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Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.
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Diseño de Fármacos , Descubrimiento de Drogas , Estereoisomerismo , Humanos , AnimalesRESUMEN
Azomethine imines, as a prominent class of 1,3-dipolar species, hold great significance and potential in organic and medicinal chemistry. However, the reported synthesis of centrally chiral azomethine imines relies on kinetic resolution, and the construction of axially chiral azomethine imines remains unexplored. Herein, we present the synthesis of axially chiral azomethine imines through copper- or chiral phosphoric acid catalyzed ring-closure reactions of N'-(2-alkynylbenzylidene)hydrazides, showcasing high efficiency, mild conditions, broad substrate scope, and excellent enantioselectivity. Furthermore, the biological evaluation revealed that the synthesized axially chiral azomethine imines effectively protect dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin, offering a promising therapeutic approach for chemotherapy-induced peripheral neuropathy (CIPN). Remarkably, the (S)- and (R)-atropisomers displayed distinct neuroprotective activities, underscoring the significance of axial stereochemistry.
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Compuestos Azo , Iminas , Tiosemicarbazonas , Estereoisomerismo , Compuestos Azo/farmacología , CatálisisRESUMEN
Tendon adhesion is the most common outcome of tendon or tendon-to-bone healing after injury. Our group developed a hydrogel-nanoparticle sustained-release system previously to inhibit cyclooxygenases (COXs) expression and consequently prevent tendon adhesion and achieved satisfactory results. However, effective treatment of multiple tendon adhesions is always a challenge in research on the prevention of tendon adhesion. In the present study, an M2M@PLGA/COX-siRNA delivery system is successfully constructed using the cell membranes of M2 macrophages and poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Targeting properties and therapeutic effects are observed in mice or rat models of flexor digitorum longus (FDL) tendon injury combined with rotator cuff injury. The results showed that the M2M@PLGA/COX-siRNA delivery system has low toxicity and remarkable targeting properties to the injured areas. Treatment with the M2M@PLGA/COX-siRNA delivery system reduced the inflammatory reaction and significantly improved tendon adhesion in both the FDL tendon and rotator cuff tissues. These findings indicate that the M2M@PLGA delivery system can provide an effective biological strategy for preventing multiple tendon adhesions.
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Biomimética , Nanopartículas , Ratas , Ratones , Animales , ARN Interferente Pequeño/genética , Tendones , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & control , Inflamación/patología , MacrófagosRESUMEN
Herein, a series of chiral δ-lactam frameworks have been synthesized and catalyzed by chiral phosphoric acid (CPA) utilizing two kinds of open-chain aza-dienes and azlactones derived from amino acids. This powerful [4 + 2] annulation produces a broad substrate scope with functional group tolerance in yield up to 97% with up to 98:2 er. Moreover, a facile scale-up and straightforward conversion to diversely substituted products verify the synthetic utility of this method featuring good compatibility and high efficiency.
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OBJECTIVES: The aim of this study was to explore the potential association the cytosolic serine hydroxy methyltransferase (SHMT1) rs1979277 polymorphism and the risk of acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Comprehensive search of Web of Science, PubMed, Ovid, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database electronic database, was performed to identify relevant studies published throughout April 30, 2019. The heterogeneity in the study was judged by the I2 and P-values, and then the random ratio or fixed effect was used to calculate the pooled odds ratios (OR) based on the presence or absence of heterogeneity. Sensitivity analysis is used to estimate the impact of individual studies on aggregate estimates. The publication bias of the study was tested using a funnel plot and an Egger regression. RESULTS: Nine studies with a total of 6492 participants (2971 patients; 3521 controls) were included in this meta-analysis. We found that SHMT1 rs1979277 polymorphism was not significantly associated with the risk of ALL in the dominant model: CC versus CT+TT (OR=0.84, 95% confidence interval [CI]: 0.46-1.54, P=0.57), recessive model: CC+CT versus TT (OR=0.81, 95% CI: 0.44-1.49, P=0.50) and allele model: C versus T (OR=0.84, 95% CI: 0.52-1.35, P=0.48). In subgroup analysis by ethnicity, no significant association were found in dominant, recessive and allele models in both Caucasian and Asian populations. CONCLUSION: Our study indicated that the SHMT1 rs1979277 polymorphism was not associated with the risk of susceptibility to ALL.
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Predisposición Genética a la Enfermedad , Glicina Hidroximetiltransferasa/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metiltransferasas , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
How to accelerate tendon healing remains a clinical challenge. In this study, a suture carrying nanoparticle/pEGFP-basic fibroblast growth factor (bFGF) and pEGFP-vascular endothelial growth factor A (VEGFA) complexes was developed to transfer the growth factor genes into injured tendon tissues to promote healing. Polydopamine-modified sutures can uniformly and tightly absorb nanoparticle/plasmid complexes. After tendon tissues were sutured, the nanoparticle/plasmid complexes still existed on the suture surface. Further, we found that the nanoparticle/plasmid complexes delivered into tendon tissues could diffuse from sutures to tendon tissues and effectively transfect genes into tendon cells, significantly increasing the expression of growth factors in tendon tissues. Finally, biomechanical tests showed that nanoparticle/pEGFP-bFGF and pEGFP-VEGFA complex-coated sutures could significantly increase the ultimate strengths of repaired tendons, especially at 4 weeks after operation. Two kinds of nanoparticle/plasmid complex-coated sutures significantly increased flexor tendon healing strength by 3.7 times for Ethilon and 5.8 times for PDS II, respectively, compared with the corresponding unmodified sutures. In the flexor tendon injury model, at 6 weeks after surgery, compared with the control suture, the nanoparticle/plasmid complex-coated sutures can significantly increase the gliding excursions of the tendon and inhibit the formation of adhesion. These results indicate that this nanoparticle/plasmid complex-coated suture is a promising tool for the treatment of injured tendons.
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Materiales Biocompatibles Revestidos , Técnicas de Transferencia de Gen , Nanopartículas , Suturas , Traumatismos de los Tendones/genética , Traumatismos de los Tendones/terapia , Transgenes , Cicatrización de Heridas , Animales , Supervivencia Celular , Materiales Biocompatibles Revestidos/química , Modelos Animales de Enfermedad , Liberación de Fármacos , Expresión Génica , Terapia Genética , Cinética , Nanopartículas/química , Nanopartículas/ultraestructura , Plásmidos/genética , Transgenes/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/genéticaRESUMEN
In ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair has the effect in protecting damaged neurons, but its mechanism has not been clear. In this study, network pharmacology was used to predict the mechanism of Rehmanniae Radix Praeparata-Corni Fructus in the treatment of ischemic stroke sequela. Through database search and literature retrie-val, 40 active ingredients of Rehmanniae Radix Praeparata and Corni Fructus were obtained, and their targets were obtained through STITCH and TCMSP databases. The targets of ischemic stroke sequela were obtained through OMIM,GAD,TTD and DrugBank databases. By screening the intersections of active ingredients targets and stroke treatment targets, 21 potential targets were obtained. The DAVID database was used for GO enrichment analysis and KEGG pathway analysis of potential targets. GO enrichment analysis showed that Rehmanniae Radix Praeparata-Corni Fructus were mainly involved in regulation of blood pressure, negative regulation of extrinsic apoptotic signaling and positive regulation of angiogenesis. KEGG pathway analysis showed that Rehmanniae Radix Praeparata-Corni Fructus could inhibit inflammatory response and apoptosis signaling pathway by regulating HIF-VEGFA signaling pathway in neural stem cell proliferation, TNF signaling pathway and NF-kappaB signaling pathway. Molecular docking technique was used to verify that Rehmanniae Radix Praeparata-Corni Fructus component has a good binding activity with potential targets. The results showed that in ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair could play an important role in recovering neural function, promoting the proliferation of neural stem cells, angiogenesis, preventing neural cells apoptosis and regulating inflammatory factors.
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Isquemia Encefálica , Cornus , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Simulación del Acoplamiento Molecular , TecnologíaRESUMEN
STUDY QUESTION: What is the effect of two guided self-administered interventions on psychological distress in women undergoing IVF or ICSI? SUMMARY ANSWER: A brief mindfulness intervention significantly reduced depression and improved sleep quality, while the gratitude journal intervention showed no significant effect on any outcome variables. WHAT IS KNOWN ALREADY: Mindfulness and gratitude journal interventions have been found to be beneficial in reducing negative affect and improving well-being. However, there are very few mental health professionals who implement such interventions in low- and middle-income countries. Therefore, two guided self-administered interventions for women with infertility were designed to help them cope with their psychological distress. STUDY DESIGN, SIZE, DURATION: A three-armed, randomized controlled trial was designed to evaluate the mindfulness and gratitude journal interventions for women undergoing IVF/ICSI. Between May 2016 and November 2017, at the reproductive center in a public hospital, 234 women were randomly assigned to the brief mindfulness group (BMG, n = 78), gratitude journal group (GJG, n = 78) or control group (CG, n = 78). The inclusion criteria were being a woman undergoing her first cycle of IVF, having at least junior middle school education and having no biological or adopted children. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female infertility patients (n = 346) were approached, and 112 did not meet the inclusion criteria. All three randomized groups completed questionnaires on the day of down-regulation (T1), the day before embryo(s) transfer (T2), and 3 days before the pregnancy test (T3). The BMG completed four sessions and listened to a 20-minute audio daily, including guided mindfulness breathing and body scan. The GJG completed four sessions and wrote three gratitude journals daily. The CG received routine care. A generalized estimating equation was used in an intention-to-treat analysis. The primary outcome was depression. Secondary outcomes were anxiety, sleep quality, infertility-related stress, mindfulness and gratitude. MAIN RESULTS AND THE ROLE OF CHANCE: Participants of the BMG showed decreased depression (mean difference (MD) = -1.69, [-3.01, -0.37], d = 0.44) and improved sleep quality (MD = -1.24, [-1.95, -0.39], d = 0.43) compared to the CG, but the effect was not significant for anxiety, Fertility Problem Inventory totals, mindfulness, gratitude scores or pregnancy rates. The BMG showed a significant reduction in depression and improvement in sleep quality between T1 and T2, a continuous significant reduction between T1 and T3 and no reduction between T2 and T3. There were no significant effects on any of the variables for the GJG. LIMITATIONS, REASONS FOR CAUTION: The inclusion criteria may result in bias because some participants with low education were excluded and only women with infertility were included. A low compliance rate occurred in the gratitude journals group. Moreover, men were not included in this study. Further research should consider including spouses of the target population. WIDER IMPLICATIONS OF THE FINDINGS: The brief mindfulness intervention was beneficial in decreasing depression and improving sleep quality. Implementation of guided self-administered mindfulness could make the psychological counseling service more accessible for patients with infertility in resource-poor settings. The efficiency and feasibility of the gratitude journal intervention needs to be investigated further. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Social Science Foundation (17BSH054). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16008452. TRIAL REGISTRATION DATE: 9 May 2016. DATE OF FIRST PATIENT'S ENROLMENT: 15 May 2016.
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Ansiedad/terapia , Depresión/terapia , Infertilidad Femenina/psicología , Atención Plena , Distrés Psicológico , Adulto , Ansiedad/etiología , Depresión/etiología , Femenino , Humanos , Aceptación de la Atención de Salud , Embarazo , Índice de Embarazo , SueñoRESUMEN
A series of cyclic Arg-rich mitochondria-penetrating peptides were prepared with variation in the macrocycle size and the chirality of Arg residues. A cyclic heptapeptide was demonstrated to be an efficient mitochondria-specific delivery vector for delivering membrane impermeable peptides.
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Membrana Celular/metabolismo , Péptidos de Penetración Celular/metabolismo , Mitocondrias/metabolismo , Membrana Celular/química , Supervivencia Celular , Péptidos de Penetración Celular/química , Ciclización , Células HeLa , Humanos , Mitocondrias/química , Conformación MolecularRESUMEN
OBJECTIVES: Preoperative fasting, water deprivation, and intraoperative fluid loss and redistribution result in hypovolemia in patients undergoing surgery. Some findings have indicated that the superior vena cava (SVC) diameter and variation, as determined by transesophageal echocardiography during surgery, do not reflect central venous pressure effectively. This study aimed to compare and correlate the SVC diameter and variation with the stroke volume variation for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation. METHODS: Thirty-six patients scheduled for elective gastrointestinal surgery under general anesthesia with invasive positive pressure ventilation were included in this study. After anesthesia induction, the stroke volume variation, SVC diameter, mean arterial pressure, central venous pressure, and pulse were recorded, and measurements after fluid challenge were recorded as well. The SVC variation was calculated before and after the fluid challenge. RESULTS: After the fluid challenge, the SVC diameter markedly increased, whereas the SVC variation and stroke volume variation significantly decreased (P < .05). The optimal cutoff value for the SVC variation was 21.1%, and the area under the curve (AUC) from a receiver operating characteristic curve analysis was 0.849. The optimal cutoff value for the minimal SVC diameter was 1.135 cm, and that AUC was 0.929. In addition, the optimal cutoff value for the maximal SVC diameter was 1.480 cm, and the AUC was 0.862. CONCLUSIONS: The minimal SVC diameter may be an effective indicator for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation.
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Procedimientos Quirúrgicos del Sistema Digestivo , Ecocardiografía Transesofágica/métodos , Fluidoterapia/métodos , Respiración con Presión Positiva/métodos , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/fisiopatología , Anciano , Anestesia General , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The activity of ß-lactam antibiotics is compromised by metallo-ß-lactamases (MBLs). Herein, a series of dithiocarbamate derivatives were designed and synthesized. Their antibacterial activities were tested in combination with meropenem (MEM) against several MBL (NDM and IMP type)-producing clinical isolates. Clinical isolates harboring NDM-1 and IMP-4 became susceptible to MEM when it was combined with dithiocarbamate compounds 4a, 4b or 4f synthesized in this work. Compounds 4a and 4b increased the effectiveness of MEM by up to 2560 times against strains. In vitro bactericidal dynamics tests showed that bacteria died within 24â¯h when they were treated with compound 4fâ¯+â¯MEM. Compounds 4a, 4b and 4f were non-hemolytic and exhibited low toxicity toward HeLa cells in vitro. These data show that compounds containing dithiocarbamate functional group may be helpful in the development of MBL inhibitors.
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Antibacterianos/farmacología , Meropenem/farmacología , Tiocarbamatos/farmacología , Inhibidores de beta-Lactamasas/farmacología , Antibacterianos/síntesis química , Antibacterianos/toxicidad , Enterobacteriaceae/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Células HeLa , Hemólisis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Tiocarbamatos/síntesis química , Tiocarbamatos/toxicidad , Zinc/metabolismo , Inhibidores de beta-Lactamasas/síntesis química , Inhibidores de beta-Lactamasas/toxicidad , beta-Lactamasas/metabolismoRESUMEN
OBJECTIVE: To study the effect of Icariin on rat Leydig cells with TGF-ß1-induced injury. METHODS: We determined the optimal concentration of Icariin for protecting primarily cultured Leydig cells against TGF-ß1-induced injury by methyl thiazolyl tetrazolium assay. We detected the effects of Icariin on the secretion of estradiol (E2) and activity of aromatase in the injured Leydig cells by radioimmunoassay and Tritium water release experiment and its effect on the gap junctional intercellular communication (GJIC) between the Leydig cells by fluorescence distribution after photobleaching. RESULTS: Different concentrations of Icariin showed different degrees of protective effect on the TGF-ß1-treated Leydig cells, the effect observed at 20 µg/ml and at its optimum at 160 µg/ml. After treatment of the injured Leydig cells with Icariin at 160 µg/ml, significant improvement was observed in the E2 secretion and aromatase activity (P<0.01) as well as in the GJIC between the Leydig cells (P<0.01). CONCLUSIONS: Icariin can effectively protect rat Leydig cells against TGF-ß1-induced injury, which is largely attributed to its effects of increasing E2 synthesis, enhancing aromatase activity, and improving GJIC between Leydig cells.
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Flavonoides/farmacología , Uniones Comunicantes , Células Intersticiales del Testículo/efectos de los fármacos , Factor de Crecimiento Transformador beta1/efectos adversos , Animales , Aromatasa/metabolismo , Comunicación Celular , Línea Celular , Células Cultivadas , Estradiol/metabolismo , Masculino , Ratas , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Nitric oxide (NO) is crucial for the progression of early diabetic nephropathy (DN). It is important to clarify the mechanism for the production of NO in mesangial cells (MCs). In this study, the amounts/activities of related factors such as reactive oxygen species (ROS), NO, 3 isoforms of nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), GTP cyclohydrolase I (GTPCH I), Jak2, and Stat1 were determined using high-glucose cultured rat MCs. The results showed that the production of BH4 under oxidative stress was strongly stimulated by its rate-limiting enzyme GTP cyclohydrolase, which increased the expression and activity of inducible NOS to facilitate NO synthesis. Furthermore, the relative quantities of activated-Jak2 and activated-Stat1 were increased. Therefore, Jak2/Stat1 pathway mediated BH4 up-regulation can contribute to excessive NO in high-glucose cultured MCs. Our results will be helpful for screening new targets to improve the therapy for early DN.
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Biopterinas/análogos & derivados , Glucosa/toxicidad , Janus Quinasa 2/biosíntesis , Células Mesangiales/metabolismo , Óxido Nítrico/biosíntesis , Factor de Transcripción STAT1/biosíntesis , Animales , Biopterinas/toxicidad , Células Cultivadas , Células Mesangiales/efectos de los fármacos , Ratas , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
OBJECTIVE: To examine the expression of calreticulin (CRT) and the changes of intracellular free calcium and neuronal apoptosis in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage (HIBD), and to investigate the intervention effects of Shenfu injection. METHODS: Seven-day-old rats were randomly assigned to three groups: control, hypoxic-ischemia (HI) and Shenfu-treated. Each group (n=50) was subdivided into 5 groups sacrificed at 3, 6, 12, 24 and 72 hours. Rat models of HIBD were prepared according to the Rice's method. Rats in the control group only underwent the separation of right common carotidartery. Shenfu injection was administered by intraperitoneal injections right after HI insults and then once daily at a dosage of 10 mL/kg for 3 days in the Shenfu-treated group. The expression of CRT in the cerebral cortex was detected by RT-PCR and Western blot. The free calcium concentrations were determined under a fluorescent microscope. The apoptosis rate was measured by the flow cytometry. RESULTS: Compared with the control group, the expression levels of CRT in the HI and the Shenfu-treated groups were obviously up-regulated (P<0.05), and the expression levels of CRT in the Shenfu-treated group were notably higher than those in the HI group (P<0.05) at all time points. The concentrations of intracellular free calcium and the apoptosis rate of neurons in the cerebral cortex in the Shenfu-treated group were significantly reduced compared with those in the HI group (P<0.05), but increased significantly compared with those in the control group at all time points (P<0.05). CONCLUSIONS: Shenfu injection may have neuroprotective effects against HIBD by up-regulation of CRT expression and relief of calcium overload.
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Apoptosis/efectos de los fármacos , Calreticulina/análisis , Corteza Cerebral/metabolismo , Medicamentos Herbarios Chinos/farmacología , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Neuronas/efectos de los fármacos , Animales , Animales Recién Nacidos , Calcio/metabolismo , Corteza Cerebral/patología , Femenino , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Inyecciones , Masculino , Ratas Sprague-DawleyRESUMEN
Lighting accounts for approximately 22 percent of the electricity consumed in buildings in the United States, with 40 percent of that amount consumed by inefficient incandescent lamps. This has generated increased interest in the use of white electroluminescent organic light-emitting devices (WOLEDS) as the next generation solid-state lighting source, owing to their potential for significantly improved efficiency over incandescent sources, combined with low-cost, high-throughput manufacturability. The research and application of the devices have witnessed great progress. WOLEDS have incomparable advantages for its special characteristics. This progress report sketched the principle of WOLEDS and provided some common structures, and further investigation of the mechanism of different structures was made. Meanwhile, the key technologies of WOLEDS were summarized. Finally, the latest research progress of WOLEDS was reviewed.
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Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.
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Here, we present a versatile, silver-catalyzed multi-auto-tandem reaction involving enamines, alkynals, and nucleophiles, utilizing the highly reactive intermediate azafulvenium. This method allows for flexible and switchable regiodivergent reactions through either intermolecular or intramolecular nucleophilic attacks, which can be controlled by adjusting the catalytic conditions. A range of site-specific functionalized or polycyclic fused pyrrole products were efficiently produced with a high level of chemocontrol.
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Tendons are an important part of the musculoskeletal system. Connecting muscles to bones, tendons convert force into movement. Tendon injury can be acute or chronic. Noticeably, tendon healing requires a long time span and includes inflammation, proliferation, and remodeling processes. The mismatch between endogenous and exogenous healing may lead to adhesion causing further negative effects. Management of tendon injuries and complications such as subsequent adhesion formation are still challenges for clinicians. Due to numerous factors, tendon healing is a complex process. This review introduces the role of various biological and mechanical factors and epigenetic regulation processes involved in tendon healing.
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We studied the healing strength and histological changes of digital flexor tendons repaired using Kessler (core suture knots placed over the tendon surface) and modified Kessler (core suture knots placed between two tendon ends) in 31 long toes of chicken. Four weeks after surgery, the healing tendons were measured in a tensile testing machine, and the adhesion formation and histological changes were observed. The strength of the Kessler repairs was significantly greater than that of the modified Kessler repairs with a 35% mean difference. No significant difference was found between the adhesion scores of the tendons repaired with both techniques. In histological sections, the arrangement of collagen fibers in the modified Kessler repair group was more disordered. We conclude that the tendons repaired with the Kessler method are stronger than those with the modified Kessler technique. The knots between tendon ends are detrimental to the early healing strength of digital flexor tendons.
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Pollos , Procedimientos de Cirugía Plástica , Animales , Técnicas de Sutura , Resistencia a la Tracción , Tendones/cirugía , Suturas , Fenómenos BiomecánicosRESUMEN
Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.