRACT
INTRODUCTION: Primary vaginal malignant melanoma is a rare gynecological malignant tumor with high malignancy and poor prognosis. Because of its insidious incidence, it is generally diagnosed in the late stage, and the 5-year survival rate is only 5% to 25%. Due to the rarity of this disease and the limited number of related cases reported in the literature, there is currently no unified standard for its diagnosis and treatment. Therefore, the treatment of this disease has always been a difficult problem in clinical practice. PATIENT CONCERNS: A 56-year-old woman was admitted to our hospital with discomfort in the lower abdomen. DIAGNOSIS: The final diagnosis of this patient was vaginal malignant melanoma (T4N1M0). INTERVENTIONS: The patient underwent extensive hysterectomy, bilateral adnexectomy, pelvic lymph node resection, and total vaginectomy. Following the surgery, the patient received adjuvant chemotherapy. OUTCOMES: The patient was followed up regularly. No recurrence or metastasis has been reported to date. CONCLUSION: The treatment of primary vaginal malignant melanoma is still dominated by surgery, while radiotherapy and chemotherapy are controversial. Immunotherapy and targeted therapy highlight certain advantages in advanced patients, which still need to be verified by large sample studies, We provide a case of postoperative adjuvant chemotherapy for vaginal malignant melanoma. So far, no signs of disease recurrence have been found. As the price of chemotherapy drugs decreases, it is economically convenient and acceptable for most patients, but its effectiveness needs to be observed in large-scale clinical trials.
Subject(s)
Melanoma , Vaginal Neoplasms , Female , Humans , Middle Aged , Lymph Node Excision , Lymph Nodes/pathology , Melanoma/diagnosis , Melanoma/surgery , Neoplasm Recurrence, Local/surgery , Vaginal Neoplasms/surgery , Vaginal Neoplasms/pathologyABSTRACT
The concept of enhanced recovery after surgery (ERAS) was first proposed by Professor Kehlet from the University of Copenhagen in Denmark in 1997. The aim is to optimize multiple perioperative management measures, promote rapid postoperative recovery, shorten hospital stay, and reduce surgical related costs, this article explores the effect of optimizing perioperative bowel preparation and diet management under the strategy of ERAS on the postoperative recovery of patients undergoing laparoscopic hysterectomy for benign gynecological diseases. We selected 90 patients who underwent laparoscopic total hysterectomy for benign gynecological diseases at Hebei General Hospital from June 2018 to June 2019, these patients are between the ages of 40 and 65. Divide these 90 patients into an experimental group and a control group using a random number table method (nâ =â 45). The experimental group of patients applied the concept of accelerated rehabilitation surgery for perioperative intestinal preparation and dietary management. The control group patients received routine perioperative management. Compare the first postoperative exhaust time, first postoperative defecation time, incision healing status 7 days after surgery, and pelvic infection status 1 month after surgery between 2 groups of patients. The first postoperative exhaust time and first postoperative bowel movement time of the experimental group patients were shorter than those of the control group (Pâ <â .05), and the difference was statistically significant; The incidence of poor incision healing 7 days after surgery was lower than that of the control group (Pâ <â .05), and the difference was statistically significant; There was no statistically significant difference in the incidence of postoperative pelvic infection between the experimental group and the control group (Pâ >â .05). Perioperative intestinal preparation and dietary management under the concept of accelerated rehabilitation surgery can promote postoperative recovery of patients undergoing laparoscopic total hysterectomy, promote incision healing, and have good safety.
Subject(s)
Laparoscopy , Pelvic Infection , Female , Humans , Adult , Middle Aged , Aged , Laparoscopy/methods , Perioperative Care/methods , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Length of Stay , Hysterectomy/adverse effectsABSTRACT
Purpose: The relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs. Methods: In this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility. Results: PCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p<0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p<0.05), but had no statistical impact on patients with oligomenorrhea. Conclusion: The findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea.
Subject(s)
Coronary Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Infertility , Menorrhagia , Polycystic Ovary Syndrome , Humans , Female , Proprotein Convertase 9/genetics , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/chemically induced , Genome-Wide Association Study , Mendelian Randomization Analysis , Menorrhagia/chemically induced , Oligomenorrhea , PCSK9 Inhibitors , Hypolipidemic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Lipids , Infertility/chemically inducedABSTRACT
Saccharomyces cerevisiae has emerged as a preferred source for industrial production of ribonucleic acids (RNAs) and their derivatives, which find wide applications in the food and pharmaceutical sectors. In this study, we employed a modified RNA polymerase I-mediated green fluorescent protein expression system, previously developed by our team, to screen and identify an industrial S. cerevisiae strain with an impressive 18.2% increase in the RNA content. Transcriptome analysis revealed heightened activity of genes and pathways associated with rRNA transcription, purine metabolism, and phosphate transport in the high nucleic acid content mutant strains. Our findings highlighted the crucial role of the transcription factor Sfp1p in enhancing the expression of two key components of the transcription initiation factor complex, Rrn7p and Rrn11p, thereby promoting rRNA synthesis. Moreover, elevated expression of 5'-inosine monophosphate dehydrogenases, regardless of the specific isoform (IMD2, 3, or 4), resulted in increased rRNA synthesis through heightened GTP levels. Additionally, exogenous phosphate application, coupled with overexpression of the phosphate transporter PHO84, led to a 61.4% boost in the RNA yield, reaching 2050.4 mg/L. This comprehensive study provides valuable insights into the mechanism of RNA synthesis and serves as a reference for augmenting RNA production in the food industry.
Subject(s)
Nucleic Acids , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , RNA/metabolism , Phosphates/metabolism , Nucleic Acids/metabolismABSTRACT
This study aimed to ascertain the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), fibrinogen-to-albumin ratio (FAR), prognostic nutritional index (PNI), and their combination for ovarian cancer (OC) to discover an optimal combined diagnostic index for early diagnosis of OC. A thorough investigation was conducted to ascertain the correlation between these markers and the pathological characteristics of OC, thereby providing a foundation for early identification and treatment of this disorder. One hundred seventy patients with documented OC and benign ovarian tumors (BOTs) treated at Hebei General Hospital between January 2019 and December 2022 were included in this retrospective study. Data analysis was conducted using IBM SPSS Statistics version V26.0, MedCalc Statistical Software version 19.4.0, and the R Environment for Statistical Computing software (R Foundation for Statistical Computing). Isolated CA125 showed the best application value for differentiating benign ovarian tumors from OC when the defined variables were compared separately. The combination of CA125, HE4, FAR, SII, and PNI displayed a greater area under the operating characteristic curve curve than any one of them or other combinations of the 5 variables. Compared to CA125 alone, the combination of CA125, HE4, FAR, SII, and PNI showed a slight gain in sensitivity (83.91%), negative predictive value (83.91%), accuracy (85.88%), and a decrease in negative likelihood ratio (0.180%). Higher preoperative CA125, HE4, SII, and FAR levels, and lower PNI levels predicted a higher probability of advanced OC progression and lymph node metastasis. FAR has better application value than other inflammation-related markers (PNI and SII). This study suggests that preoperative serum SII, PNI, and FAR may be clinically valuable markers in patients with OC. FAR has better application value than other inflammation-related markers (PNI and SII). As we delve deeper into the inflammatory mechanisms associated with tumors, we may discover more effective combinations of tumor and inflammatory biomarkers.
Subject(s)
Ovarian Neoplasms , Female , Humans , CA-125 Antigen , Carcinoma, Ovarian Epithelial , Inflammation/diagnosis , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Retrospective StudiesABSTRACT
BACKGROUND: To systematically analyze the value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial cancer, so as to provide evidence-based medical evidence for the selection of serum tumor markers in the early screening of endometrial cancer. METHODS: We comprehensively searched relevant literature in the Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, VIP, WanFang, and CBM from the date of establishment to November 31, 2021. Quality assessment of diagnostic accuracy studies 2 was applied to evaluate the quality of the included literature. We used Stata 16.0 to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and plot summary receiver operating characteristic curve, as well as to assess diagnostic accuracy using the area under the curve (AUC). RESULTS: A total of 25 studies, including 1980 patients and 2345 controls, were included in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 were 0.58 (95% CI 0.52-0.63), 0.95 (95% CI 0.92-0.97), 11.57 (95% CI 6.88-19.48), 0.45 (95% CI 0.39-0.51), 25.92 (95% CI 14.84-45.26), and 0.80 (95% CI 0.76-0.83), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of CA125 were 0.41 (95% CI 0.34-0.49), 0.91 (95% CI 0.85-0.95), 4.55 (95% CI 2.73-7.58), 0.65 (95% CI 0.57-0.74), 7.03 (95% CI 3.92-12.62), and 0.68 (95% CI 0.64-0.72), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4â +â CA125 were 0.67 (95% CI 0.60-0.73), 0.92 (95% CI 0.87-0.95), 8.59 (95% CI 5.32-13.86), 0.36 (95% CI 0.30-0.44), 23.80 (95% CI 13.86-40.86), and 0.85 (95% CI 0.82-0.88), respectively. CONCLUSION: This Meta-analysis found that HE4 alone or in combination with CA125 showed better diagnostic efficacy than CA125, regardless of clinical stage and pathological type. HE4â +â CA125 had slightly higher diagnostic efficiency than HE4, but did not show significant advantages. While the studies were heterogeneous, the credibility of the findings needs to be further confirmed by more homogeneous, prospective, and large sample size studies.
Subject(s)
Endometrial Neoplasms , Female , Humans , Area Under Curve , Biomarkers, Tumor , CA-125 Antigen , Carbohydrates , Endometrial Neoplasms/diagnosis , Prospective StudiesABSTRACT
RATIONALE: Primary squamous cell carcinoma of the endometrium (PSCCE) has been occasionally reported. Treatment of this disease poses a challenge to clinicians because of its rarity. Herein, we report the case of a 56-year-old woman with typical clinical manifestations and a pathological diagnosis classified by molecular typing as having high microsatellite instability (MSI-H) PSCCE. Based on a review of the previous literature, we summarized the treatment options for this rare disease and proposed new opinions. PATIENT CONCERNS: A 56-year-old woman was admitted to our hospital with irregular vaginal bleeding and lower abdominal swelling. DIAGNOSIS: The patient was diagnosed with squamous cell carcinoma of the endometrium (stage IIIC1; MSI-H). INTERVENTIONS: The patient underwent total abdominal hysterectomy, bilateral salpingo-ovariectomy (bso), and pelvic lymph node dissection. Following the surgery, the patient received adjuvant chemoradiotherapy. OUTCOMES: The patient was followed up regularly. No recurrence or metastasis has been reported to date. LESSONS: Curettage specimens may show only well-differentiated squamous epithelium, which is indistinguishable from normal squamous epithelium. It is difficult to infer from the histological morphology that the curettage specimens originate from the uterine cavity, which makes it difficult to diagnose PSCCE before the operation. We suggest that when an imaging examination indicates a tumor in the uterine cavity, even if multiple curettage specimens indicate normal or well-differentiated squamous epithelium, it indicates the possibility of PSCCE.
Subject(s)
Carcinoma, Squamous Cell , Endometrial Neoplasms , Female , Humans , Middle Aged , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/therapy , Endometrial Neoplasms/pathology , Endometrium/pathology , Uterus/pathology , Hysterectomy/methods , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgeryABSTRACT
The ubiquitin-proteasome system (UPS) plays an important role in virus-host interactions. However, the mechanism by which the UPS is involved in innate immunity remains unclear. In this study, we identified a novel major latex protein-like protein 43 (NbMLP43) that conferred resistance to Nicotiana benthamiana against potato virus Y (PVY) infection. PVY infection strongly induced NbMLP43 transcription but decreased NbMLP43 at the protein level. We verified that B-box zinc finger protein 24 (NbBBX24) interacted directly with NbMLP43 and that NbBBX24, a light responsive factor, acted as an essential intermediate component targeting NbMLP43 for its ubiquitination and degradation via the UPS. PVY, tobacco mosaic virus, (TMV) and cucumber mosaic virus (CMV) infections could promote NbMLP43 ubiquitination and proteasomal degradation to enhance viral infection. Ubiquitination occurred at lysine 38 (K38) within NbMLP43, and non-ubiquitinated NbMLP43(K38R) conferred stronger resistance to RNA viruses. Overall, our results indicate that the novel NbMLP43 protein is a target of the UPS in the competition between defense and viral anti-defense and enriches existing theoretical studies on the use of UPS by viruses to promote infection.
Subject(s)
Nicotiana , Plant Diseases , Potyvirus , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Ubiquitination , Nicotiana/virology , Plant Diseases/virology , Plant Proteins/metabolism , Potyvirus/pathogenicityABSTRACT
Potato virus Y (PVY) disease is a global problem that causes significant damage to crop quality and yield. As traditional chemical control methods are ineffective against PVY, it is crucial to explore new control strategies. MicroRNAs (miRNAs) play a crucial role in plant and animal defense responses to biotic and abiotic stresses. These endogenous miRNAs act as a link between antiviral gene pathways and host immunity. Several miRNAs target plant immune genes and are involved in the virus infection process. In this study, we conducted small RNA sequencing and transcriptome sequencing on healthy and PVY-infected N. benthamiana tissues (roots, stems, and leaves). Through bioinformatics analysis, we predicted potential targets of differentially expressed miRNAs using the N. benthamiana reference genome and the PVY genome. We then compared the identified differentially expressed mRNAs with the predicted target genes to uncover the complex relationships between miRNAs and their targets. This study successfully constructed a miRNA-mRNA network through the joint analysis of Small RNA sequencing and transcriptome sequencing, which unveiled potential miRNA targets and identified potential binding sites of miRNAs on the PVY genome. This miRNA-mRNA regulatory network suggests the involvement of miRNAs in the virus infection process.
ABSTRACT
Western flower thrips (Frankliniella occidentalis) are among the most important pests globally that transmit destructive plant viruses and infest multiple commercial crops. Lysine lactylation (Klac) is a recently discovered novel post-translational modification (PTM). We used liquid chromatography-mass spectrometry to identify the global lactylated proteome of F. occidentalis, and further enriched the identified lactylated proteins using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). In the present study, we identified 1,458 Klac sites in 469 proteins from F. occidentalis. Bioinformatics analysis showed that Klac was widely distributed in F. occidentalis proteins, and these Klac modified proteins participated in multiple biological processes. GO and KEGG enrichment analysis revealed that Klac proteins were significantly enriched in multiple cellular compartments and metabolic pathways, such as the ribosome and carbon metabolism pathways. Two Klac proteins were found to be involved in the regulation of the TSWV (Tomato spotted wilt virus) transmission in F. occidentalis. This study provides a systematic report and a rich dataset of lactylation in F. occidentalis proteome for potential studies on the Klac protein of this notorious pest.
ABSTRACT
Lysine acetylation (Kac), a reversible PTM, plays an essential role in various biological processes, including those involving metabolic pathways, pathogen resistance, and transcription, in both prokaryotes and eukaryotes. TMV, the major factor that causes the poor quality of Solanaceae crops worldwide, directly alters many metabolic processes in tobacco. However, the extent and function of Kac during TMV infection have not been determined. The validation test to detect Kac level and viral expression after TMV infection and Nicotinamide (NAM) treatment clarified that acetylation was involved in TMV infection. Furthermore, we comprehensively analyzed the changes in the proteome and acetylome of TMV-infected tobacco (Nicotiana benthamiana) seedlings via LC-MS/MS in conjunction with highly sensitive immune-affinity purification. In total, 2082 lysine-acetylated sites on 1319 proteins differentially expressed in response to TMV infection were identified. Extensive bioinformatic studies disclosed changes in acetylation of proteins engaged in cellular metabolism and biological processes. The vital influence of Kac in fatty acid degradation and alpha-linolenic acid metabolism was also revealed in TMV-infected seedlings. This study first revealed Kac information in N. benthamiana under TMV infection and expanded upon the existing landscape of acetylation in pathogen infection.