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1.
Dev Biol ; 504: 49-57, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37741309

RESUMO

SAM and SH3 domain-containing 1 (SASH1), a member of the SLy protein family, is a tumor suppressor gene that has been studied for its association with various cancers. SASH1 is highly expressed in the mammalian central nervous system, particularly in glial cells, and is expressed in the central nervous system during zebrafish embryo development. However, SASH1's role in brain development has rarely been investigated. In this study, Morpholino oligonucleotides (MO) were used to down-regulate sash1a expression in zebrafish to observe morphological changes in the brain. Three transgenic zebrafish lines, Tg(gfap:eGFP), Tg(hb9:eGFP), and Tg(coro1a:eGFP) were selected to observe changes in glial cells, neurons, and immune cells after sash1a knockdown. Our results showed that the number of microglia residing in the developmental brain was reduced, whereas the axonal growth of caudal primary motor neurons was unaffected by sash1a downregulation. And more significantly, the gfap + glia presented abnormal arrangements and disordered orientations in sash1a morphants. The similar phenotype was verified in the mutation induced by the injection of cas9 mRNA and sash1a sgRNA. We further performed behavioral experiments in zebrafish larvae that had been injected with sash1a MO at one-cell stage, and found them exhibiting abnormal behavior trajectories. Moreover, injecting the human SASH1 mRNA rescued these phenomena in sash1a MO zebrafish. In summary, our study revealed that the downregulation of SASH1 leads to malformations in the embryonic brain and disorganization of glial cell marshalling, suggesting that SASH1 plays an important role in the migration of glial cells during embryonic brain development.


Assuntos
Proteínas Supressoras de Tumor , Peixe-Zebra , Animais , Humanos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , RNA Guia de Sistemas CRISPR-Cas , Sistema Nervoso Central/metabolismo , Movimento Celular/genética , RNA Mensageiro , Mamíferos/metabolismo
2.
Pharmacol Res ; 203: 107185, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615875

RESUMO

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Animais , Microbioma Gastrointestinal , Microbiota , Imunoterapia/métodos
3.
Cell Biol Int ; 47(11): 1843-1853, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37529875

RESUMO

Thyroid cancer is a prevalent form of endocrine cancer, and its global incidence has been steadily increasing. MEX3A is a protein that is known to be highly expressed in various human malignant tumors, including thyroid cancer, and it has been linked to patient prognosis. However, the molecular mechanisms underlying MEX3A's tumorigenic capabilities in thyroid cancer are not fully understood. In this study, we aimed to investigate the role of MEX3A in thyroid cancer. We confirmed that MEX3A was overexpressed in both thyroid cancer tissues and cell lines. Additionally, we found a positive correlation between high levels of MEX3A and the AJCC stage. To further understand the functional significance of MEX3A in thyroid cancer, we depleted MEX3A expression in B-CPAP and TPC-1 cells. Interestingly, we observed a significant reduction in thyroid cancer cell proliferation and migration, as well as ameliorated cell apoptosis and arrested tumor growth upon MEX3A depletion. These findings strongly suggested that MEX3A played a critical role in the development of thyroid cancer. Furthermore, our study uncovered an important interaction between MEX3A and CREB1 (cAMP response element-binding protein 1). The interaction between MEX3A and CREB1 appeared to contribute to the tumor-promoting effects of MEX3A in thyroid cancer by directly targeting CREB1. Silencing CREB1 was observed to alleviate the malignant phenotypes promoted by MEX3A in thyroid cancer cells. Together, this study highlighted the importance of the MEX3A-CREB1 interaction in thyroid cancer development and suggested the therapeutic potential of targeting MEX3A for the treatment of this disease.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação Neoplásica da Expressão Gênica , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo
4.
J Formos Med Assoc ; 122(11): 1213-1218, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37451959

RESUMO

Since government-provided annual cervical cytology testing for all Taiwanese women aged 30 years or older became available in 1995, both cervical cancer incidence and death have decreased significantly. However, with the 2018 introduction of the national immunization program for human papillomavirus (HPV) vaccination in all schoolgirls aged 13-15 years old, the positive predictive value of cytology testing is expected to decrease with rising vaccination rates, and therefore a transition to more sensitive HPV-based testing may be needed. This position paper, derived from discussions by a panel of experts in cervical cancer screening, provides short-, medium-, and long-term policy recommendations to manage the transition between cervical screening methods for Taiwan. The recommendations include concrete suggestions regarding testing procedures, standards, accreditation, monitoring, promotion, and implementation. It is hoped that comprehensive preparation and management of this transition will enable Taiwan to repeat the previous successes of the cervical cytology testing program.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Adolescente , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Taiwan , Esfregaço Vaginal , Programas de Rastreamento , Políticas
5.
J Cell Mol Med ; 26(16): 4479-4491, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35808901

RESUMO

Venous calcification has been observed in post-thrombotic syndrome (PTS) patients; yet, the cell types and possible mechanisms regulating this process are still unclear. We evaluated the calcium deposition within the venous wall, the cell type involved in the calcified remodelling of the venous wall after thrombosis and explored possible mechanisms in vitro. Calcium deposition was found in human specimens of superficial thrombotic veins and was co-localized with VSMCs markers αSMA and TAGLN (also known as SM22α). Besides, the expression of osteogenesis-related genes was dramatically changed in superficial thrombotic veins. Moreover, the inhibition of the TGFß signalling pathway after TNFα treatment effectively induced the expression of osteogenic phenotype markers, the calcium salt deposits and the obvious phosphorylation of ERK1/2 and JNK2 in the VSMCs calcification model. Supplementing TGFß2 or blocking the activation of the ERK/MAPK signalling pathway prevented the transformation of VSMCs into osteoblast-like cells in vitro. Taken together, VSMCs have an important role in venous calcification after thrombosis. Supplementing TGFß2 or inhibiting the ERK/MAPK signalling pathway can reduce the appearance of VSMCs osteogenic phenotype. Our findings may present a novel therapeutic approach to prevent of vascular calcification after venous thrombosis.


Assuntos
Calcificação Vascular , Trombose Venosa , Cálcio/metabolismo , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Osteogênese/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Calcificação Vascular/metabolismo , Trombose Venosa/genética , Trombose Venosa/metabolismo
6.
Eur Radiol ; 32(11): 7854-7864, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35583711

RESUMO

OBJECTIVE: This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions. METHODS: This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart. RESULTS: Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s). CONCLUSIONS: The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time. KEY POINTS: • Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. • Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.


Assuntos
Doenças dos Anexos , Neoplasias Ovarianas , Humanos , Feminino , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/patologia , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Ultrassonografia , Anexos Uterinos/patologia , Sensibilidade e Especificidade
7.
Curr Microbiol ; 79(7): 193, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579721

RESUMO

Based on entire genome sequencing, this study focused on the classification of Aspergillus niger aggregation species and investigated their potential for fumonisin B2 (FB2) and ochratoxin A (OTA) production. In the current study, 22 strains were used, namely 17 A. niger strains, four A. welwitschiae strains, and one A. lacticoffeatus (a synonym of A. niger) strain. Traditional multigene phylogenetic analysis, average nucleotide identity analysis (ANI), and the whole-genome single-nucleotide polymorphism (SNP) analyses were used to reconfirm the taxonomic status of A. niger, A. welwitschiae, and A. lacticoffeatus. The ability of A. niger to produce FB2 and OTA on five culture substrates was determined, and the association between FB2 and OTA gene clusters and toxin-producing abilities was explored. The results revealed that the ANI method could distinguish A. niger from A. welwitschiae, with an ANI value of < 98%. The SNP-based phylogenetic analysis suggested that A. niger and A. welwitschiae were two independent phylogenetic species. The ANI, SNP, and multigene phylogenetic analysis supported previous findings that A. lacticoffeatus was a synonymous species of A. niger. Aspergillus niger strains exhibited the varied potential of producing FB2 and OTA on different culture media. The A. niger genome sequence analysis revealed no significant difference in fumonisin gene clusters between FB2-nonproducing isolates and FB2-producing isolates, and the integrity of the ochratoxin biosynthesis genes cluster was clearly associated with OTA production. In conclusion, gene sequencing can be useful in assessing A. niger's ability to produce OTA, but it cannot reliably predict its ability to produce FB2.


Assuntos
Fumonisinas , Ocratoxinas , Aspergillus , Aspergillus niger , Filogenia , Polimorfismo de Nucleotídeo Único
8.
J Minim Invasive Gynecol ; 29(5): 602-612, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123042

RESUMO

OBJECTIVE: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. DATA SOURCES: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence. TABULATION, INTEGRATION, AND RESULTS: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls. CONCLUSION: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.


Assuntos
Endometriose , Anticoncepcionais Orais Combinados/uso terapêutico , Endometriose/tratamento farmacológico , Endometriose/prevenção & controle , Endometriose/cirurgia , Feminino , Humanos , Metanálise em Rede , Ovariectomia , Período Pós-Operatório
9.
J Minim Invasive Gynecol ; 29(4): 519-527, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34902596

RESUMO

STUDY OBJECTIVE: To compare the safety, efficacy, and adverse events of the new mini-adjustable sling system "I-stop-mini" with transobturator midurethral slings "Obtryx" (Boston Scientific, Marlborough, MA) in women with stress urinary incontinence. DESIGN: A single-center, retrospective cohort study. SETTING: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan. PATIENTS: A total of 347 patients who underwent I-stop-mini or Obtryx for stress urinary incontinence treatment. INTERVENTIONS: Midurethral sling with either I-stop-mini or Obtryx. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were objective success and subjective cure rates between the 2 groups. Objective success was evaluated using a 1-hour pad test, and subjective cure was evaluated using a questionnaire score (Incontinence Impact Questionnaire, Urinary Distress Inventory, and International Consultation on Incontinence Questionnaire Short Form). Secondary outcomes were the evaluation of surgical outcomes, operative data, and adverse events between the 2 groups. In total, 171 of 200 I-stop-mini subjects and 127 of 147 Obtryx subjects completed 12 months of follow-up. Regarding the objective success between the I-stop-mini group and the Obtryx group, 1-month postoperative (3.6 ± 5.2 vs 3.9 ± 12.6; p = .765), 6-month postoperative (3.9 ± 5.1 vs 4.2 ± 12.6; p = .848), and 12-month postoperative (4.6 ± 5.6 vs 4.5 ± 13.6; p = .980) 1-hour pad tests showed no significant difference. The 12-month subjective cure rates decreased from 94.7% (1-month postoperative) to 91.2% (12-month postoperative) in the I-stop-mini group and 95.2% (1-month postoperative) to 85.0% (12-month postoperative) in the Obtryx group. Similar and durable efficacy was observed between the 2 groups. The I-stop-mini group had shorter operative times and hospital stays than the Obtryx group; however, both groups showed similar adverse event rates. CONCLUSION: The objective success and subjective cure rates of I-stop-mini did not differ to those of Obtryx. However, long-term data and further prospective studies on I-stop-mini are necessary to arrive at a definite conclusion.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Feminino , Seguimentos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Slings Suburetrais/efeitos adversos , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgia
10.
Proc Natl Acad Sci U S A ; 116(46): 23264-23273, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31662475

RESUMO

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Fosfoglicerato Mutase/antagonistas & inibidores , Regulação Alostérica , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos Nus , Camundongos SCID , Estrutura Molecular , Terapia de Alvo Molecular , Transplante de Neoplasias , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos
11.
J Asian Nat Prod Res ; 24(1): 24-30, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33502261

RESUMO

Phytochemical investigation on the 80% EtOH extract of the whole plants of Zephyranthes grandiflora afforded three new 4a-epi-plicamine-type alkaloids, zephyranthines A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against six glioma cell lines (CHG-5, SH-SY5Y, SHG-44, U251, U343, and GL15). Alkaloids 2 and 3 exhibited significant cytotoxic activities against all tested cell lines with IC50 values of less than 20 µM.


Assuntos
Alcaloides , Amaryllidaceae , Alcaloides/farmacologia , Linhagem Celular Tumoral , Compostos Heterocíclicos de 4 ou mais Anéis , Estrutura Molecular
12.
J Am Chem Soc ; 143(27): 10374-10381, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34191506

RESUMO

Allenone has been identified as a highly effective peptide coupling reagent for the first time. The peptide bond was formed with an α-carbonyl vinyl ester as the key intermediate, the formation and subsequent aminolysis of which proceed spontaneously in a racemization-/epimerization-free manner. The allenone coupling reagent not only is effective for the synthesis of simple amides and dipeptides but is also amenable to peptide fragment condensation and solid-phase peptide synthesis (SPPS). The robustness of the allenone-mediated peptide bond formation was showcased incisively by the synthesis of carfilzomib, which involved a rare racemization-/epimerization-free N to C peptide elongation strategy. Furthermore, the successful synthesis of the model difficult peptide ACP (65-74) on a solid support suggested that this method was compatible with SPPS. This method combines the advantages of conventional active esters and coupling reagents, while overcoming the disadvantages of both strategies. Thus, this allenone-mediated peptide bond formation strategy represents a disruptive innovation in peptide synthesis.


Assuntos
Alcenos/química , Dipeptídeos/síntese química , Oligopeptídeos/síntese química , Catálise , Dipeptídeos/química , Ligação de Hidrogênio , Conformação Proteica
13.
Int J Med Sci ; 18(7): 1600-1608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746576

RESUMO

Background: Luteal-phase ovarian stimulation (LPOS) is an alternative in vitro fertilization (IVF) protocol. However, limited data showed the genes expression of cumulus cells (CCs) in LPOS. Therefore, this study aimed to investigate CC genes expression between LPOS and follicular-phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing IVF cycles. Methods: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: NCT03238833). A total of 36 PORs who met the Bologna criteria and underwent IVF cycles were enrolled. Fifteen PORs were allocated to the LPOS group, and 21 PORs were allocated to the FPOS group. The levels of CC genes involved in inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR and compared between the two groups. Results: The number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos and top-quality day-3 embryos, clinical pregnancy rates and live birth rates were similar between the two groups except for significantly high progesterone levels in the LPOS group. The mRNA expression levels of CXCL1 (0.51 vs 1.00, p < 0.001) and PTGES (0.30 vs 1.00, p < 0.01) were significantly lower in the LPOS group than in the FPOS group. The LPOS group had significantly lower mRNA expression of NDUFB7 (0.12 vs 1.00, p < 0.001) and NDUFA4L2 (0.33 vs 1.00, p < 0.01) than the FPOS group. DAPK3 (3.81 vs 1.00, p < 0.05) and BCL6B (2.59 vs 1.00, p < 0.01) mRNA expression was significantly higher in the LPOS group than in the FPOS group. Increased expression of PCK1 (3.13 vs. 1.00, p < 0.001) and decreased expression of LDHC (0.12 vs. 1.00, p < 0.001) were observed in the LPOS group compared to the FPOS group. Conclusions: Our data revealed different CC genes expression involving in inflammation, oxidative phosphorylation, apoptosis and metabolism between LPOS and FPOS in PORs. However, the results are non-conclusive; further large-scale randomized controlled trials are needed to validate the results.


Assuntos
Células do Cúmulo/metabolismo , Fertilização in vitro/métodos , Fase Luteal/fisiologia , Indução da Ovulação/métodos , Adulto , Células do Cúmulo/efeitos dos fármacos , Feminino , Fertilização in vitro/estatística & dados numéricos , Hormônio Foliculoestimulante/administração & dosagem , Fase Folicular/efeitos dos fármacos , Fase Folicular/fisiologia , Perfilação da Expressão Gênica , Humanos , Infertilidade/terapia , Nascido Vivo , Fase Luteal/efeitos dos fármacos , Hormônio Luteinizante/administração & dosagem , Recuperação de Oócitos/estatística & dados numéricos , Indução da Ovulação/estatística & dados numéricos , Projetos Piloto , Gravidez , Taxa de Gravidez , Estudos Prospectivos , RNA Mensageiro/metabolismo , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento
14.
J Sep Sci ; 44(3): 709-716, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33245598

RESUMO

A fast and convenient high-performance liquid chromatography-electrospray ionization-ion mobility spectrometry method was developed to determine nine representative metabolites in the seedlings of cucumber and wheat. The analytical conditions were obtained by optimizing the parameters of high-performance liquid chromatography and ion mobility spectrometry. Briefly, acetonitrile-0.1% formic acid solution was selected as the mobile phase for gradient elution at a flow velocity of 0.4 mL/min. Under negative electrospray ionization mode, spray voltage of ion mobility spectrometry was 4.5 kV, and drift tube temperature was set at 90°C. The metabolites from seedling leaves were extracted using 80% acetonitrile as the solvent at 4°C for 12 h. Results showed that under soilless culture conditions, the contents of maltose, citric acid, and p-hydroxybenzoic acid in the seedlings of cucumber and wheat were reduced by low concentration of itaconic acid, succinic acid, and citric acid. Importantly, this analytical approach demonstrated high sensitivity, good linear response, and high selectivity. The lowest limit of detection was 0.004 µg for p-hydroxybenzoic acid. Overall, this high-performance liquid chromatography-electrospray ionization-ion mobility spectrometry method is sensitive and efficient for rapid separation and identification of plant metabolites.


Assuntos
Cucumis sativus/química , Plântula/química , Triticum/química , Cromatografia Líquida de Alta Pressão , Ácido Cítrico/análise , Ácido Cítrico/metabolismo , Cucumis sativus/metabolismo , Giberelinas/análise , Giberelinas/metabolismo , Malatos/análise , Malatos/metabolismo , Maltose/análise , Maltose/metabolismo , Parabenos/análise , Parabenos/metabolismo , Quercetina/análise , Quercetina/metabolismo , Plântula/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Ácido Succínico/análise , Ácido Succínico/metabolismo , Sacarose/análise , Sacarose/metabolismo , Triticum/metabolismo , Vitamina B 6/análise , Vitamina B 6/metabolismo
15.
Nucleic Acids Res ; 47(4): 2011-2028, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30517713

RESUMO

Although several studies indicate that RNA-binding proteins (RBPs) contribute to key steps in a variety of physiological processes and cancer, the detailed biological functions and mechanisms remain to be determined. By performing bioinformatics analysis using well-established hepatocellular carcinoma (HCC) datasets, we identified a set of HCC progression-associated RBPs (HPARBPs) and found that the global expression of HPARBPs was significantly correlated with patient prognosis. Among the 42 HPARBPs, human ribosomal protein S3 (RPS3) was one of the most abundant genes whose role remains uncharacterized in HCC. Gain- and loss-of-function analyses demonstrated that RPS3 promoted HCC tumorigenesis both in vitro and in vivo. Mechanistically, we revealed that silent information regulator 1 (SIRT1) was a critical target of RPS3 and was essential for sustaining the RPS3-induced malignant phenotypes of HCC cells. RPS3 stabilized SIRT1 mRNA by binding to AUUUA motifs in the 3448-3530 region of the 3' untranslated region (UTR) of SIRT1 mRNA. In addition, we found that (5-formylfuran-2-yl) methyl 4-hydroxy-2-methylenebutanoate (FMHM) inhibited HCC progression by repressing the RPS3/SIRT1 pathway. Our study unveils a novel extra-ribosomal role of RPS3 in facilitating hepatocarcinogenesis via the post-transcriptional regulation of SIRT1 expression and proposes that the RPS3/SIRT1 pathway serves as a potential therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Ribossômicas/genética , Sirtuína 1/genética , Animais , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Prognóstico , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/genética , Ativação Transcricional/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068335

RESUMO

Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman's syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate-carboxymethylcellulose or polyethylene oxide-sodium carboxymethylcellulose as anti-adhesive barrier.


Assuntos
Endométrio/patologia , Doenças Uterinas/prevenção & controle , Útero/patologia , Feminino , Humanos , Gravidez , Prevenção Primária , Aderências Teciduais , Doenças Uterinas/etiologia , Doenças Uterinas/patologia
17.
Int J Mol Sci ; 23(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35008567

RESUMO

Polycystic ovary syndrome (PCOS), which affects 5-10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine-cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.


Assuntos
Cisteína/metabolismo , Letrozol/farmacologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Receptores CCR5/metabolismo , Receptores de Quimiocinas/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diestro/efeitos dos fármacos , Diestro/metabolismo , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Glucose/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Ovário/metabolismo , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Testosterona/metabolismo
18.
Water Sci Technol ; 84(12): 3726-3737, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34928839

RESUMO

An acid modified approach to enhance the adsorption capacity of low-rank coal (lignite) is proposed to reduce the risk of heavy metal ions within the wastewater. Adsorption kinetics, adsorption thermodynamics, adsorption coefficient and density functional theory DFT calculations were studied in this paper, respectively. The results indicate that the adsorption capacity of lignite was enlarged after HNO3 modification, and pseudo-second order kinetics model and Langmuir isothermal adsorption model can be used to describe the adsorption process. The surface chemical properties of lignite play a dominant role rather than the specific surface area and total pore volume in the Pb(II) cation adsorption process, and it is suggested that the adsorption of Pb(II) cation by raw lignite (RL) and modified lignite (ML) is mainly completed by chemical adsorption. The Fourier transform infrared spectroscopy (FTIR) characterization showed that the surface oxygen functional groups of lignite increased after modification. The results of interaction energies between the model molecule and Pb(II) cation show that Pb(II) cation and -C-O-C are most easily combined, followed by -COOH, and -C = O is the weakest.


Assuntos
Carvão Mineral , Metais Pesados , Adsorção , Cátions , Chumbo
19.
Gynecol Endocrinol ; 36(8): 734-738, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31928249

RESUMO

Recurrent implantation failure (RIF) remains a clinical dilemma. Helium-Neon (He-Ne) laser irradiation has recently become more popular under certain clinical conditions. Given the unique therapeutic effects, we were interested in determining whether pretreatment with He-Ne laser irradiation prior to frozen-thawed embryo transfer (FET) would improve the microcirculation and cause the release of growth factors and cytokines, thus improving endometrial receptivity and the clinical pregnancy rates. Patients chose for themselves whether to proceed with (n = 29) or without (n = 31) pretreatment with He-Ne laser irradiation prior to FET. The clinical pregnancy rate (37.9%) and implantation rate (20.3%) were higher in the laser-treatment group than in the control group (35.5% and 15.9%, respectively, p = .844 and .518, respectively). The live birth rate was higher in the laser-treatment group (27.6% vs. 25.8%, respectively, p = .876) and the miscarriage rate was lower in the laser-treatment group (18.2% and 27.3%, respectively, p = .611). No side effects or complications from laser irradiation were encountered in patients who received the laser treatment. We concluded that pretreatment with He-Ne laser prior to FET may be an alternative choice for RIF-affected women; however, additional well-designed prospective studies are necessary to determine the precise clinical value of this treatment.


Assuntos
Aborto Habitual/radioterapia , Transferência Embrionária , Endométrio/efeitos da radiação , Lasers de Gás/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Aborto Habitual/terapia , Adulto , Blastocisto , Terapia Combinada , Implantação do Embrião/fisiologia , Implantação do Embrião/efeitos da radiação , Transferência Embrionária/métodos , Endométrio/irrigação sanguínea , Feminino , Congelamento , Humanos , Infertilidade Feminina/radioterapia , Infertilidade Feminina/terapia , Gravidez , Taxa de Gravidez , Resultado do Tratamento
20.
Sensors (Basel) ; 20(18)2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899498

RESUMO

Well-focused and accurately scaled high-resolution inverse synthetic aperture radar (ISAR) images provide a sound basis for feature extraction and target recognition. This paper proposes a novel high-resolution ISAR imaging algorithm, namely modified joint range spatial-variant autofocus and azimuth scaling algorithm (MJAAS). After motion compensation, the shift of the equivalent rotational center (ERC) of the target destroys the linear relationship between the azimuth chirp rates (ACR) of echo signals and the range coordinates of scattering points, thereby leading to the failure of azimuth scaling. Accordingly, a new joint equivalent rotational center position and effective rotational velocity (JERCP-ERV) signal model is established, serving as the basis of MJAAS. By recourse to the Davidon-Fletcher-Powell (DFP) algorithm, MJAAS can jointly estimate the ERCP and ERV by solving a minimum entropy optimization problem, so as to simultaneously achieve accurate azimuth scaling and range spatial-variant autofocus, which further improves the image focusing performance. MJAAS is not restricted by the modes of motion errors (coherent or non-coherent) and the motion compensation methods, so it can be widely applied to real data with the advantages of strong practicality and high accuracy. Extensive experimental results based on both simulated and real data are provided to corroborate the effectiveness of the proposed algorithm.

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