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1.
Prev Med Rep ; 36: 102452, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37869538

RESUMO

To summarize current prevalence and drug resistance rate of Escherichia coli (E. coli) among orthopaedic surgical site infections (SSIs) in China from English and Chinese language sources. Online databases were searched to collect related researches. A meta-analysis was performed to analyse prevalence and 95 % confidence interval (CI) of E. coli among patients with orthopedic surgical site infections. Meta-regression analysis was used to investigate the difference in the prevalence and antimicrobial resistance of E. coli among different subgroups. A total of 52 studies were enrolled into our meta-analysis, with a total of 31,285 strains isolated. The overall E. coli prevalence was 13.4 % (95 % CI 11.6-15.5). Study design (R2 = 8.98) and sample size (R2 = 10.95) might be potential sources of heterogeneity and there were no significant differences in risk of bias (R2 = 0.28), study time (R2 < 0.01), region (R2 = 2.46) and hospital level (R2 = 1.42). E. coli resistance were reported in 43 of the 52 papers. Antimicrobial resistance of E. coli to Ampicillin [87.9 % (95 % CI 83.7-91.1)] before 2015 was higher than that after 2015 [80.3 % (95 % CI 75.0-84.7)] (R2 = 30.93, P = 0.033). While, resistance rate to Cefepime and Amikacin was significantly higher before 2015 (R2 = 17.25 and 6.54, P = 0.043 and 0.048), i.e., 46.4 % (36.3-56.9), 19.9 % (13.8-27.7) and 29.1 % (19.4-41.2), 8.6 % (4.4-16.2) in 2015 and after. It is necessary to carry out long-term monitoring to understand the actual prevalence and antimicrobial resistance of E. coli to develop appropriate health care mechanisms.

2.
Bioorg Chem ; 135: 106530, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37054517

RESUMO

Hepatic ischemia/reperfusion injury is a major cause of hypohepatia after surgical procedures such as hypovolemic shock, transplantation, and so on. In our continuous study of bioactive natural products from fungus, eight ergosterol-type sterides (1-8), including two undescribed compounds, sterolaspers A (1) and B (2), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and comparison with the reported NMR data as well as X-Ray single crystal diffraction tests. Activity screen of these isolates showed 5α-stigmast-3,6-dione (3) possessing anti-hypoxia injury effects against CoCl2-induced hypoxia damage in hepatocytes. More importantly, compound 3 could improve liver function, alleviate liver damage, and restrain the hepatocellular apoptosis in hepatic ischemia/reperfusion injury murine model. As such, this ergosterol-type steride, 5α-stigmast-3,6-dione (3), might serve as lead structure for the development of novel hepatoprotective agents in the clinical treatment of hepatic ischemia/reperfusion injury.


Assuntos
Fígado , Traumatismo por Reperfusão , Camundongos , Animais , Hepatócitos , Traumatismo por Reperfusão/tratamento farmacológico , Apoptose , Isquemia/complicações , Aspergillus
3.
Biomedicines ; 11(3)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36979852

RESUMO

Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT-PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.

4.
J Foot Ankle Surg ; 62(3): 583-589, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36973143

RESUMO

The research results are inconsistent that assessing whether the increased obliquity of the distal articular surface of the medial cuneiform leads to an increase in hallux valgus angle. Thus, this study investigated the relationship between distal medial cuneiform obliquity and hallux valgus by measuring various angles in weightbearing anteroposterior radiographs of the foot. In total, 679 feet of 538 patients with the radiographs were included in the study. We measured radiographic parameters including hallux valgus angle, first to second intermetatarsal angle, metatarsus adductus angle, first metatarsus cuneiform angle, distal medial cuneiform angle, and first proximal metatarsal articular angle. The surface morphology (flat or curved) of the first tarsometatarsal joint was also recorded. Our results analysis revealed a weak negative correlation between distal medial cuneiform angle and both hallux valgus angle and first to second intermetatarsal angle, contrary to our assumption. So we believe that distal medial cuneiform angle was relatively constant and it cannot be used as a characteristic angle for quantifying hallux valgus. First metatarsus cuneiform angle was a characteristic indicator of hallux valgus and was positively correlated with its severity (p < .000), indicating that it can be used to measure the size of hallux valgus. It can also be used as a reference factor for the first metatarsal osteotomy in clinical bunion orthopedics. First tarsometatarsal joint morphology was unrelated to hallux valgus, whereas metatarsus adductus angle, and first proximal metatarsal articular angle should be considered in hallux valgus.


Assuntos
Joanete , Hallux Valgus , Hallux , Ossos do Metatarso , Metatarso Varo , Humanos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Hallux/cirurgia , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Osteotomia
5.
BMC Surg ; 22(1): 217, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668407

RESUMO

BACKGROUND: For periacetabular osteotomy, traditional approaches usually have a long learning curve. We aimed to evaluate the postoperative results and complications of periacetabular osteotomy under a new double-incision approach. METHODS: The records of 58 consecutive patients (65 hips) who underwent periacetabular osteotomy using the new approach were retrospectively reviewed and evaluated. There were 52 women and 6 men with a mean age of 28.1 years at the time of surgery. RESULTS: The average follow-up period was 35.2 months, during which no patients were converted to total hip arthroplasty. Complications included 6 hips (9.2%) with nerve dysesthesias and 1 hip (1.5%) with delayed wound healing. The mean operative time and intraoperative blood loss were 88.6 min and 402.8 ml, respectively. The mean modified Harris hip score had improved from 72.2 points preoperatively to 91.3 points at the last follow-up. Fifty-five patients (62 hips, 95.4%) were satisfied to their outcomes, and good preoperative functional score was associated with a satisfactory outcome. Furthermore, the average lateral center-edge angle, anterior center-edge angle and acetabular index angle were corrected well after surgery. CONCLUSION: Periacetabular osteotomy using modified Smith-Petersen or Bikini approach with posterolateral assisted small incision can be performed safely and with satisfactory results. In addition, this technique shortens the learning curve, and reduces the operating complexity, especially for beginner.


Assuntos
Luxação Congênita de Quadril , Luxação do Quadril , Ferida Cirúrgica , Adulto , Feminino , Luxação do Quadril/etiologia , Luxação do Quadril/cirurgia , Luxação Congênita de Quadril/diagnóstico por imagem , Humanos , Masculino , Osteotomia/métodos , Radiografia , Estudos Retrospectivos , Ferida Cirúrgica/etiologia , Resultado do Tratamento
6.
Org Biomol Chem ; 20(24): 4970-4975, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35674501

RESUMO

(±)-Walskiiglucinol A (1a/1b), a pair of rearranged acylphloroglucinol derivatives with a new carbon skeleton, was obtained from Hypericum przewalskii. Compounds 1a/1b were the first examples of naturally occurring acylphloroglucinol derivatives possessing a unique 1-oxaspiro[4.4]nonane core bearing a new 5/5 ring system. Their planar and relative structures were identified by extensive spectroscopic analysis and NMR chemical shift calculations with DP4+ probability analysis, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway of 1a/1b was proposed in which the breakage of the C-2/C-3 linkage via a retro-Claisen reaction and the cyclization between C-3 and C-1 were proposed as key steps. The isolates were evaluated for cytotoxic activities against a panel of cancer cell lines and anti-inflammatory activities against lipopolysaccharide (LPS)-induced NO production, and compounds 1a/1b showed moderate cytotoxic activities with IC50 values ranging from 9.72 to 36.75 µM.


Assuntos
Antineoplásicos Fitogênicos , Hypericum , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Hypericum/química , Estrutura Molecular , Floroglucinol/química , Estereoisomerismo
7.
J Org Chem ; 87(10): 6824-6831, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35545918

RESUMO

Norprzewalsone A (1), a rearranged polyprenylated polycyclic acylphloroglucinol (PPAP) with a new carbon skeleton, along with a new congener, norprzewalsone B (2), were isolated from Hypericum przewalskii. Compound 1 possessed a new 5/6/5/6/6 pentacyclic ring system based on a spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] core, which might be derived from the common [3.3.1]-type bicyclic polyprenylated acylphloroglucinol (BPAP) via the key retro-Claisen, intramolecular cyclization, and Diels-Alder cyclization reactions. Their structures and absolute configurations were confirmed by spectroscopic data, calculated 1D NMR data with DP4+ probability analyses, and electronic circular dichroism calculations and comparison. More significantly, compound 1 exhibited a moderate inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells.


Assuntos
Hypericum , Compostos de Espiro/química , Alcanos , Ciclopentanos , Hypericum/química , Estrutura Molecular , Floroglucinol/química , Floroglucinol/farmacologia
8.
Ann Transl Med ; 10(6): 373, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35433989

RESUMO

Background and Objective: The pathogenesis of osteoarthritis (OA) involves a variety of complex mechanisms, including genetic, mechanical, metabolic, and inflammatory factors. There is evidence that inflammatory factors, abnormal chondrocyte apoptosis, and extracellular matrix degradation are closely associated with the occurrence and development of OA. The best treatment for OA is still controversial, but intra-articular injection is safer and more effective than non-surgical treatments, such as physical therapy and oral analgesics. This study sought to explore the mechanism, benefits, and adverse reactions of commonly used intra-articular injection therapy in the treatment of knee osteoarthritis (KOA). Methods: We analyzed the safety and adverse reactions of intra-articular injection in patients with KOA, and summarized the results. Key Content and Findings: Six weeks of the corticosteroid injection contributed to improve the symptoms of OA patients in short time. However, their symptoms did not improve significantly after this period. Using corticosteroids for a long time may result in oxidative stress, leading to adverse reactions, such as cartilage toxicity, and accelerate the progress of OA. Due to its high frequency, the local injection of hyaluronic acid can result in more adverse reactions when compared with the corticosteroids. Due to the lack of standardized factors for platelet-rich plasma (PRP) preparation, leukocyte-rich or leukocyte-free variants may be produced. Adverse reactions include injection-site pain, joint stiffness. Conclusions: Thus, it is necessary to promote further clinical trials to promote the clinical application of PRP.

9.
Phytochemistry ; 199: 113166, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35367463

RESUMO

Kiiacylphnols A-H, eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs), along with two known congeners (hyperforcinol F and oxepahyperforin), were obtained from Hypericum przewalskii Maxim. The structures of these metabolites were confirmed by spectroscopic analyses, quantum-chemical 1H and 13C NMR calculations with DP4+ analyses, electronic circular dichroism (ECD) comparisons and calculations. Kiiacylphnols A and B were the first [3.3.1]-type PPAPs with an unusual octahydrooxireno[2,3-i]chromene scaffold bearing a rare 6/6/6/3 ring system. More significantly, kiiacylphnol A and oxepahyperforin displayed cytotoxicity against acute myeloid leukemia and diffuse large B-cell lymphoma cell lines by inducing cell apoptosis.


Assuntos
Hypericum , Apoptose , Dicroísmo Circular , Hypericum/química , Estrutura Molecular , Floroglucinol/química , Floroglucinol/farmacologia
10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(2): 209-214, 2022 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-35172407

RESUMO

OBJECTIVE: To investigate the relationship between hallux valgus and the indicators associated with medial cuneiform obliquity measured on feet weight-bearing anteroposterior X-ray films. METHODS: Based on the feet weight-bearing anteroposterior X-ray films taken between January 2018 and February 2021 and met the criteria, the hallux valgus angle (HVA), intermetatarsal angle (IMA), metatarsus adductus angle (MAA), metatarsus cuneiform angle (MCA), distal medial cuneiform angle (DMCA), and proximal metatarsal articular angle (PMAA) were measured and the morphology of the first tarsometatarsal (TMT) were recorded. According to the HVA, the X-ray films were divided into normal group (HVA<15°) and hallux valgus group (HVA≥15°). The gender, age, sides, IMA, MAA, MCA, DMCA, PMAA, and the morphology of TMT were compared between groups. The influencing factors of HVA and IMA were analyzed by multivariate linear regression analysis. RESULTS: X-ray films of 534 patients (679 feet) met the selection criteria and were included in the study. There were 220 males and 314 females, with an average age of 36 years (mean, 18-82 years). There were 154 cases (168 feet) in the normal group and 403 cases (511 feet) in the hallux valgus group. There were significant differences in gender and age between groups ( P<0.05), and no significant difference in the side ( P>0.05). The IMA, MAA, and MCA in the hallux valgus group were significantly bigger than those in the normal group ( P<0.05); the difference in DMCA between the two groups was not significant ( P>0.05). The TMT morphology of the two groups was mainly curved, and the difference in morphology classification was not significant ( P>0.05). PMAA measurement showed that there were 3 kinds of metatarsal shapes: adductive metatarsal, neutral metatarsal, and abductive metatarsal, the difference in metatarsal shapes between groups was not significant ( P>0.05). The PMAA of abductive metatarsal was significantly bigger in normal group than in hallux valgus group ( P<0.05), there was no significant difference in PMAA of adductive metatarsal between groups ( P>0.05). Multivariate linear regression analysis showed that age, MCA, and DMCA were the influencing factors of HVA ( P<0.05), and age, MAA, MCA, and DMCA were the influencing factors of IMA ( P<0.05). CONCLUSION: The medial cuneiform obliquity is relatively constant and the DMCA can not be used as the characteristic angle to quantify hallux valgus. The morphology of TMT has no relationship with hallux valgus, while MAA, MCA, and PMAA are all factors to be considered, and MCA can be used as the characteristic angle to quantify hallux valgus.


Assuntos
Hallux Valgus , Ossos do Metatarso , Metatarso Varo , Ossos do Tarso , Adulto , Feminino , Hallux Valgus/cirurgia , Humanos , Masculino , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Radiografia
11.
Org Biomol Chem ; 20(6): 1284-1291, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35072672

RESUMO

Spihyperglucinols A (1) and B (2), the first 13,15-nor-polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring a 7/6/5 tricyclic ring system based on an unexpected bicyclo[3.2.2]nonane core, along with three new congeners, spihyperglucinols C-E (3-5), were isolated from Hypericum longistylum. Importantly, 1 and 2 displayed potential inhibitory effects on the production of nitric oxide in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with IC50 values of (8.70 ± 1.18) and (9.23 ± 1.26) µM, respectively, comparable to the positive control, dexamethasone, with an IC50 value of (9.76 ± 1.13) µM.


Assuntos
Floroglucinol
12.
Bone Joint Res ; 10(9): 558-570, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34465146

RESUMO

AIMS: Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. METHODS: High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. RESULTS: More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-ß1) was downregulated, while that of TGF-ß2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. CONCLUSION: DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558-570.

13.
Bioorg Chem ; 115: 105246, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371372

RESUMO

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperwilsones A-K (1-11), along with five known PPAPs (12-16), were isolated from Hypericum wilsonii. Their structures were established via spectroscopic methods, the careful analysis of calculated and experimental electronic circular dichroism (ECD) spectra, single-crystal X-ray diffraction, the modified Mosher's method, and [Rh2(OCOCF3)4]-induced ECD. Hyperwilsone A (1) and hyperwilsone B (2) possessed the unique acetal functionality. Hyperwilsone C (3) was a rare example of [3.3.1]-type PPAP possessing a 3-isopropylfuran moiety. In bioassay, compounds 9 and 10 showed potent anti-inflammatory activity against LPS-induced NO production by inhibiting the nuclear translocation of NF-κB p65 and thus reducing the production of proinflammatory cytokines. Compounds 5, 8, 11, and 14 exhibited moderate inhibitory activity against SUDHL-4 and HL60 cancer cells with IC50 values in the range of 5.74-19.82 µM.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Descoberta de Drogas , Hypericum/química , Floroglucinol/farmacologia , Compostos Policíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Floroglucinol/química , Floroglucinol/isolamento & purificação , Compostos Policíclicos/química , Compostos Policíclicos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-Atividade
14.
Phytochemistry ; 187: 112779, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33915420

RESUMO

Three pairs of previously undescribed 2,3-nor-monocyclic polyprenylated acylphloroglucinols (MPAPs), (±)-hyperzewalsins A-C, a pair of 1,2,3,4-nor-MPAPs, (±)-hyperzewalsins D, along with one undescribed precursor, hyperzewalsin E, were isolated and identified from the aerial parts of Hypericum przewalskii Maxim. (Hypericaceae), and their structures were confirmed by extensive spectroscopic analyses, and quantum-chemical calculations including electronic circular dichroism calculations and NMR calculations with a DP4+ analysis. Significantly, (±)-hyperzewalsins A-D represented the first nor-MPAPs bearing carbon chain constitutions based on diverse highly degraded phloroglucinols. (±)-Hyperzewalsins A-C were the rare nor-MPAPs characterized by degradations of C-2 and C-3 in the core decorated by scissions of C-3/C-4 and C-1/C-2 bonds through Retro-Claisen reactions. (±)-Hyperzewalsins D were the first examples of naturally occurring MPAPs with the loss of C-1/2/3/4 in the phloroglucinol ring formed by cleavages of C-3/C-4 and C-1/C-6 bonds via Retro-Claisen and decarboxylation reactions. Plausible biogenetic pathways for the isolates were proposed. The isolates were evaluated for their immunosuppressive activity in lipopolysaccharide-stimulated murine splenocytes.


Assuntos
Hypericum , Animais , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Floroglucinol/farmacologia
15.
J Org Chem ; 86(9): 6478-6485, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33887911

RESUMO

Hypaluton A (1), an unprecedented nor-polycyclic polyprenylated acylphloroglucinol (PPAP) bearing a new 8/6 bicyclic architecture, along with a new congener, hypaluton B (2), was obtained from Hypericum patulum. Their structures were confirmed by spectroscopic analyses, quantum-chemical 13C NMR calculations, electronic circular dichroism comparisons, and calculations. Hypaluton A is the first PPAP possessing an unparalleled 3,4-nor-bicyclic polyprenylated acylphloroglucinol (BPAP) scaffold, which might be derived from the common [5.3.1]-type-BPAP by losing seven carbons (C-3/4 of the acylphloroglucinol core and the isoprenyl at C-3) via the breakage at C-4-C-5 and C-2-C-3 bonds in the acylphloroglucinol core, together with the benzoyl migration through the hemiketalization/retro-Claisen cascade. More significantly, compound 1 is also the first discovered [6.3.0]-PPAP, which displayed pronounced inhibitory activity against lipopolysaccharide-induced B lymphocyte proliferation.


Assuntos
Hypericum , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Floroglucinol
16.
Bioorg Chem ; 111: 104902, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33894431

RESUMO

Five new 2-nor-bicyclic polyprenylated acylphloroglucinols (BPAPs), norhyperpalums A-E (1-5), three new 2,3-nor-BPAPs, norhyperpalums F-H (8-10), one new 2,3,4-nor-BPAP (13), and four known analogs (6, 7, 11 and 12) were obtained from Hypericum patulum. Their structures were confirmed by spectroscopic data, electronic circular dichroism (ECD) calculations and comparisons, quantum-chemical 13C NMR calculations with DP4 + probability analysis, the modified Mosher's method, Rh2(OCOCF3)4-induced ECD, and X-ray crystallographic data. Norhyperpalums A-E (1-5) are rare 2-nor-BPAPs bearing a 6/5/5 system based on a hexacyclic-fused 1,6-dioxaspiro[4.4]nonane core, and norhyperpalums F and G (8 and 9) exhibit an unusual 6-oxabicyclo[3.2.1]octane architecture. More significantly, compound 2 displayed pronounced cytotoxicities against hepatoma cell lines by the induction of S-phase cell cycle arrest and promotion of cell apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Descoberta de Drogas , Hypericum/química , Floroglucinol/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Floroglucinol/química , Floroglucinol/isolamento & purificação , Relação Estrutura-Atividade
17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(11): 1370-1373, 2019 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-31650750

RESUMO

OBJECTIVE: To review the development and clinical application of ankle prosthesis. METHODS: The recent literature on ankle prosthesis design and clinical application was reviewed and analyzed. RESULTS: Compared with the hip and knee prostheses, the ankle prosthesis develops slowly and has been developed to the third generation. The ankle joint has a special structure of multi-axis movement. The design of the first and second generations of prostheses is not conformed to the biomechanics of the ankle. The third generation of prosthesis is more conform to the characteristics of ankle biomechanics, with high postoperative survival rate and satisfactory clinical outcome. CONCLUSION: At present, the survival rate of ankle prosthesis is low, and there is still much room for improvement in biomechanics, materials, and other aspects.


Assuntos
Articulação do Tornozelo , Prótese Articular , Tornozelo , Membros Artificiais , Fenômenos Biomecânicos , Desenho de Prótese , Falha de Prótese
18.
Molecules ; 13(8): 1822-39, 2008 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-18794787

RESUMO

CoMFA, CoMSIA and eigenvalue analysis (EVA) were performed to study the structural features of 61 diverse dibenzodioxepinone and dibenzodioxocinone analogues to probe cholesteryl ester transfer protein (CETP) inhibitory activity. Three methods yielded statistically significant models upon assessment of cross-validation, bootstrapping, and progressive scrambling. This was further validated by an external set of 13 derivatives. Our results demonstrate that three models have a good interpolation as well as extrapolation. The hydrophobic features were confirmed to contribute significantly to inhibitor potencies, while a pre-oriented hydrogen bond provided by the hydroxyl group at the 3-position indicated a good correlation with previous SAR, and a hydrogen bond acceptor may play a crucial role in CETP inhibition. These derived models may help us to gain a deeper understanding of the binding interaction of these lactone-based compounds and aid in the design of new potent compounds against CETP.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Oxepinas/farmacologia , Oxocinas/farmacologia , Relação Quantitativa Estrutura-Atividade , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Oxepinas/química , Oxocinas/química
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