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1.
Biomater Sci ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899957

RESUMO

Non-healing diabetic wounds often culminate in amputation and mortality. The main pathophysiological features in diabetic wounds involve the accumulation of M1-type macrophages and excessive oxidative stress. In this study, we engineered a nano-enzyme functionalized hydrogel by incorporating a magnesium ion-doped molybdenum-based polymetallic oxide (Mg-POM), a novel bioactive nano-enzyme, into a GelMA hydrogel, to obtain the GelMA@Mg-POM system to enhance diabetic wound healing. GelMA@Mg-POM was crosslinked using UV light, yielding a hydrogel with a uniformly porous three-dimensional mesh structure. In vitro experiments showed that GelMA@Mg-POM extraction significantly enhanced human umbilical vein endothelial cell (HUVEC) migration, scavenged ROS, improved the inflammatory microenvironment, induced macrophage reprogramming towards M2, and promoted HUVEC regeneration of CD31 and fibroblast regeneration of type I collagen. In in vivo experiments, diabetic rat wounds treated with GelMA@Mg-POM displayed enhanced granulation tissue genesis and collagen production, as evidenced by HE and Masson staining. Immunohistochemistry demonstrated the ability of GelMA@Mg-POM to mitigate macrophage-associated inflammatory responses and promote angiogenesis. Overall, these findings suggest that GelMA@Mg-POM holds significant promise as a biomaterial for treating diabetic wounds.

2.
Acta Pharmacol Sin ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719954

RESUMO

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

3.
Phytomedicine ; 127: 155463, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452694

RESUMO

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.


Assuntos
Doença de Alzheimer , Ferroptose , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Caenorhabditis elegans , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Ferro/metabolismo
4.
Angew Chem Int Ed Engl ; 63(22): e202403401, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38527960

RESUMO

Upgrading CO2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis.

5.
Sci Rep ; 14(1): 4748, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413701

RESUMO

Cardiac valve calcification (CVC), characterized by the accumulation of calcium in the heart valves, is highly prevalent among patients undergoing dialysis. This meta-analysis aimed to provide an updated summary of recent studies on the prognostic value of CVC in patients undergoing dialysis. We conducted a search of PubMed, Embase, and Web of Science to identify observational studies investigating cardiovascular or all-cause mortality associated with CVC in dialysis patients until March 2023. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated for the meta-analysis, and the strength and significance of the associations between CVC and mortality outcomes in dialysis patients were assessed. From 6218 initially identified studies, we included 10 critical studies with a total of 3376 dialysis patients in a further meta-analysis. Pooled analyses demonstrated a significant association between CVC and an elevated risk of all-cause and cardiovascular mortality in dialysis patients. In our study, we discovered HRs of 1.592 (95% CI 1.410-1.797) for all-cause mortality and 2.444 (95% CI 1.632-3.659) for cardiovascular mortality. Furthermore, subgroup analysis revealed elevated all-cause mortality among patients with mitral valve calcification (HR 1.572; 95% CI 1.200-2.060) compared to those with aortic valve calcification (HR 1.456; 95% CI 1.105-1.917). Similarly, patients undergoing peritoneal dialysis faced a greater risk for all-cause mortality (HR 2.094; 95% CI 1.374-3.191) than those on hemodialysis (HR 1.553; 95% CI 1.369-1.763). This highlights the possibility of CVC being an independent risk factor for dialysis patients, particularly in relation to mitral valve calcification or peritoneal dialysis.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Doenças das Valvas Cardíacas , Diálise Peritoneal , Humanos , Diálise Renal/efeitos adversos , Diálise Peritoneal/efeitos adversos , Doenças das Valvas Cardíacas/etiologia
6.
Mech Ageing Dev ; 218: 111901, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38215997

RESUMO

Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.


Assuntos
Proteínas de Caenorhabditis elegans , Doença de Parkinson , Saponinas , Animais , Caenorhabditis elegans/metabolismo , Longevidade , Mitofagia , Biogênese de Organelas , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Saponinas/farmacologia
7.
J Am Chem Soc ; 146(5): 2919-2927, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38277794

RESUMO

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

9.
Ageing Res Rev ; 91: 102078, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37758006

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1) is a first responder that recognizes DNA damage and facilitates its repair. Neurodegenerative diseases, characterized by progressive neuron loss driven by various risk factors, including DNA damage, have increasingly shed light on the pivotal involvement of PARP1. During the early phases of neurodegenerative diseases, PARP1 experiences controlled activation to swiftly address mild DNA damage, thereby contributing to maintain brain homeostasis. However, in late stages, exacerbated PARP1 activation precipitated by severe DNA damage exacerbates the disease condition. Consequently, inhibition of PARP1 overactivation emerges as a promising therapeutic approach for neurodegenerative diseases. In this review, we comprehensively synthesize and explore the multifaceted role of PARP1 in neurodegenerative diseases, with a particular emphasis on its over-activation in the aggregation of misfolded proteins, dysfunction of the autophagy-lysosome pathway, mitochondrial dysfunction, neuroinflammation, and blood-brain barrier (BBB) injury. Additionally, we encapsulate the therapeutic applications and limitations intrinsic of PARP1 inhibitors, mainly including limited specificity, intricate pathway dynamics, constrained clinical translation, and the heterogeneity of patient cohorts. We also explore and discuss the potential synergistic implementation of these inhibitors alongside other agents targeting DNA damage cascades within neurodegenerative diseases. Simultaneously, we propose several recommendations for the utilization of PARP1 inhibitors within the realm of neurodegenerative disorders, encompassing factors like the disease-specific roles of PARP1, combinatorial therapeutic strategies, and personalized medical interventions. Lastly, the encompassing review presents a forward-looking perspective along with strategic recommendations that could guide future research endeavors in this field.


Assuntos
Doenças Neurodegenerativas , Ribose , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerase-1/metabolismo , Dano ao DNA , Reparo do DNA
10.
Nanoscale Adv ; 5(15): 3985-3993, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37496617

RESUMO

Nanozymes are a class of nanomaterials that can specifically mimic the structures and catalytic activities as well as overcome limitations of natural enzymes and have hence been considered as a competitive alternative to natural enzymes. At present, plenty of nanozymes, especially those with peroxidase (POD)-like catalytic activity, have been extensively explored for biosensing. In this work, we proposed polyoxometalate-based heterojunction GdP5W30O110@WS2 nanoclusters (NCs) to exert intrinsic POD-like catalytic activity even under harsh catalytic conditions. Detailedly, GdP5W30O110@WS2 NCs possessing conducive POD-like catalytic activity can oxidize chromogenic substrates into colored substances in the presence of H2O2. On the strength of the POD-like catalytic activity of GdP5W30O110@WS2 NCs, a reliable analytical platform is then constructed after the optimization of catalytic conditions for the detection of H2O2, glutathione (GSH) and glucose via a simple TMB colorimetric strategy. This work advances the utilization of versatile polyoxometalate-based nanomaterials for biosensing, dramatically broadening the potential applications of other nanozyme-based biosensors.

12.
Plant Dis ; 107(10): 2971-2977, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36916842

RESUMO

To investigate the presence of hop stunt viroid (HSVd) in mulberry (Morus alba) plants in China, HSVd was detected by reverse transcription (RT)-PCR using dsRNAs extracted from symptomatic or asymptomatic mulberry leaf samples collected from a mulberry field located in Zhenjiang, China, as a template and the primer pairs for HSVd detection. The primer pairs were designed based on the conserved sequence of 25 HSVd variants deposited in the GenBank database. Four out of a total of 53 samples were HSVd-positive, confirming that HSVd is present in mulberry plants in China. The consensus full-length nucleotide (nt) sequence of two HSVd variants determined by sequencing the HSVd variants in these four HSVd-positive samples consisted of 296 nt and shared the highest nt identity of 96.8% with that from plum in Turkey but relatively low identity with those from mulberry in Iran (87.3 to 90.8%). Phylogenetic analysis showed that these HSVd variants clustered together with those of the HSVd-hop group. Analysis of the infectivity and pathogenicity to hosts by the constructed Agrobacterium-mediated dimeric head-to-tail HSVd cDNA infectious clones demonstrated that one of the HSVd variants identified in this study infects the natural host, mulberry plants, and also infects experimental plants, cucumber, and tomato. It probably induces stunting symptoms in HSVd-infected tomatoes but does not induce symptoms on mulberry leaves or in cucumbers. Although HSVd infecting mulberry has been found in Iran, Italy, and Lebanon, this is the first study to report this viroid in naturally infected mulberry plants in China.


Assuntos
Cucumis sativus , Morus , Filogenia , Virulência , Plantas
13.
Front Oncol ; 13: 1035645, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776315

RESUMO

Objective: The aim of this study was to evaluate whether a predictive model based on a contrast enhanced ultrasound (CEUS)-based nomogram and clinical features (Clin) could differentiate Her-2-overexpressing breast cancers from other breast cancers. Methods: A total of 152 pathology-proven breast cancers including 55 Her-2-overexpressing cancers and 97 other cancers from two units that underwent preoperative CEUS examination, were included and divided into training (n = 102) and validation cohorts (n = 50). Multivariate regression analysis was utilized to identify independent indicators for developing predictive nomogram models. The area under the receiver operating characteristic (AUC) curve was also calculated to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared. Results: In the training cohort, 7 clinical features (menstruation, larger tumor size, higher CA153 level, BMI, diastolic pressure, heart rate and outer upper quarter (OUQ)) + enlargement in CEUS with P < 0.2 according to the univariate analysis were submitted to the multivariate analysis. By incorporating clinical information and enlargement on the CEUS pattern, independently significant indicators for Her-2-overexpression were used for further predictive modeling as follows: Model I, nomogram model based on clinical features (Clin); Model II, nomogram model combining enlargement (Clin + Enlargement); Model III, nomogram model based on typical clinical features combining enlargement (MC + BMI + diastolic pressure (DP) + outer upper quarter (OUQ) + Enlargement). Model II achieved an AUC value of 0.776 at nomogram cutoff score value of 190, which was higher than that of the other models in the training cohort without significant differences (all P>0.05). In the test cohort, the diagnostic efficiency of predictive model was poor (all AUC<0.6). In addition, the sensitivity and specificity were not significantly different between Models I and II (all P>0.05), in either the training or the test cohort. In addition, Clin exhibited an AUC similar to that of model III (P=0.12). Moreover, model III exhibited a higher sensitivity (70.0%) than the other models with similar AUC and specificity, only in the test cohort. Conclusion: The main finding of the study was that the predictive model based on a CEUS-based nomogram and clinical features could not differentiate Her-2-overexpressing breast cancers from other breast cancers.

14.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614259

RESUMO

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.


Assuntos
Materiais Biocompatíveis , Traumatismos da Medula Espinal , Humanos , Materiais Biocompatíveis/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal , Medicina Regenerativa , Transplante de Células-Tronco , Regeneração Nervosa
15.
J Mater Chem B ; 11(4): 914-924, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36598013

RESUMO

Photocatalytic antimicrobial therapy (PCAT) is considered to be a potential therapeutic treatment for bacterial-infection diseases. However, the antibacterial efficiency is unsatisfactory due to the limited application scope of photocatalysis. In this work, full-spectrum responsive tungsten disulfide quantum dots (WS2 QDs) are prepared for killing bacteria and enabling wound healing through photocatalytic reactive oxygen species (ROS) generation and glutathione (GSH) depletion. On the one hand, these ultrasmall WS2 QDs exhibit an excellent full spectrum (UV-Vis-NIR)-responsive photocatalytic effect by hindering the recombination of electron-hole pairs, thereby achieving the full use of the energy spectrum. Furthermore, the full-spectrum photocatalytic property of the as-prepared WS2 QDs can be effectively strengthened by redox reaction to deplete GSH for accelerated wound healing. In a word, the as-prepared nanoplatform exhibits the ability to act as an admirable antibacterial reagent with full-spectrum catalytic performance for photocatalytic wound healing therapy. Therefore, this work will not only provide an effective full-spectrum photocatalytic reagent for anti-bacteria therapy and wound healing, but also provide a rational idea for the development of other novel antibacterial agents for applications in the biomedical field.


Assuntos
Pontos Quânticos , Luz , Luz Solar , Antibacterianos/farmacologia , Cicatrização
16.
J Radiol Prot ; 43(1)2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36649650

RESUMO

The neutron dose resulting from external irradiation can be evaluated by measuring the counts of characteristicγrays produced by24Na in the human body. The detection geometry with the highest detection efficiency for measuring the whole-body24Na activity has not been studied. In this work, the MCNP code is used to calculate the spatial distribution of24Na in the human body irradiated by neutrons with different energies in different irradiation geometries. The fluence distribution of24Na characteristicγrays on the body surface is calculated. The counts of24Na characteristicγrays induced by monochromatic neutron irradiation are simulated to fit the scenarios of neutron irradiation by a continuous energy spectrum neutron. When the spontaneous neutrons from252Cf with 1Gy dose irradiate the human body, (3.63-4.35) × 1010 24Na atoms are produced. The lower detection limit for the neutron absorption dose is reduced from ∼100 to less than 1 mGy when the radiation detector is placed over the back of the human body close to the liver. The relative error between the measured counts of24Na characteristic γ rays caused by252Cf neutron irradiation and the counts fitted by monochromatic neutron irradiation data is less than 5.7%. The neutron dose received from a continuous energy spectrum neutron can be acquired quickly and accurately by weighted summing of the data for monochromatic neutron irradiations calculated in this paper, which is more convenient and practical than the previous method.


Assuntos
Corpo Humano , Nêutrons , Humanos , Doses de Radiação
17.
Phytomedicine ; 108: 154483, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36260972

RESUMO

BACKGROUND: There are many types of neurological diseases with complex etiologies. At present, most clinical drugs can only relieve symptoms but cannot cure these diseases. Radix Polygalae, a famous traditional Chinese medicine from the root of plants of the genus Polygala, has the traditional effect of treating insomnia, forgetfulness, and palpitation and improving intelligence and other symptoms of neurological diseases. Saponins are important bioactive components of plants of the genus Polygala and exhibit neuroprotective effects. PURPOSE: This review aimed to summarize the traditional use of Polygala species and discuss the latest phytochemical, pharmacological, and toxicological findings, mainly with regard to Polygala saponins in the treatment of neurological disorders. METHODS: Literature was searched and collected using databases, including PubMed, Science Direct, CNKI, and Google Scholar. The search terms used included "Polygala", "saponins", "neurological diseases", "Alzheimer's disease", "toxicity", etc., and combinations of these keywords. A total of 1202 papers were retrieved until August 2022, and we included 135 of these papers on traditional uses, phytochemistry, pharmacology, toxicology and other fields. RESULTS: This literature review mainly reports on the traditional use of the Polygala genus and prescriptions containing Radix Polygalae in neurological diseases. Phytochemical studies have shown that plants of the genus Polygala mainly include saponins, flavonoids, oligosaccharide esters, alkaloids, coumarins, lignans, flavonoids, etc. Among them, saponins are the majority. Modern pharmacological studies have shown that Polygala saponins have neuroprotective effects on a variety of neurological diseases. Its mechanism of action involves autophagic degradation of misfolded proteins, anti-inflammatory, anti-apoptotic, antioxidative stress and so on. Toxicological studies have shown that Polygala saponins trigger gastrointestinal toxicity, and honey processing and glycosyl disruption of Polygala saponins can effectively ameliorate its gastrointestinal side effect. CONCLUSION: Polygala saponins are the major bioactive components in plants of the genus Polygala that exhibit therapeutic potential in various neurological diseases. This review provides directions for the future study of Polygala saponins and references for the clinical use of prescriptions containing Radix Polygalae for the treatment of neurological diseases.


Assuntos
Doenças do Sistema Nervoso , Fármacos Neuroprotetores , Polygala , Saponinas , Humanos , Saponinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Flavonoides , Etnofarmacologia
18.
bioRxiv ; 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38234727

RESUMO

Hepatitis B virus (HBV) infection is largely noncytopathic and requires the establishment of covalently closed circular DNA (cccDNA), which is considered stable in the nuclei of infected cells. Although challenging, approaches to directly target cccDNA molecules or kill infected cells are recommended to eliminate cccDNA. Herein, cccDNA levels were investigated in HBV-infected chimeric mice with humanized livers. HBV-infected cells support robust replication, progressively retain viral products, and head for cytopathic destruction and cccDNA loss. It is difficult for infected cells to retain cccDNA and remain noncytopathic. Replication-driven cccDNA loss is observed at both phases of spread of and persistent infection. The cccDNA replenishment is required to compensate for cccDNA loss. Blocking cccDNA replenishment pathways reduces cccDNA levels by >100-fold. These results prove an unconventional cccDNA elimination strategy that does not directly target cccDNA but aims to transform spontaneous cccDNA loss into progressive cccDNA elimination by blocking cccDNA replenishment.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986792

RESUMO

Esophageal cancer is a common malignant tumor in China. For resectable ones, surgery is still the primary treatment. At present, the extent of lymph node dissection remains controversial. Extended lymphadenectomy makes metastatic lymph nodes more likely to be resected, which contributed to pathological staging and postoperative treatment. However,it may also increase the risk of postoperative complications and affect prognosis. Therefore, it is controversial how to balance the optimal extent/number of dissected lymph nodes for radical resection with the lower risk of severe complications. In addition, whether the lymph node dissection strategy should be modified after neoadjuvant therapy needs to be investigated, especially for patients who have a complete response to neoadjuvant therapy. Herein, we summarize the clinical experience on the extent of lymph node dissection in China and worldwide, aiming to provide guidence for the extent of lymph node dissection in esophageal cancer.


Assuntos
Humanos , Metástase Linfática/patologia , Excisão de Linfonodo , Linfonodos/patologia , Prognóstico , Neoplasias Esofágicas/patologia , Estadiamento de Neoplasias , Esofagectomia
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-990663

RESUMO

Surgery is an important method for the treatment of resectable esophageal cancer. With the continuous development of minimally invasive esophageal technology, video-assisted thoracoscopic esophagectomy (VATE) has demonstrated obvious advantages over conventional open surgery and has been widely accepted. However, there are still some esophageal cancer patients who cannot benefit from VATE. Inflatable video-assisted mediastinoscopic transhiatal esophagectomy(IVMTE) does not require one-lung ventilation, reduces postoperative complications, expands surgical indications, and brings surgical opportunities for patients with impaired lung function and thoracic lesions, which has become a new choice for the treatment of esophageal cancer. However, the limited field of surgical view and the tunneling surgical approach undoubtedly increase the difficulty of surgery, and how to clearly expose the anatomical structures and thoroughly dissect the lymph nodes has always been the key points and difficulties of surgery. The authors review relevant literatures to discuss the clinical progress and limitations of IVMTE.

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