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Cephalotaxines harbor great medical potential, but their natural source, the endemic conifer Cephalotaxus is highly endangered, creating a conflict between biotechnological valorization and preservation of biodiversity. Here, we construct the whole biosynthetic pathway to the 1-phenethylisoquinoline scaffold, as first committed compound for phenylethylisoquinoline alkaloids (PIAs), combining metabolic modeling, and transcriptome mining of Cephalotaxus hainanensis to infer the biosynthesis for PIA precursor. We identify a novel protein, ChPSS, driving the Pictet-Spengler condensation and show that this enzyme represents the branching point where PIA biosynthesis diverges from the concurrent benzylisoquinoline-alkaloids pathway. We also pinpoint ChDBR as crucial step to form 4-hydroxydihydrocinnamaldehyde diverging from lignin biosynthesis. The elucidation of the early PIA pathway represents an important step toward microbe-based production of these pharmaceutically important alkaloids resolving the conflict between biotechnology and preservation of biodiversity.
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Alcaloides , Bencilisoquinolinas , Cephalotaxus , Cephalotaxus/genética , BiotecnologíaRESUMEN
Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.
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Hedera , Ácido Oleanólico/análogos & derivados , Saponinas , Glicosiltransferasas/genéticaRESUMEN
AIM: High-intensity focused ultrasound (HIFU) is a non-invasive treatment of adenomyosis. Uterine rupture during pregnancy is a rare adverse event after HIFU treatment, because HIFU treatment results in tissue coagulative necrosis. METHODS: We reported a case of uterine rupture in a 34-year-old woman. The woman had HIFU treatment for adenomyosis eight months before unplanned pregnancy. She was closely monitored during the pregnancy and the antenatal course was uneventful. At the gestational age of 38 weeks and 2 days, an emergency lower segment cesarean section was performed because of inexplainable abdominal pain. After delivery of the fetus, a 2 × 2 cm serous membrane rupture was observed in the HIFU treatment area. CONCLUSION: Uterine rupture during pregnancy after HIFU is a rare adverse event, however, attention is required during the whole pregnancy in case of unexpected uterine rupture.
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Adenomiosis , Ultrasonido Enfocado de Alta Intensidad de Ablación , Rotura Uterina , Adulto , Femenino , Humanos , Embarazo , Adenomiosis/diagnóstico por imagen , Adenomiosis/cirugía , Cesárea , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Resultado del Tratamiento , Rotura Uterina/etiología , Rotura Uterina/terapiaRESUMEN
This study aimed to explore the clinical efficacy of ultrasound-guided interventional therapy in patients with benign ovarian cysts through meta-analysis. A literature search was performed on PubMed, Web of Science, Embase, CNKI, and WanFang databases to obtain clinical randomized controlled trials on ultrasound-guided interventional therapy for benign ovarian cysts published between 2010 and 2022. A total of 1395 studies were initially retrieved, and finally 12 studies were included for meta-analysis. The results showed that the observation group (ultrasound-guided interventional therapy) had higher treatment effective rate than the control group (conventional laparotomy or laparoscopic cyst resection), but the incidence of adverse reactions was markedly lower. Additionally, the length of hospital stay, intraoperative blood loss, and operation time showed significant lower levels in the observation group. In terms of ovarian function, postoperative luteinizing hormone and follicle-stimulating hormone levels in the observation group were lower than the control group, while oestradiol levels were higher. In conclusion, compared with conventional surgical treatment, ultrasound-guided interventional therapy can significantly improve the clinical effective rate, shorten the hospital stay and reduce intraoperative blood loss. Such therapy can protect ovarian reserve, with high value of clinical promotion.IMPACT STATEMENTWhat is already known on this subject? Main surgical methods for ovarian cysts consist of laparotomy, laparoscopic surgery, and interventional therapy.What the results of this study add? With the advancement of surgical techniques and instruments, many minimally invasive surgeries have been applied to treat ovarian cysts with good clinical results. However, there is no exact evidence to prove its clinical efficacy. Given the lack in this field, we conducted a meta-analysis of all clinical studies of ultrasound-guided interventional therapy for ovarian cysts to evaluate its efficacy and safety.What the implications are of these findings for clinical practice and/or further research? Compared with conventional laparotomic or laparoscopic cyst resection, ultrasound-guided interventional therapy for ovarian cysts significantly improves the treatment effectiveness, shortens the hospital stay and reduces intraoperative blood loss. This therapy with good clinical efficacy also has advantages of small wound, rapid recovery and less adverse reactions, and can protect ovarian reserve. This safe and effective surgical method for ovarian cysts is worth promoting clinically.
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Laparoscopía , Quistes Ováricos , Femenino , Humanos , Pérdida de Sangre Quirúrgica , Quistes Ováricos/cirugía , Resultado del Tratamiento , Laparoscopía/métodos , Ultrasonografía Intervencional/métodosRESUMEN
A glycosyl transferase, isolated from Angelica decursiva a medical herb rich in coumarin, shows C-glycosyl transferase activity by in vitro activity assay using 5,7-dihydroxycoumarin as substrate, producing a C-glycosylated product at position C'8 along with the main product at C'6 position. Catalytic promiscuity assay shows that AdCGT also displays O- or C-glycosylation activity to other coumarins and flavonoids. When phloretin and 2,4,6-trihydroxyacetophenone were fed as substrates, AdCGT catalyzed the formation of di-C-glycosides. Therefore, AdCGT is a multifunctional glycosyltransferase with a broad substrate acceptability. This work highlights the potential of AdCGT as a catalyst for glycosylation of coumarin and reveals a new regio-selective C-glycosyltransferase, providing a basis for exploring the mechanism of coumarin glycosylation.
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Angelica , Angelica/química , Angelica/metabolismo , Biocatálisis , Cumarinas/química , Glicósidos , Glicosiltransferasas/metabolismoRESUMEN
OBJECTIVE: Cervical cancer diagnosed during pregnancy is a rare event, and data regarding efficacy of cancer treatment during pregnancy is limited. This study aimed to assess the safety of continuation of the pregnancy for mother and fetus when concomitantly diagnosed with cervical cancer. METHODS: This study retrospectively analyzed all cervical cancer patients diagnosed while pregnant or immediately postpartum, inclusive from Jan 2010 to June 2019 at our institute. Patient clinical details and follow-up were obtained from hospital records. RESULTS: The study comprised 40 patients with clinical cancer stages of IA1 (1/40, 2.5%); IB1 (15/40, 37.5%); IB2 (10/40, 25%); IIA (12/40, 30%); and IIB (2/40, 5%). There were 38 patients diagnosed during pregnancy, and 2 diagnosed in the postpartum period. Of the 38 patients, 17 were diagnosed in the first trimester, 13 in the second trimester, and 8 in the third trimester. 10 of 38 patients (26.3%) continued their pregnancy after learning of their diagnosis; 7 (70%) in the third trimester and 3 (30%) in the second trimester. The mean time from diagnosis to surgery in the patients who continued their pregnancy was 52.7 days, which was statistically significantly greater than the termination of pregnancy group (52.7 vs. 16.3 days, P < 0.01). Notably, there was no survival difference between the 2 groups (100% vs. 90.91%, P = 0.54), and none of the pregnant women who ultimately died had delayed treatment due to pregnancy. Similarly, the surgical estimated blood loss and operative duration comparison in the 2 groups were not significantly different. CONCLUSIONS: In the present study, the gestational age of pregnancy at the time of initial diagnosis of cervical cancer was an important determinant in the disease management. Continuation of the pregnancy when diagnosed with cervical cancer may not affect the oncologic outcome of the mother nor increase either surgical or obstetric complications. Additionally, the use of neoadjuvant chemotherapy did not threaten the health of the fetus. These results may be useful in counseling patients facing the diagnosis of cervical cancer during pregnancy.
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Carcinoma de Células Escamosas , Complicaciones Neoplásicas del Embarazo , Neoplasias del Cuello Uterino , Femenino , Humanos , Terapia Neoadyuvante , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapiaRESUMEN
BACKGROUND: Venous Thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with ovarian malignancy. There is no meta-analysis available on this topic so far. The aim of our study was to quantitatively synthesize the data from studies with respect to the incidence and risk factors for postoperative VTE among cases with epithelial ovarian cancer (EOC). METHODS: PubMed, Web of Science, and Embase were searched for papers containing the key words "venous thromboembolism", "postoperative", "postoperation", "ovarian neoplasm", "ovary neoplasm", "ovarian cancer", "ovary cancer", and "cancer of ovary". Studies selection, data extraction, quality assessment of eligible studies were performed independently by our different reviewers. Meta-analyses were conducted to determine postoperative VTE incidence and risk factors in women with EOC. Sensitivity analysis were used to verify the robustness of the results of meta-analyses if necessary. RESULTS: In total, 19 studies were included in this meta-analysis. The pooled incidence for postoperative symptomatic VTE was 3% (95% CI, 0.03-0.04) and for postoperative symptomatic as well as asymptomatic VTE was 8% (95% CI, 0.07-0.09). The presence of history of VTE (OR, 2.37), advanced-stages (OR, 2.35), high complexity of surgery (OR, 2.20), clear cell carcinoma of ovary (OR, 2.53) and residual disease>1 cm (OR, 2.57) significantly increase the likelihood of having postoperative VTE. Other risk factors for postoperative VTE in EOC patients were BMI>30 (OR, 1.58), per 10-years increase in age (OR, 1.22), ASA score>2 (OR, 1.45), ascites (OR, 2.07), the diameter of residual disease is between 0 cm to 1 cm (OR, 2.06) and smoking history (OR, 1.54). CONCLUSIONS: This study revealed that VTE, especially subclinical VTE, is a prevalent complication in postoperative patients with EOC. History of VTE, advanced FIGO stages, high complexity of surgery, obesity, older age, ascites, higher ASA score, smoking history and suboptimal debulking are associated with this increased incidence of postoperative VTE among patients with EOC. PROSPERO registration number: CRD42020209662.
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Carcinoma Epitelial de Ovario/cirugía , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Neoplasias Ováricas/cirugía , Complicaciones Posoperatorias/epidemiología , Tromboembolia Venosa/epidemiología , Ascitis/epidemiología , Ascitis/etiología , Índice de Masa Corporal , Carcinoma Epitelial de Ovario/complicaciones , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/patología , Femenino , Humanos , Incidencia , Estadificación de Neoplasias , Neoplasia Residual , Estudios Observacionales como Asunto , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Ovario/patología , Ovario/cirugía , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Fumar/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
CONTEXT: Lung cancer still remains the leading cause of cancer-related mortality worldwide. Bone is one of preferred metastatic sites for lung cancer cells. So far, both accurate diagnosis and effective treatment of lung cancer bone metastases are difficult. OBJECTIVE: This review aimed to evaluate roles of bone turnover markers (BTMs), microRNAs (miRNAs), dickkopf1 (DKK1) and insulin like growth factor binding protein 3 (IGFBP-3) in lung cancer bone metastases. METHODS: We searched articles about these four biomarkers in lung cancer bone metastases mainly in PubMed. RESULT: The levels of bone specific alkaline phosphatase (BALP), cross-linked carboxy-terminal telopeptide of type-I collagen (ICTP) and N-terminal telopeptides of type-I collagen (NTX) were reported to be significantly increased in lung cancer patients with bone metastases. ALP, NTX and bone sialoprotein were thought to be associated with prognosis of lung cancer patients with bone metastases. MiRNA-335, miRNA-33a, miRNA-21, DKK1 and IGFBP-3 were revealed to be novel biomarkers in lung cancer bone metastases. DISCUSSION AND CONCLUSION: Current researches have revealed that BTMs, miRNAs, DKK1 and IGFBP-3 may be useful in diagnosis, prognosis evaluation or treatment of lung cancer bone metastases. More studies about these biomarkers in lung cancer bone metastases are needed.
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Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/metabolismo , Huesos/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfatasa Alcalina/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Colágeno Tipo I/metabolismo , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/genéticaRESUMEN
OBJECTIVES: To study the effect of high mobility group chromosomal protein N2 on inhibiting cervical cancer in nude mice. METHODS: Model of cervical cancer were established in nude mice. They were randomly divided into 4 groups including negative control group, HMGN2 group, cisplatin group and HMGN2 with cisplatin group. After 4 injections, the tumor size were calculated and tumor tissues were stained by haematoxylin eosin (HE) staining. RESULTS: Transplated tumor models were established successfully. The tumor sizes of negative control group [(0.38±0.12) cm³] were significantly lower than those of HMGN2 group [(0.14±0.07)cm³, cisplatin group [(0.11±0.06) cm³] and HMGN2 combined with cisplatin group[(0.11±0.07) cm³]. No differences were detected in HMGN2 group, cisplatin group and HMGN2 with cisplatin group in tumor sizes. The tumor inhibition rates of HMGN2 group, cisplatin group and HMGN2 with cisplatin group were 0.62±0.18, 0.71±0.17 and 0.70±0.18, respectively. The necrosis area were smaller in negative control group than in other three groups by HE staining. CONCLUSIONS: HMGN2 has a significant inhibitory effect on transplanted cervical cancer in nude mice.
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Cisplatino/farmacología , Proteína HMGN2/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To explore the expression of IL-10 and IL-17 in endometrial cancer and their relationships with tumor progression. METHODS: The sera levels of IL-10 and IL-17 were detected by enzyme-linked immune-sorbent assay in 15 benign hysterectomies and 15 endometrial cancers, the expressions of IL-10 and IL-17 in the tissue were measured by immunohistochemistry assay (SABC) with the evaluation of IOD value, clinic-pathological characteristics were retrieved and analyzed. RESULTS: Both sera expression and tissue IOD value of IL-10 were significantly higher in endometrial cancer than those in benign uterine, while no difference was found in IL-17 between the two groups. Sera IL-10 of I B-II stage, G2-G3, with myoinvasion, with vas tumor emboli was higher than that of I A stage, G1, without myoinvasion, and without vas tumor emboli, while no difference was found among tissue types. Sera IL-17 of I B-II stage, with myoinvasion, with vas tumor emboli was lower than that of IA stage, without myoinvasion, and without vas tumor emboli, while no difference was found among tumor grades nor tissue types. CONCLUSION: High expression of IL-10 may participate in the genesis and development of uterine endometrial cancer, while low expression of IL-17 may participate in its development.
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Neoplasias Endometriales/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Interleucina-10/sangre , Interleucina-17/sangreRESUMEN
Infertility affects approximately 15% of couples at child-bearing ages and assisted reproductive technologies (ART), especially in vitro fertilization and embryo transfer (IVF-ET), provided infertile patients with an effective solution. The current paradox is that multiple embryo transfer that may leads to severe obstetric and perinatal complications seems to be the most valid measure to secure high success rate in the majority of clinic centers. Therefore, to avoid multiple transfer of embryos, it is urgent to explore biomarkers for IVF prognosis to select high-quality oocytes and embryos. Follicular fluid (FF), a typical biofluid constituted of the plasma effusion and granulosa-cell secretion, provides essential intracellular substances for oocytes maturation and its variation in composition reflects oocyte developmental competence and embryo viability. With the advances in metabolomics methodology, metabolomics, as an accurate and sensitive analyzing method, has been utilized to explore predictors in FF for ART success. Although FF metabolomics has provided a great possibility for screening markers with diagnostic and predictive value, its effectiveness is still doubted by some researchers. This may be resulted from the ignorance of the impact of sterility causes on the FF metabolomic profiles and thus its predictive ability might not be rightly illustrated. Therefore, in this review, we categorically demonstrate the study of FF metabolomics according to specific infertility causes, expecting to reveal the predicting value of metabolomics for IVF outcomes.
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In traditional Chinese medicine, Angelica dahurica is a valuable herb with numerous therapeutic applications for a range of ailments. There have not yet been any articles on the methodical assessment and choice of the best reference genes for A. dahurica gene expression studies. Real-time quantitative PCR (RT-qPCR) is widely employed as the predominant method for investigating gene expression. In order to ensure the precise determination of target gene expression outcomes in RT-qPCR analysis, it is imperative to employ stable reference genes. In this study, a total of 11 candidate reference genes including SAND family protein (SAND), polypyrimidine tract-binding protein (PTBP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), TIP41-like protein (TIP41), cyclophilin 2 (CYP2), elongation factor 1 α (EF1α), ubiquitin-protein ligase 9 (UBC9), tubulin ß-6 (TUB6), thioredoxin-like protein YLS8 (YLS8), and tubulin-α (TUBA) were selected from the transcriptome of A. dahurica. Subsequently, three statistical algorithms (geNorm, NormFinder, and BestKeeper) were employed to assess the stability of their expression patterns across seven distinct stimulus treatments. The outcomes obtained from these analyses were subsequently amalgamated into a comprehensive ranking using RefFinder. Additionally, one target gene, phenylalanine ammonia-lyase (PAL), was used to confirm the effectiveness of the selected reference genes. According to the findings of this study, the two most stable reference genes for normalizing the expression of genes in A. dahurica are TIP41 and UBC9. Overall, our research has determined the appropriate reference genes for RT-qPCR in A. dahurica and provides a crucial foundation for gene screening and identifying genes associated with the biosynthesis of active ingredients in A. dahurica.
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Angelica , Angelica/genética , Tubulina (Proteína) , Actinas , Reacción en Cadena en Tiempo Real de la Polimerasa , Estrés FisiológicoRESUMEN
This research examined the impact of exogenous thermophilic bacteria and ripening agents on greenhouse gas (GHG) emission, enzyme activity, and microbial community during composting. The use of ripening agents alone resulted in a 30.9 % reduction in CO2 emissions, while the use of ripening agents and thermophilic bacteria resulted in a 50.8 % reduction in N2O emissions. Pearson's analysis showed that organic matter and nitrate nitrogen were the key parameters affecting GHG emissions. There was an inverse correlation between CO2 and CH4 releases and methane monooxygenase α subunit and N2O reductase activity (P<0.05). Additionally, N2O emissions were positively related to ß-1, 4-N-acetylglucosaminidase, and ammonia monooxygenase activity (P<0.05). Deinococcota, Chloroflexi, and Bacteroidota are closely related to CO2 and N2O emissions. Overall, adding thermophilic bacteria represents an effective strategy to mitigate GHG emissions during composting.
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Bacterias , Compostaje , Gases de Efecto Invernadero , Bacterias/metabolismo , Compostaje/métodos , Dióxido de Carbono , Metano/metabolismo , Óxido Nitroso/metabolismo , Microbiología del Suelo , Microbiota/fisiología , Suelo/químicaRESUMEN
Complex coumarins (CCs) represent characteristic metabolites found in Apiaceae plants, possessing significant medical value. Their essential functional role is likely as protectants against pathogens and regulators responding to environmental stimuli. Utilizing genomes and transcriptomes from 34 Apiaceae plants, including our recently sequenced Peucedanum praeruptorum, we conduct comprehensive phylogenetic analyses to reconstruct the detailed evolutionary process of the CC biosynthetic pathway in Apiaceae. Our results show that three key enzymes - p-coumaroyl CoA 2'-hydroxylase (C2'H), C-prenyltransferase (C-PT), and cyclase - originated successively at different evolutionary nodes within Apiaceae through various means of gene duplications: ectopic and tandem duplications. Neofunctionalization endows these enzymes with novel functions necessary for CC biosynthesis, thus completing the pathway. Candidate genes are cloned for heterologous expression and subjected to in vitro enzymatic assays to test our hypothesis regarding the origins of the key enzymes, and the results precisely validate our evolutionary inferences. Among the three enzymes, C-PTs are likely the primary determinant of the structural diversity of CCs (linear/angular), due to divergent activities evolved to target different positions (C-6 or C-8) of umbelliferone. A key amino acid variation (Ala161/Thr161) is identified and proven to play a crucial role in the alteration of enzymatic activity, possibly resulting in distinct binding forms between enzymes and substrates, thereby leading to different products. In conclusion, this study provides a detailed trajectory for the establishment and evolution of the CC biosynthetic pathway in Apiaceae. It explains why only a portion, not all, of Apiaceae plants can produce CCs and reveals the mechanisms of CC structural diversity among different Apiaceae plants.
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Apiaceae , Vías Biosintéticas , Cumarinas , Filogenia , Cumarinas/metabolismo , Vías Biosintéticas/genética , Apiaceae/genética , Apiaceae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Evolución Molecular , Duplicación de GenRESUMEN
Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.
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Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high-risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high-risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV-related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV-related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV-related cervical lesions.
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Tumor metabolism and tumor immunity are inextricably linked. Targeting the metabolism of tumors is a point worth studying in tumor immunotherapy. Recently, the influence of the metabolism of tumors and immune cells on the occurrence, proliferation, metastasis, and prognosis of tumors has attracted more attention. Tumor tissue forms a specific tumor microenvironment (TME). In addition to tumor cells, there are also immune cells, stromal cells, and other cells in TME. To adapt to the environment, tumor cells go through the metabolism reprogramming of various substances. The metabolism reprogramming of tumor cells may further affect the formation of the tumor microenvironment and the function of a variety of cells, especially immune cells, eventually promoting tumor development. Therefore, it is necessary to study the metabolism of tumor cells and its effects on immune cells to guide tumor immunotherapy. Inhibiting tumor metabolism may restore immune balance and promote the immune response in tumors. This article will describe glucose metabolism, lipid metabolism, amino acid metabolism, and immune cells in tumors. Besides, the impact of metabolism on the immune cells in TME is also discussed for analyzing and exploring tumor immunotherapy.
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Metabolismo de los Lípidos , Microambiente Tumoral , Inmunoterapia , Células del EstromaRESUMEN
OBJECTIVE: To study the anti-cancer activities of Z-Leu-Leu-Leu-cho (MG132) against human endometrial carcinoma HEC-1B and Ishikawa cells and the potential of MG132 in human endometrial cancer therapy. METHODS: HEC-1B and Ishikawa cells were treated with MG132. Cell proliferation was assessed by MTT while cell apoptosis rate and cell-cycle distribution were assessed by flow cytometry. RESULTS: The proliferation of HEC-1B and Ishikawa cells was inhibited by MG132 and cell proliferation was significantly inhibited with the raised concentration of MG132 (P<0.01), Ishikawa cells were more sensitive than HEC-1B cells to MG132. MG132 could induce the apoptosis of HEC-1B and Ishikawa cells (P = 0.000). Cell cycle analysis indicated that the percentage of HEC-1B cells was increased in G2 phase (P<0.05) while Ishikawa cells' was increased in G1 and G2 phase (P<0.05). CONCLUSION: Proteasome inhibitor MG132 could inhibit the proliferation, promote cell apoptosis, and block the cell cycle of HEC-1B and Ishikawa cells. MG132 may be a potential treatment for endometrial cancer.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Endometriales/patología , Leupeptinas/farmacología , Inhibidores de Proteasoma/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , HumanosRESUMEN
OBJECTIVE: To compare the long-term survival outcomes of patients with apparent early-stage uterine serous carcinoma (USC) who underwent laparoscopic staging surgery with those who underwent open surgical staging. METHODS: A total of 295 patients from four Chinese teaching hospitals were included. Overall survival (OS) and disease-free survival (DFS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients after laparoscopic surgery or open surgery. The Cox proportional hazards regression model was applied to adjust for potential confounding factors. RESULTS: For patients with apparent early-stage USC, laparoscopic surgery was associated with deteriorated DFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.15-2.93, P = 0.012), and there was no significant difference in OS between the two groups (HR 1.74, 95% CI 0.99-3.08, P = 0.056). However, after adjusting for confounding factors, the surgical approach was not an independent prognostic factor for DFS (adjusted HR 1.16, 95% CI 0.63-2.12, P = 0.636) and OS (adjusted HR 1.11, 95% CI 0.52-2.38, P = 0.794) in apparent early-stage USC. CONCLUSION: For apparent early-stage USC, laparoscopic surgery is safe. This needs to be confirmed by future prospective clinical trials.
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Cistadenocarcinoma Seroso , Laparoscopía , Neoplasias Uterinas , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Laparoscopía/efectos adversos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Uterinas/patologíaRESUMEN
Psoralea corylifolia L. is a popular herb and has long been used in traditional Ayurvedic and Chinese medicine owing to its extensive pharmacological activities, especially in the treatment of various shin diseases. To date, the systematic evaluation and selection of the optimum reference genes for gene expression analysis of P. corylifolia were not reported. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a method for gene expression quantification. Selecting appropriate reference genes is the prerequisite for accurate normalization of RT-qPCR results. This study assessed the expression stability of 10 candidate reference genes under different abiotic stresses. First, amplification primers for RT-qPCR were designed and received testing and optimization. Then, expression data from each candidate gene were evaluated based on three statistical algorithms, and their results were further integrated into a comprehensive ranking based on the geometric mean. Additionally, one target gene, i.e., 1-aminocyclopropane-1-carboxylate oxidase (ACO), was used to validate the effectiveness of the selected reference. Our analysis suggested that thioredoxin-like protein YLS8 (YLS8), TIP41-like family protein (TIP41), and cyclophilin 2 (CYP2) genes provided superior expression normalization under different abiotic stresses. Overall, this work constitutes the first effort to select optimal endogenous controls for RT-qPCR studies of gene expression in P. corylifolia. It also provides a reasonable normalization standard and basis for further analysis of the gene expression of bioactive components in P. corylifolia.