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1.
J Am Chem Soc ; 146(6): 4112-4122, 2024 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-38226918

RESUMEN

Lipoarabinomannan (LAM) from the Mycobacterium tuberculosis cell envelope represents important targets for the development of new therapeutic agents against tuberculosis, which is a deadly disease that has plagued mankind for a long time. However, the accessibility of long, branched, and complex lipoarabinomannan over 100-mer remains a long-standing challenge. Herein, we report the modular synthesis of mannose-capped lipoarabinomannan 101-mer from the M. tuberculosis cell wall using a one-pot assembly strategy on the basis of glycosyl ortho-(1-phenylvinyl)benzoates (PVB), which not only accelerates the modular synthesis but also precludes the potential problems associated with one-pot glycosylation with thioglycosides. Shorter sequences including 18-mer, 19-mer, and 27-mer are also synthesized for in-depth structure-activity relationship biological studies. Current synthetic routes also highlight the following features: (1) streamlined synthesis of various linear and branched glycans using one-pot orthogonal glycosylation on the combination of glycosyl N-phenyltrifluoroacetimidates, glycosyl ortho-alkynylbenzoates, and glycosyl PVB; (2) highly stereoselective construction of 10 1,2-cis-arabinofuranosyl linkages using 5-O-(2-quinolinecarbonyl)-directing 1,2-cis-arabinofuranosylation via a hydrogen-bond-mediated aglycone delivery strategy; and (3) convergent [(18 + 19) × 2 + 27] one-pot synthesis of the 101-mer LAM polysaccharide. The present work demonstrates that this orthogonal one-pot glycosylation strategy can highly streamline the chemical synthesis of long, branched, and complex polysaccharides.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Manosa , Lipopolisacáridos , Polisacáridos , Pared Celular
2.
BMC Cancer ; 24(1): 381, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38528547

RESUMEN

BACKGROUND: Inaccurate colposcopy diagnosis may lead to inappropriate management and increase the incidence of cervical cancer. This study aimed to evaluate the diagnostic accuracy of colposcopy in the detection of histologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with transformation zone type 3 (TZ3). METHODS: Records from 764 patients with TZ3 who underwent colposcopy-directed biopsy and/or endocervical curettage in Putuo Hospital China between February 2020 and March 2023 were retrospectively collected. Colposcopy was carried out based on 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) and Colposcopy nomenclature. The diagnostic performance of colposcopy for identifying CIN2 + was evaluated compared with biopsies. The Kappa and McNemar tests were used to perform statistical analyses. RESULTS: Among the study population, 11.0% had pathologic CIN2+. The relative sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of colposcopy for histologic CIN2 + were 51.2%, 96.5%, 64.2% and 94.1%, respectively. The senior colposcopists (80.6%) had a higher colposcopic accuracy to diagnose histologic CIN2 + than junior colposcopists (68.6%). In subgroup analyses, age group ≥ 60 years (70.3%) showed lowest diagnostic accuracy when compared with age groups of < 45 years (84.4%) and 45-59 years (74.9%). CONCLUSION: Our findings suggest an increased risk of diagnostic inaccuracy of colposcopy in identifying CIN2 + in those ≥ 60 years of age with TZ3, and the accuracy of colposcopy is required to be further improved.


Asunto(s)
Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Embarazo , Persona de Mediana Edad , Colposcopía , Estudios Retrospectivos , Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Biopsia
3.
J Biochem Mol Toxicol ; 38(1): e23581, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38044485

RESUMEN

Colorectal cancer (CRC) is a common digestive tract tumor with a high incidence and a poor prognosis. Traditional chemotherapy drugs are usually accompanied by unpleasant side effects, highlighting the importance of exploring new adjunctive drugs. In this study, we aimed to explore the role of ursolic acid (UA) in CRC cells. Specifically, HT-29 cells were treated with UA at different concentrations (10, 20, 30, and 40 µM), and the expression of miR-140-5p, tumor growth factor-ß3 (TGF-ß3), ß-catenin, and cyclin D1 was determined by real-time quantitative PCR. The cell cycle and apoptosis were checked by flow cytometry, and cell proliferation was detected by Cell Counting Kit-8 assay. The HT-29 cell model was established through overexpression (miR-140-5p mimics) and interference (miR-140-5p inhibitor) of miR-140-5p. Western blot was used to detect the protein expression of TGF-ß3. We found that UA could inhibit the proliferation of HT-29 cells, block cells in the G1 phase, and promote cell apoptosis. After UA treatment, the expression of miR-140-5p increased and TGF-ß3 decreased. Notably, miR-140-5p downregulated the expression of TGF-ß3, while the overexpression of miR-140-5p exerted a similar function to UA in HT-29 cells. Additionally, the messenger RNA expression of TGF-ß3, ß-catenin, and cyclin D1 was decreased in HT-29 cells after UA treatment. In conclusion, UA inhibited CRC cell proliferation and cell cycle and promoted apoptosis by regulating the miR-140-5p/TGF-ß3 axis, which may be related to the inhibition of Wnt/ß-catenin signaling pathway.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , beta Catenina/metabolismo , MicroARNs/metabolismo , Línea Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Factor de Crecimiento Transformador beta3/genética , Factor de Crecimiento Transformador beta3/metabolismo , Ácido Ursólico , Regulación hacia Abajo , Proliferación Celular/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica
4.
Artículo en Inglés | MEDLINE | ID: mdl-38569482

RESUMEN

Setting 7 subsection in abstract Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high-glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study was aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. DESIGN: This is an in vitro experimental study. PARTICIPANTS: A total of 10 pregnant women with severe preeclampsia (PE) and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. METHODS: The expression and localization of necrotic proteins were assayed in human placenta samples and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). RESULTS: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine-ß-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. LIMITATIONS: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of preeclampsia. CONCLUSIONS: we proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1, and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against CER-induced necroptosis via the p38MAPK pathway.

5.
J Stroke Cerebrovasc Dis ; 33(1): 107461, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38000110

RESUMEN

BACKGROUND: Although most stroke patients have underlying vascular risk factors, it is important to consider infectious causes of stroke in young adults without traditional risk factors or patients with cryptogenic stroke. Pulmonary vein thrombosis and air embolism can potentially cause cerebral infarction. However, the association between infection and pulmonary vein thrombosis or air embolism is often overlooked. In this case, we present a rare infectious cause of stroke and air embolism involving a pulmonary abscess and pulmonary vein thrombosis. CASE PRESENTATION: A 37-year-old male patient initially presented with right-sided pneumonia. During treatment at a local hospital, he developed headaches and left limb weakness. Subsequently, he was transferred to our hospital due to septic shock. Neurological evaluations revealed multiple brain foci and thrombosis in the right superior pulmonary vein. Following treatment with broad-spectrum antibiotics and anticoagulants, the patient's clinical symptoms and inflammatory markers showed improvement. However, a computed tomography scan revealed the formation of a pulmonary abscess, and the patient experienced coma and epilepsy after severe coughing with massive hemoptysis. Multiple air embolisms were observed in the brain computed tomography. Eventually, the patient's family chose to discharge him from the hospital. CONCLUSIONS: This case highlights the rare and complex etiologies of stroke associated with infection in a young patient. Early detection, diagnosis, and appropriate treatment of infected systemic embolism in young patients are crucial to prevent serious complications.


Asunto(s)
Embolia Aérea , Absceso Pulmonar , Embolia Pulmonar , Venas Pulmonares , Accidente Cerebrovascular , Trombosis de la Vena , Humanos , Masculino , Adulto Joven , Adulto , Absceso Pulmonar/complicaciones , Absceso Pulmonar/diagnóstico por imagen , Absceso Pulmonar/terapia , Venas Pulmonares/diagnóstico por imagen , Trombosis de la Vena/complicaciones , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/tratamiento farmacológico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/diagnóstico por imagen , Embolia Pulmonar/diagnóstico
6.
BMC Womens Health ; 23(1): 411, 2023 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-37542333

RESUMEN

BACKGROUND: HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. METHODS: This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. RESULTS: Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54-26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56-13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12-3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P<0.001). Among women with low-grade cytology, 24.1% had CIN2+, and the risks for HPV16/18 (58.2%) were higher than for other HR-HPV(16.8%). For those with high-grade cytology, there was no significant difference between HPV groups ( 75.0% vs. 72.9%, P > 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. CONCLUSIONS: The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.


Asunto(s)
Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Femenino , Humanos , Colposcopía , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Estudios Transversales , Papillomavirus Humano 18/genética , China , Displasia del Cuello del Útero/diagnóstico , Lesiones Intraepiteliales Escamosas/complicaciones , Papillomaviridae/genética , Detección Precoz del Cáncer/métodos
7.
Int J Mol Sci ; 24(21)2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37958903

RESUMEN

The tumor microenvironment plays a critical role in tumor progression and immune regulation. As one of the most important components of the tumor microenvironment, macrophages have become a new therapeutic target for inhibiting tumor progression. Despite the well-documented anticancer activity of cucurbitacin I, its effect on macrophages remains unclear. In this study, we established a coculture system of macrophages and cancer cells under hypoxic conditions to simulate the tumor-promoting environment mediated by M2-like macrophages. We determined whether cucurbitacin I modulates M2-like polarization in macrophages in vitro and conducted RNA sequencing to identify gene expression changes induced by cucurbitacin I in macrophages. The results indicated a remarkable inhibition of the M2-like polarization phenotype in macrophages following treatment with cucurbitacin I, which was accompanied by the significant downregulation of heme oxygenase-1. Moreover, we found that cucurbitacin I-treated macrophages reduced the migration of cancer cells by inhibiting the M2 polarization in vitro. These findings highlight the potential of cucurbitacin I as a therapeutic agent that targets M2-like macrophages to inhibit cancer cell metastasis. Our study provides novel insights into the intricate interplay among macrophage polarization, cucurbitacin I, and heme oxygenase-1, thereby opening new avenues for cancer treatment.


Asunto(s)
Neoplasias , Transducción de Señal , Macrófagos Asociados a Tumores , Hemo-Oxigenasa 1 , Línea Celular Tumoral
8.
Int J Mol Sci ; 24(21)2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37958642

RESUMEN

Various studies have shown that the cell-cycle-related regulatory proteins UBE2C, PLK1, and BIRC5 promote cell proliferation and migration in different types of cancer. However, there is a lack of in-depth and systematic research on the mechanism of these three as therapeutic targets. In this study, we found a positive correlation between the expression of UBE2C and PLK1/BIRC5 in the Cancer Genome Atlas (TCGA) database, revealing a potential combination therapy candidate for pan-cancer. Quantitative real-time PCR (qRT-PCR), Western blotting (WB), cell phenotype detection, and RNA-seq techniques were used to evidence the effectiveness of the combination candidate. We found that combined interference of UBE2C with PLK1 and UBE2C with BIRC5 affected metabolic pathways by significantly downregulating the mRNA expression of IDH1 and ACLY, which was related to the synthesis of acetyl-CoA. By combining the PLK1 inhibitor volasertib and the ACLY inhibitor bempedoic acid, it showed a higher synergistic inhibition of cell viability and higher synergy scores in seven cell lines, compared with those of other combination treatments. Our study reveals the potential mechanisms through which cell-cycle-related genes regulate metabolism and proposes a potential combined targeted therapy for patients with higher PLK1 and ACLY expression in pan-cancer.


Asunto(s)
Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proliferación Celular , División Celular , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo
9.
FASEB J ; 35(5): e21565, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33864414

RESUMEN

The uterus undergoes distinct molecular and functional changes during pregnancy and parturition. These processes are associated with the dramatic changes in various proteins. Given that the maturation and activation of many proteins require proteolytic processing by proprotein convertases (PCs), we sought to explore the role of PCs in uterine activation for labor. First, we found that furin was the most dramatically increased PC member in myometrial tissues from the pregnant women after onset of labor at term. Using the model of cultured human myometrial smooth muscle cells (HMSMCs), we showed that furin inhibitor CMK, D6R treatment and furin siRNA transfection suppressed contractility. Inhibition of furin activity or interfering furin expression decreased connexin 43 (CX43), prostaglandin (PG) endoperoxide synthase-2 (COX-2) and PGF2α receptor (FP) expression and NF-κB activation. In mouse model, administration of furin inhibitors prolonged gestational length. However, D6R treatment did not affect RU38486- and lipopolysaccharides (LPS)-induced preterm birth. Furthermore, D6R and furin siRNA treatment reduced the release of soluble form of tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK), while furin overexpression led to an increase in soluble TWEAK release in cultured HMSMCs. D6R treatment decreased TWEAK level in blood of pregnant mice. TWEAK treatment promoted contractility and NF-κB activation, while TWEAK receptor fibroblast growth factor-inducible 14 (FN14) antagonist treatment inhibited contractility and NF-κB activation in HMSMCs. In pregnant mice, administration of FN14 antagonist prolonged gestational length. Our data suggest that furin can act as a stimulator for uterine activation for labor at term. TWEAK is one of the potential substrates which mediate furin regulation of parturition initiation.


Asunto(s)
Modelos Animales de Enfermedad , Furina/metabolismo , Regulación de la Expresión Génica , Trabajo de Parto , Miocitos del Músculo Liso/fisiología , Miometrio/fisiología , Contracción Uterina , Animales , Células Cultivadas , Femenino , Furina/genética , Humanos , Ratones , Ratones Endogámicos ICR , Miocitos del Músculo Liso/citología , Miometrio/citología , FN-kappa B/genética , FN-kappa B/metabolismo , Embarazo , Nacimiento Prematuro/fisiopatología , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal , Factores de Necrosis Tumoral/genética , Factores de Necrosis Tumoral/metabolismo
10.
Virol J ; 19(1): 146, 2022 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-36096810

RESUMEN

BACKGROUND: The evaluation of human papillomavirus (HPV) prevalence rate dynamics and genotype distribution could support the adoption of more targeted prevention and treatment of cervical cancer. We aimed to assess the infection status and genotype characteristics of HPV among gynecological outpatients in Shanghai, China. METHODS: Clinical specimens were collected from patients attending gynaecological department of the Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and December 2019. The cervicovaginal infection of 17 high-risk genotypes and 10 low-risk genotypes were analyzed by Luminex-based multiple assays. RESULTS: The overall HPV infection rate was 18.81% (95% CI 18.31-19.30%) in Shanghai city, with high-risk, low-risk and mixed high- and low-risk HPV prevalence being 11.65% (95% CI 11.24-12.06%), 4.19% (95% CI 3.94-4.44%) and 2.96% (95% CI 2.74-3.17%), respectively. The five most prevalent high-risk genotypes were HPV-52 (2.95%), HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). The most common low-risk genotype was HPV-61 (1.52%), followed by HPV-6 (1.29%) and HPV-81 (1.19%). Moreover, the coverage of HPV genotype by nonavalent vaccine was 10.42%, and non-vaccine-covered high-risk genotype was 7.70%. The 15-24 years age group demonstrated the highest HPV prevalence (43.14%), and significant differences were observed among different age groups (P < 0.001). CONCLUSIONS: This study revealed the HPV prevalence and genotype distribution among women in Shanghai city, which could serve as guidance for HPV vaccination and preventative strategies against cervical cancer in this area.


Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , China/epidemiología , Femenino , Genotipo , Humanos , Papillomaviridae/genética , Prevalencia
11.
Mar Drugs ; 20(8)2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-36005499

RESUMEN

The carotenoids, including lycopene, lutein, astaxanthin, and zeaxanthin belong to the isoprenoids, whose basic structure is made up of eight isoprene units, resulting in a C40 backbone, though some of them are only trace components in Euglena. They are essential to all photosynthetic organisms due to their superior photoprotective and antioxidant properties. Their dietary functions decrease the risk of breast, cervical, vaginal, and colorectal cancers and cardiovascular and eye diseases. Antioxidant functions of carotenoids are based on mechanisms such as quenching free radicals, mitigating damage from reactive oxidant species, and hindering lipid peroxidation. With the development of carotenoid studies, their distribution, functions, and composition have been identified in microalgae and higher plants. Although bleached or achlorophyllous mutants of Euglena were among the earliest carotenoid-related microalgae under investigation, current knowledge on the composition and biosynthesis of these compounds in Euglena is still elusive. This review aims to overview what is known about carotenoid metabolism in Euglena, focusing on the carotenoid distribution and structure, biosynthesis pathway, and accumulation in Euglena strains and mutants under environmental stresses and different culture conditions. Moreover, we also summarize the potential applications in therapy preventing carcinogenesis, cosmetic industries, food industries, and animal feed.


Asunto(s)
Microalgas , Animales , Antioxidantes/metabolismo , Carotenoides/metabolismo , Femenino , Luteína/metabolismo , Microalgas/genética , Microalgas/metabolismo , Zeaxantinas/metabolismo
12.
Reproduction ; 162(1): 11-20, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-33929340

RESUMEN

Urocortins (UCNs), belonging to corticotropin-releasing hormone (CRH) family, exert their function via CRH receptor type 1 (CRHR1) and 2 (CRHR2). Our previous studies have demonstrated that CRH acts on CRHR1 to potentiate prostaglandins (PGs) output induced by inflammatory stimuli in myometrial cells. In the present study, we sought to investigate the effects of UCNs on prostaglandin (PG) output via CRHR2 in cultured human uterine smooth muscle cells (HUSMCs) from pregnant women at term. We found that UCN and UCN 3 treatment promoted PGE2 and PGF2α secretion in a dose-dependent manner. In contrast, UCN2 dose-dependently inhibited PGE2 and PGF2α secretion. Their effects were reversed by CRHR2 antagonist and CRHR2 siRNA. Mechanically, we showed that UCN and UCN3 suppressed cAMP production and led to Gi activation while UCN2 stimulated cAMP production and activated Gs signaling. Further, UCN and UCN3 but not UCN2 activated NF-κB and MAPK signaling pathways through Gi signaling. UCN and UCN3 stimulation of PGs secretion were dependent on Gi/adenylyl cyclase (AC)/cAMP, NF-κB and MAPK signaling pathways. UCN2 suppression of PGs output was through Gs/AC/cAMP signaling pathways. Our data suggest that UCN, UCN2 and UCN3 can finely regulate PGs secretion via CRHR2, which facilitates the functional status of the uterus during pregnancy.


Asunto(s)
Dinoprost/metabolismo , Dinoprostona/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Miometrio/metabolismo , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Urocortinas/farmacología , Útero/metabolismo , Dinoprost/genética , Femenino , Humanos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miometrio/efectos de los fármacos , Receptores de Hormona Liberadora de Corticotropina/genética , Útero/efectos de los fármacos
13.
Reproduction ; 162(6): 449-460, 2021 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-34718231

RESUMEN

The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.


Asunto(s)
Inflamasomas , Nacimiento Prematuro , Animales , Femenino , Humanos , Recién Nacido , Ratones , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Embarazo , Útero/metabolismo
14.
Med Sci Monit ; 27: e932093, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34475371

RESUMEN

BACKGROUND Reports of human papillomavirus (HPV) infection and genotype distribution in Chinese men are limited, and HPV vaccination has not yet been recommended for men in China. MATERIAL AND METHODS We retrospectively reviewed the prevalence and genotyping of male genital HPV. A total of 1227 male patients (aged 17 to 81 years) attending the dermatology and sexually transmitted disease clinics at Putuo District Center Hospital in Shanghai from 2015 to 2019 were included. Genital exfoliated specimens were obtained for detection and genotyping of 27 HPV types by Luminex-based multiplex assay. RESULTS The prevalence of any HPV was 65.5% (804/1227). The rate of multiple infection was 25.8% (317/1227). The 5 main HPV types were 6 (32.0%), 11 (23.2%), 16 (5.6%), 43 (4.3%), and 59 (4.0%). Among all detected HPV genotypes, 65.5% (875/1336) were 9-valent HPV genotypes. No significant differences were observed in the detection rate of HPV infection over 5 years (P>0.05). Age groups ≤24 years (70.7%) and ≥55 years (72.9%) showed higher infection rates, and significant differences were detected in rates of low-risk HPV infection in different age-stratified groups (P<0.05). Prevalence of HPV infection among patients with warts (74.4%) was significantly higher than that of patients with other clinical characteristics (40.4%) and physical examination (63.6%). CONCLUSIONS Our study suggested that more than half of Chinese male patients have detectable HPV infections, and penis-genital and anogenital warts were the most common clinical manifestations. Moreover, the available 9-valent HPV vaccine covers the most frequently observed HPV types among men.


Asunto(s)
Enfermedades de los Genitales Masculinos/epidemiología , Enfermedades de los Genitales Masculinos/virología , Papillomaviridae/clasificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Prevalencia , Estudios Retrospectivos , Adulto Joven
15.
Angew Chem Int Ed Engl ; 60(22): 12597-12606, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-33763930

RESUMEN

The efficient synthesis of long, branched, and complex carbohydrates containing multiple 1,2-cis glycosidic linkages is a long-standing challenge. Here, we report a merging reagent modulation and 6-O-levulinoyl remote anchimeric assistance glycosylation strategy, which is successfully applied to the first highly stereoselective synthesis of the branched Dendrobium Huoshanense glycans and the linear Longan glycans containing up to 30 contiguous 1,2-cis glucosidic bonds. DFT calculations shed light on the origin of the much higher stereoselectivities of 1,2-cis glucosylation with 6-O-levulinoyl group than 6-O-acetyl or 6-O-benzoyl groups. Orthogonal one-pot glycosylation strategy based on glycosyl ortho-alkynylbenzoates and ortho-(1-phenylvinyl)benzoates has been demonstrated in the efficient synthesis of complex glycans, precluding such issues as aglycon transfer inherent to orthogonal one-pot synthesis based on thioglycosides.

16.
J Cell Physiol ; 235(1): 513-525, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31236964

RESUMEN

Evidence indicates that inflammatory response is significant during the physiological process of human parturition; however, the specific signaling pathway that triggers inflammation is undefined. Toll-like receptors (TLRs) are key upstream gatekeepers that control inflammatory activation before preterm delivery. Our previous study showed that TLR4 expression was significantly increased in human pregnancy tissue during preterm and term labor. Therefore, we explore whether TLR4 plays a role in term labor by initiating inflammatory responses, therefore promoting uterine activation. The results showed that expression of TLR4, interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), CC chemokine ligand 2 (CCL-2), and uterine contraction-associated proteins (CAPs) was upregulated in the human and mice term labor (TL) group compared with the not-in-labor (TNL) group, and the TLR4 level positively correlated with CAP expression. In pregnant TLR4-knockout (TLR4-/- ) mice, gestation length was extended by 8 hr compared with the wild-type group, and the expression of IL-1ß, IL-6, TNF-α, CCL-2, and CAPs was decreased in TLR4-/- mice. Furthermore, nuclear factor-κB (NF-κB) and P38MAPK activation is involved in the initiation of labor but was inhibited in TLR4-/- mice. In uterine smooth muscle cells, the expression of inflammatory cytokines and CAPs decreased when the NF-κB and P38MAPK pathway was inhibited. Our data suggest that TLR4 is a key factor in regulating the inflammatory response that drives uterine activation and delivery initiation via activating the NF-κB/P38MAPK pathway.


Asunto(s)
Sistema de Señalización de MAP Quinasas/genética , Parto/fisiología , Receptor Toll-Like 4/metabolismo , Útero/fisiología , Animales , Células Cultivadas , Quimiocina CCL2/metabolismo , Femenino , Humanos , Inflamación/inmunología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/metabolismo , Parto/inmunología , Embarazo , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
17.
J Pak Med Assoc ; 70 [Special Issue](9): 57-63, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33177729

RESUMEN

OBJECTIVE: Lung ultrasound (LUS) is a non-radiation, easy diagnostic tool for lung diseases. This study aims to explore the diagnostic value of LUS for pregnant women with community-acquired pneumonia (CAP). METHODS: Forty-five women with a pregnancy duration of over one month, admitted to the emergency department with fever, cough, and sputum between January 1 and December 31, 2014 were recruited. Chest X-ray, LUS, peripheral blood cell count, and high-sensitivity C-reactive protein examination were conducted within 24 hours after admission. The specificity, sensitivity, false positive rate, false negative rate, positive prediction ratio, negative prediction ratio, and accuracy were calculated. LUS and chest X-ray were compared by t-test. P< 0.05 was considered as statistically significant. RESULTS: The white blood cell count and the content of high-sensitivity C-reactive protein in the pneumonia group were significantly higher than that in the control group (P<0.01). There were 21 (77.8%), 25 (92.6%), 25 (92.6%), and 5 (18.5%) patients in the pneumonia group with pulmonary consolidation, increased B-line, A-line disappearance, and pulmonary pulse by LUS, respectively. There were one (5.6%) and two (11.1%) patients with increased B-line and A-line disappearance, respectively in the control group. Difference was significant (P<0.01). CAP was diagnosed with sensitivity of 92.6%, specificity of 89.5%, false positive rate of 10.5%, false negative rate of 3.8%, positive prediction ratio of 82.6%, negative prediction ratio of 94.4%, accuracy of 93.3% and t- test value of 0.862, indicating good consistency between LUS and chest X-ray. CONCLUSIONS: Pregnant women with CAP were diagnosed by LUS and chest X-ray with good consistency. LUS should be further investigated since its advantages of no-radiation and repeatability, making it more suitable.


Asunto(s)
Infecciones Comunitarias Adquiridas , Neumonía , Infecciones Comunitarias Adquiridas/diagnóstico por imagen , Femenino , Humanos , Pulmón/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Embarazo , Mujeres Embarazadas , Ultrasonografía
18.
Angew Chem Int Ed Engl ; 59(19): 7576-7584, 2020 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-32086860

RESUMEN

The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one-pot synthesis of a nona-decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α-glucosidase inhibitory activity. The synthetic strategy features: 1) several one-pot glycosylation reactions on the basis of N-phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3', second O5', final O2') toward the challenging 2,3,5-branched Araf motif, 3) the stereoselective 1,2-cis-glucosylation by reagent control, and 4) the convergent [6+6+7] one-pot coupling reaction for the final assembly of the target nona-decasaccharide. This orthogonal one-pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.


Asunto(s)
Polisacáridos/síntesis química , Psidium/química , Secuencia de Carbohidratos , Glicosilación , Indicadores y Reactivos , Estructura Molecular , Oligosacáridos/síntesis química , Estereoisomerismo
19.
Am J Pathol ; 188(1): 63-71, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29249255

RESUMEN

Chorionic NAD-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) plays a pivotal role in controlling the amount of prostaglandins in the uterus and has been implicated in the process of labor. Prior studies identified hydrogen sulfide-generating enzymes cystathionine-ß-synthetase (CBS) and cystathionine-γ-lyase (CSE) in fetal membranes. We investigated whether hydrogen sulfide is involved in the regulation of PGDH expression in the chorion during labor. The chorionic tissues were obtained from pregnant women at preterm in labor and at term in labor or not in labor at term. Levels of CSE and CBS and hydrogen sulfide production rate were down-regulated in term in labor and preterm in labor groups compared with not in labor at term group. The CBS level correlated to PGDH expression in the chorion. Hydrogen sulfide donor NaHS and precursor l-cysteine dose-dependently stimulated PGDH expression and activity in cultured chorionic trophoblasts. The effect of l-cysteine was blocked by CBS inhibitor and CBS siRNA but not by CSE inhibitor and CSE siRNA. Hydrogen sulfide treatment suppressed miR-26b and miR-199a expression in chorionic trophoblasts. miR-26b and miR-199a mimics blocked hydrogen sulfide upregulation of PGDH expression. Our results indicate that hydrogen sulfide plays pivotal roles in maintenance of PGDH expression in the chorion during human pregnancy. Reduced expression of hydrogen sulfide-generating enzymes contributes to an increased amount of prostaglandins in the uterus during labor.


Asunto(s)
Corion/enzimología , Cistationina betasintasa/metabolismo , Cistationina gamma-Liasa/metabolismo , Hidroxiprostaglandina Deshidrogenasas/metabolismo , Trabajo de Parto Prematuro/metabolismo , Nacimiento a Término/metabolismo , Cistationina gamma-Liasa/genética , Regulación hacia Abajo , Femenino , Humanos , Sulfuro de Hidrógeno/metabolismo , Hidroxiprostaglandina Deshidrogenasas/genética , Trabajo de Parto Prematuro/genética , Embarazo , Nacimiento a Término/genética
20.
Environ Microbiol ; 20(8): 3042-3056, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29968383

RESUMEN

The unicellular Labyrinthulomycete protists have long been considered to play a significant role in ocean carbon cycling. However, their distribution and biogeochemical function remain poorly understood. We present a large-scale study of their spatiotemporal abundance and diversity in the coastal waters of Bohai Sea using flow cytometry and high-throughput sequencing. These protists display niche preferences and episodic higher biomass than that of bacterioplankton with much phylogenetic diversity (> 4000 OTUs) ever reported. They were ubiquitous with a typical abundance range of 100-1000 cells ml-1 and biomass range of 0.06-574.59 µg C L-1 . The observed spatiotemporal abundance variations support the current 'left-over scavengers' nutritional model and highlight these protists as a significant component of the marine microbial loop. The higher average abundance and phylogenetic diversity in the nearshore compared with those in the offshore reveal their predominant role in the terrigenous matter decomposition. Furthermore, the differential relationship of the protist genera to environmental conditions together with their co-occurrence network suggests their unique substrate preferences and niche partitioning. With few subnetworks and possible keystone species, their network topology indicates community resilience and high connectance level of few operational taxonomic units (OTUs). We demonstrate the significant contribution of these protists to the secondary production and nutrient cycling in the coastal waters. As secondary producers, their role will become more important with increasingly coastal eutrophication.


Asunto(s)
Eucariontes/clasificación , Eucariontes/aislamiento & purificación , Agua de Mar/parasitología , Biodiversidad , Biomasa , Eucariontes/genética , Eucariontes/crecimiento & desarrollo , Océanos y Mares , Filogenia
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