Mosquito-borne RNA viruses, including but not limited to the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV), pose serious threats to global public health. Current countermeasure approaches are frequently plagued by insufficient coverage, susceptibility to drug resistance, and poor sustainability. Wolbachia, a natural symbiont within mosquitoes, has been shown to block the replication and transmission of mosquito-borne RNA viruses. In recent years, increasing attention has focused on the mechanism of its antiviral action, which involves the regulation of host lipid metabolism. Here, we systematically reviewed the mechanisms by which mosquito-borne RNA viruses disrupt normal lipid metabolism in host cells, elucidating how these viruses rely on host lipids to achieve invasion and form replication complexes. Multiple pathways of Wolbachia disrupting lipid metabolism are highlighted, including rearranging the host lipid environment, competing with viruses for key metabolic resources, regulating mitochondrial-lipid droplet interactions, and altering membrane fluidity. The translational medicine and public health applications of Wolbachia strains were explored, holding potential for advancing novel antiviral strategies based on metabolic disruption.

BackgroundAs a prevalent food-borne zoonotic pathogen, Yersinia pseudotuberculosis (Y. pseudotuberculosis) can lead to severe health issues in both animals and humans. At present, therapeutic options are quite limited. This study evaluated the pharmacological properties of ebselen (EbSe) and its potential as a host-directed therapy (HDT) against Y. pseudotuberculosis infection. EbSe has shown efficacy and safety in clinical settings, particularly against Gram-positive bacteria, as evidenced by its pharmacological properties and clinical applications; however, its efficacy against Gram-negative bacteria remains poorly characterized.MethodsTo systematically elucidate the mechanism of Ebse efficacy, an in vivo mouse model of acute gastroenteritis induced by Y. pseudotuberculosis and an in vitro macrophage-bacteria interaction model were established. Monitoring mouse survival rates and bioluminescence imaging analysis revealed Ebse’s ability against Y. pseudotuberculosis infection. Flow cytometry characterized peritoneal macrophage polarization types and in vitro ones. Transcriptome analysis identified differentially expressed mRNAs in macrophages post-Y.pseudotuberculosis infection, validated by real-time quantitative PCR (RT-qPCR). Cell death was assessed using the CCK-8 assay and propidium iodide (PI) staining, supplemented by morphological observation via transmission electron microscopy (TEM). The intracellular bacteria were quantified through Cytation 5 imaging and fluorescent quantification. Cellular reactive oxygen species (ROS) production was measured by flow cytometry, while glutathione (GSH) content was determined using a micro-reduction GSH assay kit. Intracellular thioredoxin reductase 1 (Txnrd1) activity was assessed via the 5,5’-dithiobis(2-nitrobenzoic acid) (DTNB) assay, with protein expression levels detected by Western blot.Results and discussionEbSe improved overall survival and reduced bacterial burden in mice with gastroenteritis. EbSe was found to modulate macrophage polarization, inhibiting apoptosis and excessive inflammation, as detailed in macrophage function and their role in inflammatory responses. Furthermore, EbSe has been shown to protect Raw264.7 cells from Y. pseudotuberculosis-induced death by enhancing antioxidant defenses. This is evidenced by a reduction in intracellular reactive oxygen species levels and an elevation in glutathione concentrations, and increased thioredoxin reductase 1 activity. Collectively, these findings suggest that EbSe enhances the host resistance to Y. pseudotuberculosis infection, likely through immunomodulatory effects rather than direct antibacterial activity against Gram-negative bacteria.

Due to the wide application of silver-containing dressings and silver-coated medical devices in clinical treatment;the extensive use of antibacterial agents and heavy metal agents in feed factories,Escherichia coli has formed the tolerance to silver ions.To systematically understand the known silver ion resistance mechanisms of E.coli,this article reviews the complex regulatory network and various physiological mechanisms of silver ion tolerance in E.coli,including the regulation of outer membrane porins,energy metabolism modulation,the role of efflux systems,motility regulation,and silver ion reduction.E.coli reduces the influx of silver ions by missing or mutating outer membrane porins such as OmpR,OmpC,and OmpF.It adapts to high concentrations of silver ions by altering the expression of ArcA/B and enhances the efflux capacity of silver ions under high-concentration silver stress via the endogenous Cus system and exogenous Sil system.Furthermore,the motility of bacteria is related to silver tolerance.E.coli has the ability to reduce silver ions,thereby alleviating the oxidative stress induced by silver ions.These findings provide a new perspective for understanding the formation and spread of bacterial tolerance and provide directions for the development of next-generation silver-based antimicrobials and therapies.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

Purpose:Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs. Methods:Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model. Results:The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity. Conclusion:The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.

A gravimetric method is adopted to measure the solid-liquid equilibrium of N-1,N-3,N-5-tris(pyridin-4-yl)benzene-1,3,5-tricarboxamide (TPBTC), a hydrogen-bonded organic framework (HOF) monomer in different solvents (methanol, dichloromethane, isopropanol, n-hexane, acetone, ethanol, 2-butanone, n-butanol, acetonitrile, water, ethyl acetate, and n-propanol). The experiment is carried out at atmospheric pressure, and the experimental temperatures range from 283.15 to 323.15 K. The powder X-ray diffraction analysis was performed on the equilibrium solid-phase characterization of TPBTC in different solvents, and the solid form of solute in equilibrium with different solvents was a mixture of three kinds of crystalline forms and an amorphous form. In the 12 monosolvents, the solubility increased with absolute temperature, and the following order was obtained: 2-butanone > isopropanol > n-propanol >n-butanol > ethyl acetate > acetonitrile > methanol > ethanol > dichloromethane > n-hexane > acetone > water. In the studied temperature range, the maximum and minimum values were recorded for 2-butanone (0.6753 x 10(-3) mol/mol at 323.15 K) and water (0.004650 x 10(-3) mol/mol at 283.15 K), respectively. The solubility behavior and solvent effects in various solvents were first investigated by the hydrogen bond acceptor tendencies as the main factor then interpreted by solvent polarity, cohesive energy density, and steric effect for some exceptions. In addition, the solid-liquid equilibrium data of TPBTC were correlated with the Yaws model and the Apelblat model. Furthermore, the two thermodynamic models were evaluated using the Akaike Information Criterion and Akaike weights. It can be observed that the Yaws model was more appropriate than the Apelblat model.

Some traditional Chinese medicines (TCMs) possess various redox-regulation properties, but whether the redox regulation contributes to antibacterial mechanisms is not known. Here, ginger juice processed Magnoliae officinalis cortex (GMOC) was found to show strong antibacterial activities against some Gram-positive bacteria, but not Gram-negative bacteria including E. coli, while the redox-related transcription factor oxyR deficient E. coli mutant was sensitive to GMOC. In addition, GMOC and its main ingredients, magnolol and honokiol, exhibited inhibitory effects on the bacterial thioredoxin (Trx) system, a major thiol-dependent disulfide reductase system in bacteria. The effects of magnolol and honokiol on cellular redox homeostasis were further verified by elevation of the intracellular ROS levels. The therapeutic efficacies of GMOC, magnolol and honokiol were further verified in S. aureus-caused mild and acute peritonitis mouse models. Treatments with GMOC, magnolol and honokiol significantly reduced the bacterial load, and effectively protected the mice from S. aureus-caused peritonitis infections. Meanwhile, magnolol and honokiol produced synergistic effects when used in combination with several classic antibiotics. These results strongly suggest that some TCMs may exert their therapeutic effects via targeting the bacterial thiol-dependent redox system.

The solubility data of l-valine were measuredby the staticgravimetric method in 12 pure solvents (water, methanol, acetonitrile,1,4-dioxane, n-propanol, isopropanol, ethanol, acetone,methyl acetate, ethyl acetate, n-butanol, and isobutanol)at 283.15-323.15 K (except for 1,4-dioxane at 288.15-328.15K) and 101.2 kPa. The increasing temperature shows a positive effecton l-valine solubility in all the solvents. In addition,the solubility sequence of l-valine at 298.15 K is water> methanol > ethanol >1,4-dioxane > isobutanol > acetone> n-butanol > ethyl acetate > acetonitrile> methyl acetate> isopropanol > n-propanol. The polymorphismof l-valine was investigated by the powder X-ray diffractiontest,and the patterns show that there is no crystal transformation in theprocess of solubility measurement. The main factors influencing thesolubility behavior include solvent polarity (E (T)(30)), hydrogen bond, cohesive energy density, and Hansensolubility parameters (HSPs). Two mathematical models, i.e., the modifiedApelblat model and the Yaws model, were applied to correlate the measuredsolubility data. The ARDs, RMSDs, AIC, and Akaike weights were calculatedto evaluate the fitting results.

The solid-liquid equilibrium solubility and solventeffectsof N-benzyloxycarbonyl-l-serine in 12 monosolventsystems (water, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, n-pentanol, acetonitrile, 2-butanone, acetone, methyl acetate,and ethyl acetate) were reported in this work. All of the solubilitydata were measured at 283.15-323.15 K (5 K interval) by thestatic gravimetric method at a pressure of 101.2 kPa. Among the 12monosolvents, the solubility increased with the increase of absolutetemperature; the order is acetone > isopropanol > n-propanol > sec-butanol > n-butanol> 2-butanone > isobutanol & AP; n-pentanol> methylacetate > ethyl acetate > acetonitrile > water. The solubilityisthe largest in acetone (0.2055 mol & BULL;mol(-1) at323.15 K) and the smallest in water (9.737 x 10(-4) mol & BULL;mol(-1) at 283.15 K). According to thesolubility data analysis results, the solubility of N-benzyloxycarbonyl-l-serine is positively correlated withthe polarity of the solvent. However, its solubility could be affectedby other factors, such as propensity for hydrogen bonding acceptorfor isopropanol, structural similarity for acetone, cohesive energydensity for water, acetonitrile, and sec-butanol,which lead to different dissolution behavior. In addition, the Hansensolubility parameters (HSPs) were used to further analyze its solubilitybehavior. The Yaws model and the modified Apelblat model were employedto correlate the experimental solubility, and the fitting resultsof the two models were both well. In addition, through the comparisonof the AIC values and Akaike weights of the two models, the modifiedApelblat model yielded a more satisfactory correlation result. Theresults may provide a theoretical basis for the preparation and applicationof N-benzyloxycarbonyl-l-serine.

Since the advent of penicillin, humans have known about and explored the phenomenon of bacterial inhibition via antibiotics. However, with changes in the global environment and the abuse of antibiotics, resistance mechanisms have been selected in bacteria, presenting huge threats and challenges to the global medical and health system. Thus, the study and development of new antimicrobials is of unprecedented urgency and difficulty. Bacteria surround themselves with a cell wall to maintain cell rigidity and protect against environmental insults. Humans have taken advantage of antibiotics to target the bacterial cell wall, yielding some of the most widely used antibiotics to date. The cell wall is essential for bacterial growth and virulence but is absent from humans, remaining a high-priority target for antibiotic screening throughout the antibiotic era. Here, we review the extensively studied targets, i.e., MurA, MurB, MurC, MurD, MurE, MurF, Alr, Ddl, MurI, MurG, lipid A, and BamA in the cell wall, starting from the very beginning to the latest developments to elucidate antimicrobial screening. Furthermore, recent advances, including MraY and MsbA in peptidoglycan and lipopolysaccharide, and tagO, LtaS, LspA, Lgt, Lnt, Tol-Pal, MntC, and OspA in teichoic acid and lipoprotein, have also been profoundly discussed. The review further highlights that the application of new methods such as macromolecular labeling, compound libraries construction, and structure-based drug design will inspire researchers to screen ideal antibiotics.

Background In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial.Objective To evaluate the correlation of COX-2 with the prognosis in glioma patients.Methods Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well.Results In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis.Conclusion The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.

Escherichia coli ranks as the number one clinical isolate in the past years in China according to The China Antimicrobial Surveillance Network (CHINET), and its multidrug-resistant (MDR) pathogenic strains account for over 160 million cases of dysentery and one million deaths per year. Here, our work demonstrates that E. coli is highly sensitive to the synergistic combination of SBC3 [1,3-Dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver (I) acetate] and Ebselen, which shows no synergistic toxicity on mammalian cells. The proposed mechanism for the synergistic antibacterial effect of SBC3 in combination with Ebselen is based on directly inhibiting E. coli thioredoxin reductase and rapidly depleting glutathione, resulting in the increase of reactive oxygen species that cause bacterial cell death. Furthermore, the bactericidal efficacy of SBC3 in combination with Ebselen has been confirmed in mild and acute peritonitis mice. In addition, the five most difficult to treat Gram-negative bacteria (including E. coli, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) are also highly sensitive to a synergistic combination of SBC3 and Ebselen. Thus, SBC3 in combination with Ebselen has potential as a treatment for clinically important Gram-negative bacterial infections.

[目的]探讨紫草素(shikonin,SKN)协同依布硒啉(ebselen,EbSe)抗金黄色葡萄球菌(Staphylococcus aureus,S.aureus)的作用及机制.[方法]分光光度法测定紫草素-依布硒啉抗金黄色葡萄球菌活性;碘化丙啶(propidium iodide,PI)染色检测紫草素-依布硒啉杀菌效果;透射电子显微镜观察紫草素-依布硒啉对金黄色葡萄球菌细胞形态的影响.通过荧光探针二氯荧光素二乙酸酯(2',7'-dichlorodihydrofluorescein diacetate,H2DCFDA)检测紫草素-依布硒啉上调细菌胞内活性氧(reactive oxygen species,ROS)产量的能力;利用5,5'-二硫代双(2-硝基苯甲酸)[5,5'-dithiobis-(2-nitrobenzoic acid),DTNB]实验检测紫草素-依布硒啉对硫氧还蛋白还原酶(thioredoxin reductase,TrxR)活性的影响.通过加入还原剂二硫苏糖醇(DL-dithiothreitol,DTT)清除ROS进行挽救实验,复测相关指标,对上述结果进行验证.收集临床多重耐药金黄色葡萄球菌(multidrug-resistant Staphylococcus aureus,MDRS),通过分光光度法测定紫草素-依布硒啉对MDRS的抑菌活性.[结果]依布硒啉与紫草素均对金黄色葡萄球菌有抗菌活性,且10μmol/L依布硒啉与5μmol/L紫草素可发挥显著的协同抑菌活性(P＜0.000 1).紫草素-依布硒啉可协同抑制TrxR活性(P＜0.01),同时显著上调金黄色葡萄球菌胞内ROS产量(P＜0.001).通过回补实验发现,DTT可挽救紫草素-依布硒啉对金黄色葡萄球菌的损伤.紫草素-依布硒啉对MDRS有明显的抑菌活性(P＜0.000 1).[结论]紫草素-依布硒啉可通过协同靶向TrxR,诱导细菌胞内产生大量ROS,介导金黄色葡萄球菌死亡.

Autoimmune diseases a group of disorders elicited by unexpected outcome of lymphocytes self-tolerance failure, and the common members of which include multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, and type 1 diabetes mellitus, etc. The pathogenesis of autoimmune diseases is not fully understood and the current therapeutic regimen's inefficacy in certain cases coupled with low rates of success, exorbitant financial burden, as well as numerous side effects, which do open new avenues for the role of natural products as novel therapeutic agents for auto-inflammatory disorders. Scutellaria baicalensis Georgi is a well-known and widely-recognized herbal medicine with certain ameliorative effect on diverse inflammation-involved dysfunction. Though recent advances do highlight its potential to be applied in the fight against autoimmune diseases, the specific mechanism and the related opinion on the exploring possibility are still limited which hampered the further progress. Here in this timeline review, we traced and collected the evidence of how Scutellaria baicalensis Georgi and its bioactive contents, namely baicalin, baicalein, wogonoside and wogonin affect autoimmune diseases. Moreover, we also discussed the clinical implications and therapeutic potential of Scutellaria baicalensis Georgi and its bioactive contents in autoimmune diseases treatment.

Thioredoxin reductases (TrxRs) belong to the pyridine nucleotide disulfide oxidoreductase family enzymes that reduce thioredoxin (Trx). The couple TrxR and Trx is one of the major antioxidant systems that control the redox homeostasis in cells. The thioredoxin system, comprised of TrxR, Trx and NADPH, exerts its activities via a disulfide-dithiol exchange reaction. Inhibition of TrxR is an important clinical goal in all conditions in which the redox state is perturbed. The present review focuses on the most critical aspects of the cellular functions of TrxRs and their inhibition mechanisms by metal ions or chemicals, through direct targeting of TrxRs or their substrates or protein interactors. To update the involvement of overactivation/dysfunction of TrxRs in various pathological conditions, human diseases associated with TrxRs genes were critically summarized by publicly available genome-wide association study (GWAS) catalogs and literature. The pieces of evidence presented here justify why TrxR is recognized as one of the most critical clinical targets and the growing current interest in developing molecules capable of interfering with the functions of TrxR enzymes.

Abstract Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.

Alongside angiogenesis and lymphangiogenesis, neurogenesis also occurs within the cancer microenvironment. Neurogenesis is a complex process involving multiple factors, among which nerve growth factor (NGF) possesses the dual biological roles of neuron nutrition and axon growth promotion. Thus, NGF might be a key molecule involved in regulating cancer-related neurogenesis, which could play a crucial role in the signal transmission system that controls nerve growth in tumors, and enhances the abilities of migration, invasion and metastasis of tumor cells. The present study aimed to construct differential expression plasmids of NGF, in order to detect whether NGF has a vital role in neurogenesis in breast cancer cells. In the present study, 92 clinical cases of breast cancer were collected and immunohistochemical analysis was performed to verify the existence of neurons in the breast cancer microenvironment. Furthermore, recombinant NGF lentiviral overexpression, knockout and silencing plasmids were constructed, and whether NGF has an effect on neuron growth was preliminarily confirmed, indicating that the successfully constructed plasmids could be used to verify the roles of NGF in cancer-associated neurogenesis.

程序性坏死(Necroptosis)是一种新近发现受调控的细胞坏死,主要依赖于激活后的RIPK1/RIPK3/MLKL等蛋白形成级联复合体并最终导致细胞呈现坏死样特征.越来越多的研究显示,程序性坏死参与了多种炎症性疾病,特别是炎症性肠病的发生发展.对疾病产生机制的研究有助于疾病的预防与治疗,因此该文对程序性坏死及其关键调控蛋白在炎症性肠病中的研究进行了综述,希望通过对现有的实验数据总结能为炎症性肠病的研究以及治疗提供新的思路和方向.

Thioredoxin reductases (TrxRs) belong to the pyridine nucleotide disulfide oxidoreductase family enzymes that reduce thioredoxin (Trx). The couple TrxR and Trx is one of the major antioxidant systems that control the redox homeostasis in cells. The thioredoxin system, comprised of TrxR, Trx and NADPH, exerts its activities via a disulfide-dithiol exchange reaction. Inhibition of TrxR is an important clinical goal in all conditions in which the redox state is perturbed. The present review focuses on the most critical aspects of the cellular functions of TrxRs and their inhibition mechanisms by metal ions or chemicals, through direct targeting of TrxRs or their substrates or protein interactors. To update the involvement of overactivation/dysfunction of TrxRs in various pathological conditions, human diseases associated with TrxRs genes were critically summarized by publicly available genome-wide association study (GWAS) catalogs and literature. The pieces of evidence presented here justify why TrxR is recognized as one of the most critical clinical targets and the growing current interest in developing molecules capable of interfering with the functions of TrxR enzymes.