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1.
J Virol ; : e0091124, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240112

RESUMO

2C is a highly conserved picornaviral non-structural protein with ATPase activity and plays a multifunctional role in the viral life cycle as a promising target for anti-picornavirus drug development. While the structure-function of enteroviral 2Cs have been well studied, cardioviral 2Cs remain largely uncharacterized. Here, an endogenous ATP molecule was identified in the crystal structure of 2C from encephalomyocarditis virus (EMCV, Cardiovirus A). The ATP is bound into the ATPase active site with a unique compact conformation. Notably, the γ-phosphate of ATP directly interacts with Arg311 (conserved in cardioviral 2Cs), and its mutation significantly inhibits the ATPase activity. Unexpectedly, this mutation remarkably promotes 2C self-oligomerization and viral replication efficiency. Molecular dynamic simulations showed that the Arg311 side chain is highly dynamic, indicating it may function as a switch between the activation state and the inhibition state of ATPase activity. A hexameric ring model of EMCV 2C full length indicated that the C-terminal helix may get close to the N-terminal amphipathic helices to form a continuous positive region for RNA binding. The RNA-binding studies of EMCV 2C revealed that the RNA length is closely associated with the RNA-binding affinities and indicated that the substrate may wrap around the outer surface of the hexamer. Our studies provide a biochemical framework to guide the characterization of EMCV 2C and the essential role of arginine in cardioviral 2C functions. IMPORTANCE: Encephalomyocarditis virus (Cardiovirus A) is the causative agent of the homonymous disease, which may induce myocarditis, encephalitis, and reproductive disorders in various mammals. 2C protein is functionally indispensable and a promising target for drug development involving broad-spectrum picornaviral inhibitors. Here, an endogenous ATP molecule with a unique conformation was discovered by a combination of protein crystallography and high-performance liquid chromatography in the encephalomyocarditis virus (EMCV) 2C structure. Biochemical and structural characterization analysis of EMCV 2C revealed the critical role of conserved Arg311 in ATPase activity and self-oligomerization of EMCV 2C. The viral replication kinetics and infectivity study suggested that the residue negatively regulated the infectivity titer and virus encapsulation efficiency of EMCV and is, therefore, crucial for 2C protein to promote viral replication. Our systemic structure-function analysis provides unique insights into the function and regulation mechanism of cardioviral 2C protein.

2.
Reprod Biol Endocrinol ; 22(1): 98, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107809

RESUMO

BACKGROUND: At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear. METHODS: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation. RESULTS: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation. CONCLUSIONS: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS. TRIAL REGISTRATION: Not applicable.


Assuntos
Quimiocina CXCL10 , Células da Granulosa , Liraglutida , Folículo Ovariano , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Humanos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Animais , Camundongos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Adulto , Ovulação/efeitos dos fármacos , Líquido Folicular/metabolismo , Células Cultivadas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico
3.
Surg Endosc ; 38(7): 3828-3837, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38822144

RESUMO

BACKGROUND: No consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection. METHODS: In total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated. RESULTS: The independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0 cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0 cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively. CONCLUSIONS: LPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0 cm), TG with LPLN dissection is prioritized for clinical recommendation.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Gastrectomia , Excisão de Linfonodo , Metástase Linfática , Neoplasias Gástricas , Humanos , Junção Esofagogástrica/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Risco , Gastrectomia/métodos , Idoso , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Adulto , Linfonodos/patologia , Relevância Clínica
4.
J Proteome Res ; 22(11): 3559-3569, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37793102

RESUMO

Anastomotic leakage (AL), one of the most severe complications in rectal surgery, is often diagnosed late because of the low specificity of the clinical symptoms and limitations of current clinical investigations. Identification of patients with early AL remains challenging. Here, we explored the protein expression profiles of AL patients to provide potential biomarkers to identify AL in patients who undergo surgery for rectal cancer. We screened differentially expressed proteins (DEPs) in drainage fluid from AL and non-AL patients using a tandem mass tag method. A total of 248 DEPs, including 98 upregulated and 150 downregulated proteins, were identified between AL and non-AL groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that DEPs were enriched in neutrophil degranulation, bacterial infection, proteolysis, hemostasis, and complement and coagulation cascades. The results of enzyme-linked immunosorbent assay validated that the expression of the top three upregulated DEPs, AMY2A, RETN, and CELA3A, was significantly increased in the drainage fluid of AL patients, compared with that of non-AL patients (AMY2A, P = 0.001; RETN, P < 0.0001; and CELA3A, P = 0.023). Thus, our findings provide several potential biomarkers for the early diagnosis of AL after rectal cancer resection.


Assuntos
Fístula Anastomótica , Neoplasias Retais , Humanos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Proteômica , Detecção Precoce de Câncer , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Drenagem/efeitos adversos , Drenagem/métodos , Biomarcadores
5.
J Virol ; 96(14): e0055722, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35862702

RESUMO

Baculoviruses have been used as biopesticides for the control of Lepidoptera larvae. However, solar UV radiation reduces the activity of baculovirus. In this study, an UV endonuclease, Bm65, was found encoded in the genome of Bombyx mori nuclear polyhedrosis virus (BmNPV). Bm65 (the ortholog of AcMNPV orf79) was guided by a key nuclear localization signal to enter the nucleus and accumulated at UV-induced DNA damage sites. Subsequent results further showed that Bm65-mediated DNA damage repair was not the only UV damage repair pathway of BmNPV. BmNPV also used host DNA repair proteins to repair UV-induced DNA damage. In summary, these results revealed that Bm65 was very important in UV-induced DNA damage repair of BmNPV, and BmNPV repaired UV-damaged DNA through a variety of ways. IMPORTANCE Baculovirus biopesticides are environmentally friendly insecticides and specifically infect invertebrates. UV radiation from the sunlight greatly reduces the activity of baculovirus biopesticides. However, the molecular mechanisms of most baculoviruses to repair UV-induced DNA damage remain unclear. Nucleotide excision repair (NER) is a major DNA repair pathway that removes UV-induced DNA lesions. At present, there are few reports about the nucleotide excision repair pathway in viruses. Here, we showed for the first time that the baculovirus Bm65 endonuclease actually cleaved UV-damaged DNA. Meanwhile, we found that BmNPV used both viral-encoded enzymes and host DNA damage repair proteins to reverse UV-induced DNA damage. These results will provide a reference for the research of UV damage repair of other viruses.


Assuntos
Dano ao DNA , Reparo do DNA , Endonucleases , Nucleopoliedrovírus , Animais , Agentes de Controle Biológico/metabolismo , Bombyx , Dano ao DNA/efeitos da radiação , Endonucleases/genética , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/metabolismo , Raios Ultravioleta
6.
Phytother Res ; 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37010930

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid-induced triglyceride and cholesterol synthesis in HepG2 cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high-fat diet (HFD)-induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FASN), and stearoy-CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism.

7.
Mol Biol Rep ; 49(3): 1925-1934, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34860320

RESUMO

BACKGROUND: Lycium ruthenicum is an eco-economic shrub which can exist in two forms, thorny and thornless under varying soil moisture conditions. The aim of this study was to determine if the two forms of L. ruthenicum were influenced by soil water content (SWC) and to test the three-way link among SWC, occurrence of branch-thorn and DNA methylation modification. METHODS AND RESULTS: Here, pot experiment was carried out to reveal the influence of SWC on the occurrence of branch-thorn and then paraffin sections, scanning electron microscope and methylation-sensitive amplification polymorphism(MSAP) analysis were used to determine the three-way link among SWC, branch-thorn occurrence and DNA methylation. The results showed that (a) soil drought promoted the development of thorn primordium into branch-thorn and (b) branch-thorn covered axillary bud to protect it against drought and other stresses; (c) the branch-thorn occurrence response to drought was correlated with hypermethylation of CCGG sites and (d) thorny and thornless plants of a clone were distinguished successfully based on the MSAP profiles of their leaves. CONCLUSIONS: Branch-thorns of the L. ruthenicum clone, which occurred in response to drought, covered axillary buds to protect them against drought and other stresses; thorn primordium of the clone did not develop into branch-thorn under the adequate soil moisture condition. The occurrence and absence of the branch-thorns were correlated with the hyper- and hypo-methylation, respectively. We proposed that the branch-thorn plasticity might be an adjustment strategy for the environment, which seems to support the theory of "Use in, waste out".


Assuntos
Lycium , DNA , Metilação de DNA/genética , Lycium/genética , Folhas de Planta/genética , Solo , Água
8.
J Appl Microbiol ; 133(3): 1363-1377, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35475538

RESUMO

AIMS: This study aimed to explore the effect of Taohong Siwu Decoction (THSWD) on bone marrow mesenchymal stem cells (BMSCs) at the cellular level and the possible mechanism of systemic regulation of gut microbiota on fracture recovery. METHODS AND RESULTS: Cell Counting Kit-8 (CCK-8) experiments show that THSWD effectively promotes the proliferation of BMSCs. Transwell and wound healing assays show that THSWD effectively promotes the invasion and migration of BMSCs. Alizarin red staining showed that the THSWD model enhanced the osteogenic differentiation of BMSCs. Moreover, the effect of THSWD on BMSCs is time- and concentration-dependent. RT-qPCR and western blot results showed that THSWD treatment up-regulated the expression of vascular endothelial growth factor (VEGF) and focal adhesion kinase (FAK) at mRNA and protein levels, respectively. Haematoxylin-eosin and crocin O-quick green staining showed that after 14 days of THSWD treatment, the area of callus and cartilage regeneration at the fracture site increased significantly in rats with right femoral shaft fractures. Gut microbiota was changed in fractured rats, such as the abundance of Bacteroidetes and Firmicutes was increased. THSWD showed positive regulation of both to a certain extent. CONCLUSION: THSWD up-regulates VEGF and activates the FAK signalling pathway to enhance the development and differentiation of BMSCs, and systematically regulates the gut microbiota to promote fracture healing. SIGNIFICANCE AND IMPACT OF STUDY: This study provides new insights on the cellular and systemic level to understand the mechanism of THSWD in the treatment of fractures.


Assuntos
Consolidação da Fratura , Microbioma Gastrointestinal , Animais , Diferenciação Celular , Medicamentos de Ervas Chinesas , Proteína-Tirosina Quinases de Adesão Focal , Osteogênese , Ratos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/farmacologia
9.
J Appl Toxicol ; 42(10): 1628-1638, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35411558

RESUMO

Polychlorinated biphenyls (PCBs) affect multiple organs, and some of the effects are mediated by interfering with thyroid hormone (TH) signaling that regulates physiological processes in mammals. It remains unclear how PCBs affect skeletal muscle (SM). In our study, wistar rats were injected 2,3',4,4',5-pentachlorobiphenyl (PCB118) intraperitoneally at 0, 10, 100, and 1000 µg/kg/day for 13 weeks, and C2C12 myoblasts were treated PCB118 (0, 0.25, 25, and 50 nM) for 24 h or 48 h. We found that myocyte cross-sectional area (MCSA) was reduced, MyHC IIa and MyHC IIb mRNA levels significantly decreased, and muscle strength was weakened in PCB118-exposed rats. TH receptor α (TRα) and iodothyronine deiodinase type 2 (DIO2) were upregulated after PCB118 exposure both in vivo and in vitro. Transmission electron microscopy showed significant mitochondrial abnormalities in PCB118-treated rats, and the expression of mitochondrial regulators such as PTEN-induced kinase 1 (PINK1) and GTPase dynamin-related protein 1 (DRP1) were altered after PCB118 exposure. These results suggest that PCB118 could weaken muscle strength and attenuate fast-twitch fibers and fiber size of SM in rats. TH signaling, mitochondrial dynamics and mitophagy were also disturbed by PCB118, which may contribute to the alternations of SM structure and function.


Assuntos
Bifenilos Policlorados , Animais , Mamíferos , Dinâmica Mitocondrial , Fibras Musculares Esqueléticas , Músculo Esquelético , Bifenilos Policlorados/toxicidade , Ratos , Ratos Wistar , Hormônios Tireóideos/metabolismo
10.
J Shoulder Elbow Surg ; 31(8): e405-e412, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35121118

RESUMO

BACKGROUND: Brachial plexus injury (BPI) leading to palsy of the upper extremities is the most serious complication of the Woodward procedure for treatment of Sprengel deformity. Intraoperative neuromonitoring (IONM) is widely used for detecting emerging spinal cord or peripheral nerve injury during spinal and shoulder surgery. However, to date, its utilization in pediatric patients with Sprengel deformity is limited. Furthermore, it remains unclear whether IONM can help prevent BPI during surgery. The purpose of the current study was to assess the feasibility and effectiveness of IONM for early identification and prevention of nerve injury during the Woodward procedure. METHODS: We retrospectively reviewed the records of patients who underwent the Woodward procedure for Sprengel deformity at our institution between January 2017 and January 2020. IONM, including somatosensory evoked potentials (SEP) and motor evoked potentials (MEPs), was performed in all patients. Detailed IONM data were collected and analyzed. Preoperative and postoperative cosmetic appearance (according to the Cavendish classification), shoulder joint abduction function, and radiologic evaluation of the scapula were reviewed. Surgical complications were recorded. RESULTS: Forty-six patients (19 girls, 27 boys) were included (mean age, 5.1 ± 2.1 years). Both SEP and MEP (amplitude of the abductor pollicis) were successfully performed (100%). MEP alerts occurred in 3 patients (6.5%). After scapula position adjustment, signals recovered in 2 patients and remained unchanged in 1 patient-this patient exhibited postoperative motor deficits that resolved completely by 4 months recovery. The SEP amplitudes decreased in all 3 patients but did not reach the warning criteria. Forty patients were classified as grade III and 6 as grade IV in the Cavendish classification, whereas 35 patients were classified as grade II and 11 as grade III in the Rigault scale. The preoperative Cavendish grade was III (III, IV) and the postoperative Cavendish grade was I (I, II) (χ2 = 88.098, P < .001). The preoperative Rigault grade was II (II, III) and the postoperative Rigault grade was I (I, II) (χ2 = 62.133, P < .001). The mean arc of shoulder joint abduction improved from 99° ± 8° to 167° ± 7° (t = -45.871, P < .001) after surgery. Except for temporary motor deficits detected in 1 patient, no other postoperative complications were observed through the time of final follow-up. CONCLUSION: IONM during the Woodward procedure for Sprengel deformity is feasible and effective in detecting intraoperative neurologic changes and may be effective in preventing BPI associated with surgery.


Assuntos
Articulação do Ombro , Criança , Pré-Escolar , Anormalidades Congênitas , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Escápula/anormalidades , Escápula/cirurgia , Articulação do Ombro/anormalidades , Articulação do Ombro/cirurgia
11.
J Mol Struct ; 1268: 133709, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35846732

RESUMO

The rapidly evolving Coronavirus Disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide with thousands of deaths and infected cases. For the identification of effective treatments against this disease, the main protease (Mpro) of SARS­CoV­2 was found to be an attractive drug target, as it played a central role in viral replication and transcription. Here, we report the results of high-throughput molecular docking with 1,045,468 ligands' structures from 116 kinds of traditional Chinese medicine (TCM). Subsequently, 465 promising candidates were obtained, showing high binding affinities. The dynamic simulation, ADMET (absorption, distribution, metabolism, excretion and toxicity) and drug-likeness properties were further analyzed the screened docking results. Basing on these simulation results, 23 kinds of Chinese herbal extracts were employed to study their inhibitory activity for Mpro of SARS­CoV­2. Plants extracts from Forsythiae Fructus, Radix Puerariae, Radix astragali, Anemarrhenae Rhizoma showed acceptable inhibitory efficiencies, which were over 70%. The best candidate was Anemarrhenae Rhizoma, reaching 78.9%.

12.
J Sci Food Agric ; 102(14): 6539-6554, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35580061

RESUMO

BACKGROUND: Water footprint (WF) can comprehensively evaluate agricultural water use efficiency under high-temperature weather. Based on the historical meteorological data in the Huang-Huai-Hai (3H) region of China, this study used the percentile threshold method to analyze the distribution of high-temperature events and set three types of meteorological scenarios, namely the actual temperature scenario (S1), the high temperatures in the ear stage scenario (S2), and the high temperatures in the flowering-maturity stage scenario (S3). The growing degree day (GDD) mode and calendar day (CD) mode in the AquaCrop model were used to simulate the yield per unit area (Yunit ) of maize under different temperature scenarios and then the crop evapotranspiration (ETc ) and production WF during maize growth period were calculated. RESULTS: The occurrence frequency of extreme high-temperature event in ear stage in the 3H region was lower than that in the flowering-maturity stage. There were significant differences in the WF of maize between S1 and S2 and between S1 and S3 in GDD mode, and significant differences in Yunit , ETc , and WF of maize under three temperature scenarios in the CD mode. CONCLUSION: High temperature events occur in maize growth period, especially in the flowering-maturity stage, will increase the WF of maize. Measures such as changing the planting structure, changing the sowing date of maize and cultivating heat-resistant maize varieties could be taken to reduce the negative impacts of high-temperature weather. © 2022 Society of Chemical Industry.


Assuntos
Temperatura Alta , Zea mays , Agricultura/métodos , China , Temperatura , Água
13.
J Nat Prod ; 84(11): 2929-2936, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34662124

RESUMO

Nine new dolabrane-type diterpenoids, notoscarins A-I (1-9), including an unprecedented 6,18-cyclo-dolabrane-type diterpenoid (1) obtained through intramolecular cyclization, two rare 19-nor-2-chloro-dolabrane diterpenoids (2 and 3), six new related dolabrane-type diterpenoids (4-9), and one new butyrolactone derivative (10), were isolated from the Chinese liverwort Notoscyphus lutescens. The 6,18-cyclo-dolabrane and 19-nor-dolabrane carbon skeletons are reported for the first time. The structures of these compounds were determined on the basis of MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Preliminary bioassays showed that compounds 1-10 exhibited moderate to weak quinone reductase-inducing activity in Hepa-1c1c7 cells.


Assuntos
Diterpenos/isolamento & purificação , Hepatófitas/química , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Espectroscopia de Ressonância Magnética
14.
World J Surg Oncol ; 19(1): 187, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172053

RESUMO

BACKGROUND: Postoperative symptomatic anastomotic leakage (AL) is a serious complication after low anterior resection (LAR) for rectal cancer. AL can potentially affect short-term patient outcomes and long-term prognosis. This study aimed to explore the risk factors and long-term survival of symptomatic AL after laparoscopic LAR for rectal cancer. METHODS: From May 2009 to May 2015, 298 consecutive patients who underwent laparoscopic LAR for rectal cancer with or without a defunctioning stoma were included in this study. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for symptomatic AL. Survival analysis was performed using Kaplan-Meier curves, and log-rank tests were used for group comparisons. RESULTS: Among the 298 patients enrolled in this study, symptomatic AL occurred in eight (2.7%) patients. The univariate analysis showed that age of ≤65 years (P = 0.048), neoadjuvant therapy (P = 0.095), distance from the anal verge (P = 0.078), duration of operation (P = 0.001), and pathological tumor (T) category (P = 0.004) were associated with symptomatic AL. The multivariate analysis demonstrated that prolonged duration of operation (P = 0.010) was an independent risk factor for symptomatic AL after laparoscopic LAR for rectal cancer. No statistically significant differences were observed in the 3-year (P = 0.785) and 5-year (P = 0.979) overall survival rates. CONCLUSIONS: A prolonged duration of operation increased the risk of symptomatic AL after laparoscopic LAR for rectal cancer. An impact of symptomatic AL on a long-term survival was not observed in this study; however, further studies are required. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry ( ChiCTR2000033413 ) on May 31, 2020.


Assuntos
Laparoscopia , Neoplasias Retais , Idoso , Anastomose Cirúrgica , Fístula Anastomótica , Humanos , Prognóstico , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Fatores de Risco
15.
Dermatol Ther ; 33(1): e13181, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769900

RESUMO

Postherpetic neuralgia (PHN) is a debilitating disease characterized by continuous, intense pain following an outbreak of herpes zoster. The pain associated with PHN can severely affect a patient's quality of life, quality of sleep, and ability to participate in activities of daily living. The aim of this study was to explore the clinical efficacy of the subcutaneous injection of botulinum toxin-A (BTX-A) for the treatment of PHN. Thirteen patients with PHN were enrolled in this study and treated once with BTX-A. The effects of BTX-A on pain were measured with the visual analogue scale (VAS) 1, 2, 4, 8, 12, and 16 weeks after administration. Compared with pretreatment scores, VAS pain scores decreased at 2 weeks post-treatment in all patients. All patients felt varying degrees of pain relief but remained comfortable. Compared with oral analgesic drugs, VAS scores were significantly different at 2, 4, 8, 12, and 16 weeks post-treatment (p < .05). These results demonstrated that subcutaneous administration of BTX-A can decrease pain in patients with PHN.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Neuralgia Pós-Herpética/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Qualidade de Vida , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fatores de Tempo , Resultado do Tratamento
16.
Pestic Biochem Physiol ; 164: 91-99, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284142

RESUMO

Baculoviruses have been developed as long-term and environmentally friendly biopesticides. However, solar ultraviolet radiation can reduce the activity of baculovirus. Radiation sensitive 23 (Rad23) can recognize DNA damage and is involved with nucleotide excision repair (NER). In the current study, BmRad23 was accumulated mainly within the nucleus. Host cell reactivation (HCR) assays have shown that BmRad23 significantly facilitated the expression of UV-damaged mCherry reporter gene. Reverse transcription quantitative PCR (RT-qPCR) result showed that the mRNA expression level of BmRad23 was increased in (Bombyx mori nuclear polyhedrovirus, BmNPV) BmNPV-infected BmN cells. However, the expression of BmRad23 was increased significantly when BmNPV budded viruses (BVs) or BmN cells were irradiated with UV light. Overexpression of BmRad23 promoted the mRNA levels of two UV-induced DNA damage repair genes which were from Bombyx mori and BmNPV, respectively. Meanwhile, the overexpression of BmRad23 in BmN cells was conducive to the proliferation of BmNPV and UV-damaged BmNPV. The recombinant BmNPV BVs expressing BmRad23 showed stronger resistance to UV radiation than the control virus. In conclusion, the results revealed that BmRad23 contributed to the proliferation of BmNPV and the repair of UV-damaged BmNPV, which would provide a reference for the development of efficient baculovirus pesticides against UV radiation.


Assuntos
Bombyx , Nucleopoliedrovírus , Animais , Baculoviridae , Dano ao DNA , Raios Ultravioleta
17.
J Foot Ankle Surg ; 59(3): 616-624, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354519

RESUMO

Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.


Assuntos
Cistos Ósseos Aneurismáticos/cirurgia , Neoplasias Ósseas/cirurgia , Transplante Ósseo , Calcâneo/cirurgia , Condroblastoma/cirurgia , Ílio/transplante , Adulto , Cistos Ósseos Aneurismáticos/complicações , Cistos Ósseos Aneurismáticos/diagnóstico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico , Condroblastoma/complicações , Condroblastoma/diagnóstico , Feminino , Humanos , Transplante Autólogo
18.
Dermatol Ther ; 32(4): e12992, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31172649

RESUMO

Vitiligo is a disease pathologically characterized by specific damage to melanocytes. The aim of this study was to explore the mechanism underlying CO2 fractional laser treatment of vitiligo by detecting the levels of Th1 cytokines (IL-2 and IFN-γ), Th2 cytokines (IL-4 and IL-10), and Th17 cytokines (IL-17 and IL-23) in peripheral blood. Twenty five vitiligo patients were enrolled in this study and were treated with a CO2 fractional laser four to eight times. The cytokines of 25 vitiligo patients and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay. After CO2 fractional laser therapy, six cases were cured, and the apparent efficiency was 72.0% (18/25), while the efficiency was 92.0% (23/25). Before CO2 fractional laser therapy, IL-2 and IFN-γ levels in vitiligo patients were higher than those in the control group, but the difference was not statistically significant (p > .05). IL-4, IL-10, IL-17, and IL-23 levels were also higher in vitiligo patients than those in the control group (p < .05). After treatment, IL-2 and IFN-γ levels in vitiligo patients were lower than before treatment, but the difference was not statistically significant (p > .05), while IL-4, IL-10, IL-17, and IL-23 levels were significantly lower compared with before treatment (p < .05). The results show that CO2 fractional laser treatment has a good curative effect in the treatment of vitiligo.


Assuntos
Citocinas/sangue , Lasers de Gás/uso terapêutico , Vitiligo/terapia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th2/imunologia , Resultado do Tratamento , Vitiligo/sangue , Adulto Jovem
19.
Dermatol Ther ; 32(5): e13065, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31414707

RESUMO

Condyloma acuminatum (CA) is a type of mucosal benign hyperplasia skin disease that is caused by human papillomavirus (HPV) infection, which mainly occurs in the genitalia and anus. The aim of the present study was to explore the clinical efficacy underlying the traditional Chinese medicine paiteling in the treatment of CA via the detection of HPV. One hundred CA patients were enrolled in the current study and were externally treated with paiteling for 5 weeks. HPV subtypes were examined both before the treatment and at 6 months after the treatment. After the external paiteling therapy, 92 cases were cured, and the apparent efficiency was 92.0% (92/100), while 8 cases exhibited recurrence. Before the external paiteling therapy, the numbers of cases of low-risk, high-risk, and mixed types of HPV were 40, 35, and 25, respectively. At 6 months after treatment, the numbers of negative cases of low-risk, high-risk, and mixed types of HPV were 38, 32, and 20, respectively. The results demonstrated that external paiteling treatment has a good curative effect on the treatment of CA.


Assuntos
Condiloma Acuminado/tratamento farmacológico , Condiloma Acuminado/virologia , Medicamentos de Ervas Chinesas/administração & dosagem , Infecções por Papillomavirus/tratamento farmacológico , Administração Tópica , Adulto , Biópsia por Agulha , China , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Infecções por Papillomavirus/fisiopatologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
20.
BMC Musculoskelet Disord ; 20(1): 298, 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228939

RESUMO

BACKGROUND: To compare the mid-long-term clinical and radiological outcomes between a combination of cortico-cancellous iliac bone graft with vascularized greater trochanter flap (Group A) and isolate iliac bone graft (Group B) in the treatment of Osteonecrosis of the Femoral Head (ONFH). METHODS: From January 2006 to December 2012, 123 patients (135 hips) who underwent abovementioned hip-preserving surgeries were included for analysis. Clinical outcomes were assessed based on Harris Hip Score (HHS) System and The Western Ontario and McMaster University Index (WOMAC) scores between the preoperative and the last follow-up. A series of postoperative X-rays were compared to preoperative images for radiological evaluation. RESULTS: The HHS in Group A and B were enhanced from 50.57 ± 3.39 to 87.60 ± 4.15 and from 50.24 ± 3.30 to 85.18 ± 6.45, respectively, which both showed significance between preoperative and postoperative latest follow-up (p < 0.001). Group A revealed better improvement in terms of HHS (p = 0.017). The WOMAC total, postoperative stiffness, difficulty subscale scores in Group A showed better outcomes when compared to Group B (p < 0.01), while pain improvement between these two groups revealed no significance (p = 0.402). Besides, Group A suggested better necrotic region repair (p = 0.020), but no femoral head collapse difference in terms of Association Research Circulation Osseous classification change was found (p > 0.05). CONCLUSIONS: A combination of cortico-cancellous iliac bone graft and concurrent vascularized greater trochanter flap with the lateral femoral circumflex transverse branch has been proved can obtain better functional and radiological results than isolate iliac bone grafting, which is attributed to blood reconstruction of the femoral head.


Assuntos
Transplante Ósseo/métodos , Necrose da Cabeça do Fêmur/cirurgia , Fêmur/transplante , Ílio/transplante , Retalhos Cirúrgicos/transplante , Adolescente , Adulto , Osso Esponjoso/transplante , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/fisiopatologia , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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