Analysis of the Clinical Value of Surgical Treatment and Postoperative Anti-Infection Treatment of Acute Suppurative Appendicitis

Objective: To explore the clinical value of surgical treatment and postoperative anti-infection treatment for acute suppurative appendicitis. Methods: A total of 116 patients with acute suppurative appendicitis were enrolled in this study. The collection period was from December 2021 to December 2023. The patients were randomly grouped into a control group (surgical treatment) and an observation group (surgical treatment and postoperative anti-infection treatment), of 58 patients each. At the end of the treatment, the results of each index of the two groups were compared. Results: The length of hospitalization time, exhaust time, and incidence of complications in the observation group were shorter than those of the control group (P < 0.05). The total effective rate of the observation group was higher than that of the control group (P < 0.05). Conclusion: It is crucial to perform anti-infective treatment promptly after surgical treatment in patients with acute suppurative appendicitis. It can effectively prevent the occurrence of complications and improve the clinical efficacy. Hence, it is worthy of research and promotion.

Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

Isolation and bioactivity screening of soy isoflavones from soybean glycolipids identifies daidzin as a promising anti-inflammatory agent

Background:Soybean has long been utilized in the realm of traditional Chinese medicine.One of its extracts,soybean glycolipids,serves as a vital by-product of soybean oil refining,but its chemical composition and pharmacological potential have yet to be fully elucidated.Methods:In this study,the chemical components were isolated,and the inhibitory effects of these isolates were explored in different zebrafish inflammatory models by survival rate,Histological examination assay and quantitative Real-time PCR assay.The cytotoxicity of daidzin in RAW264.7 cells was evaluated by cell viability assay,and the effect of daidzin on the release of inflammatory cytokines in RAW264.7 cells was detected by enzyme linked immunosorbent assay(ELISA).Western blotting,immunofluorescence assay and alpha7 nicotinic acetylcholine receptors siRNA transfection assay were used to further explore the anti-inflammatory mechanism of daidzin.Results:Four compounds(verticilloside,soya-cerebroside I,soya-cerebroside II and daidzin)were firstly isolated from the soybean glycolipids,among which verticilloside and daidzin inhibited the lipopolysaccharide,CuSO4-and tail cut-stimulated zebrafish inflammation.Noticeably,daidzin exhibited anti-inflammatory activities by increasing the survival rate,alleviating the inflammatory cells infiltration,and down-regulating the expression of pro-inflammatory cytokines and nuclear factor kappa-B,NF-kappa-B inhibitor alpha,and signal transducer and activator of transcription3 in zebrafish.Moreover,daidzin decreased the secretion of IL-6 and TNF-α,inhibited the nuclear translocations of nuclear factor kappa-B p65 and p-signal transducer and activator of transcription3 as well as the NF-kappa-B inhibitor alpha phosphorylation at Ser32 in RAW 264.7 cells.More importantly,it elevated the expression level of alpha7 nicotinic acetylcholine receptors in both zebrafish and RAW 264.7 cells,and the inhibitory effect of daidzin was attenuated after the addition of alpha7 nicotinic acetylcholine receptors siRNA.Conclusion:Our study revealed that daidzin inhibited inflammation by activating the cholinergic anti-inflammatory pathway and further inhibiting the nuclear factor kappa-B and signal transducer and activator of transcription3 signaling.At the same time,it also promotes the recycling of crude soybean glycolipids and supports the potential use of daidzin as a functional food or natural dietary anti-inflammatory agent.

Anti-inflammatory Mechanism of Yao Medicine Laggerae Alatae Herba

[Objectives]To study the anti-inflammatory effect of Laggerae Alatae Herba extract and its mechanism.[Methods]Inflammation models of xylene-induced ear edema in mice,acetic acid-induced increased permeability of abdominal capillaries in mice,and carrageenan-induced paw edema in mice were established;xylene-induced ear swelling model in bilateral adrenalectomized mice was established.The levels of MDA,NO and SOD in inflammatory tissues of paw were measured.[Results]Compared with the model group,the high and medium dose groups of Laggerae Alatae Herba extract had significant inhibitory effect on xylene-induced ear edema in mice,except for the low dose group(P>0.05);Laggerae Alatae Herba extract inhibited the increase of celiac capillary permeability induced by acetic acid and paw edema induced by carrageenan in mice.Compared with the model group,in the mice model with bilateral adrenal glands removed,the high and medium dose groups of Laggerae Alatae Herba extract could significantly inhibit the xylene induced ear swelling of the mice.The high and medium dose groups of Laggerae Alatae Herba extract could significantly decrease the levels of MDA and NO,and significantly increase the level of SOD in the paw tissue.[Conclusions]The Laggerae Alatae Herba extracts have anti-inflammatory activity,and the anti-inflammatory effect of the extracts does not depend on the hypothalamic-pituitary-adrenal axis(HPAA)system.In addition,the anti-inflammatory mechanism of Laggerae Alatae Herba extract is related to the decrease of MDA and NO and the increase of SOD.

Diabetic retinopathy:Role of inflammation and potential therapies for anti-inflammation

Diabetic retinopathy is a leading cause of blindness among working-age adults.Despite many years of research,treatment options for diabetic retinopathy remain limited and with adverse effects.Discovery of new molecular entities with adequate clinical activity for diabetic retinopathy remains one of the key research priorities in ophthalmology.This review is focused on the therapeutic effects of cannabidiol(CBD),a nonpsychoactive native cannabinoid,as an emerging and novel therapeutic modality in ophthalmology based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy-a retinal disease associated with vascular-neuroinflammation.Special emphasis is placed on novel mechanisms which may shed light on the pharmacological activity asso c iated with CBD preclinically.These include a selfdefence system against inflammation and neurodegeneration mediated by inhibition of equilibrat ive nucleoside transporter and activation of adenosine receptor by treatment with CBD.

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes

Infection is one of the major causes of failure of orthopedic implants. Our previous study demonstrated that nanotube modification of the implant surface, together with nanotubes loaded with quaternized chitosan （hydroxypropyltrimethyl ammonium chloride chitosan, HACC）, could effectively inhibit bacterial adherence and biofilm formation in vitro. Therefore, the aim of this study was to further investigate the in vitro cytocompatibility with osteogenic cells and the in vivo anti-infection activity of titanium implants with HACC-loaded nanotubes （NT-H）. The titanium implant （Ti）, nanotubes without polymer loading （NT）, and nanotubes loaded with chitosan （NT-C） were fabricated and served as controls. Firstly, we evaluated the cytocompatibility of these specimens with human bone marrow-derived mesenchymal stem cells in vitro. The observation of cell attachment, proliferation, spreading, and viability in vitro showed that NT-H has improved osteogenic activity compared with Ti and NT-C. A prophylaxis rat model with implantation in the femoral medullary cavity and inoculation with methiciUin-resistant Staphylococcus aureus was established and evaluated by radiographical, microbiological, and histopathological assessments. Our in vivo study demonstrated that NT-H coatings exhibited significant anti-infection capability compared with the Ti and NT-C groups. In conclusion, HACC-loaded nanotubes fabricated on a titanium substrate show good compatibility with osteogenic cells and enhanced anti-infection ability in vivo, providing a good foundation for clinical application to combat orthopedic implant-associated infections.

Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway

Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.

Study on Anti-infection Effect of Polysaccharide from Agaricus blazei Murrill on Mice

In order to study the anti-infection effect of phoshporylated Agaricus blazei polysaccharide on mice, mice were drenched phoshporylated A. blazei polysaccharide for 14 d, and an A. blazei polysaccharide control group and a blank control group were also set. The mice in all the three groups were infected with Escherichia coli on the 15 th day and the 29 th day of the experiment, the body weight of the mice in each group was recorded, as well as the spleen index on the 29 th day of infection and the 36 th day of the experiment, and the anti- E. coli titer in serum was also detected. The results showed that phoshporylated A. blazei polysaccharide could promote and maintain the development of spleen, and improve the immune response of organisms, thereby resisting bacterial infection. Furthermore, phoshporylated A. blazei polysaccharide has better immunoregulation and anti-infection effects than A. blazei polysaccharide, and could play an important role in veterinary clinical treatment and prevention and control of diseases as a immunologic adjuvant or immunopotentiator.

Anti-inflammation and anti-fibrosis actions of resveratrol on experimental pneumoconiosis

OBJECTIVE To investigate the therapeutic effects and related signaling pathways involved in the actions of resveratrol on experimental pneumoconiosis in vivo and in vitro.METHODS The pneumoconiosis animal model was induced by exposing male SD rats to 15mg·m-3 silica aerosol in an inhalation chamber system for 6h·d-1,5d·week-1 for up to 8 weeks.The vehicle or resveratrol(10or 20mg·kg-1)was preventively or remedially administered to the rats during or after the 4-or 8-week silica exposure(SE)period,respectively.After 4-,8-,and up to 14-week treatment,in vivo near-infrared fluorescence imaging analysis and histological analysis were performed to evaluate the pathological changes in rat lung.Inflammatory cytokines level in bronchoalveolar lavage fluid(BALF)was measured by ELISA testing,and the deposition of fibrotic collagen proteins in lung parenchyma was determined by western blotting and immunohistochemistry analysis.Microarray analysis was performed to screen the signaling pathways involved in the actions of resveratrol on pneumoconiosis in vitro models.Anti-inflammation action and signaling of resveratrol was evaluated on silica-stimulated rat alveolar macrophage,which is one of the crucial effector cells for silica-induced inflammatory response;anti-fibrosis action and signaling of resveratrol was evaluated on TGF-β-induced human lung fibroblast,which acts as a promoter in the later fibrotic process of pneumoconiosis.RESULTS Silica aerosol exposure significantly increased macrophage infiltration and matrix metalloproteinases activity in lung tissue concomitant with the increased levels of inflammatory mediators in BALF.Preventive treatment with resveratrol(20mg·kg-1·d-1)reversed all these biochemical indices as well as histopathological alterations induced by silica exposure.Post-SE resveratrol treatment mildly reduced silica-induced inflammatory response in rat lung with no statistical significance.In vitro study revealed that resveratrol could inhibit alveolar macrophage cell death and decrease the levels of IL-1β and TNF-αinduced by silica particle exposure to cultured alveolar macrophages.Resveratrol was further shown to inhibit the nuclear transition of NF-κB and formation of cleaved caspase-1.Encouragingly,resveratrol preventively attenuated the lung fibrosis,evidenced by less fibrotic nodules formation and collagen proteins expression.No significant improvement on lung fibrosis was observed with post-SE resveratrol treatment.Invitrostudy further demonstrated that resveratrol suppressed TGF-β-induced lung fibroblast proliferation and collagen deposition,concomitant with the depressed activity of TGF-β/Smad signaling in lung fibroblast.CONCLUSION Resveratrol shows the anti-inflammation and anti-fibrosis actions on experimental pneumoconiosis in vivo and in vitro models.The depression of NF-κB,NALP3-inflammasome,and TGF-β/Smad signaling pathways may be involved in the anti-inflammation and anti-fibrosis actions of resveratrol,respectively.Resveratrol could be a potential therapeutic agent for the intervention of pneumoconiosis.

Liaoqiao aqueous extract inhibits B16 melanoma growth involving MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation

Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to study the antitumor activity of Lianqiao aqueous extract against melanoma using cancer cell line-based in vitro and mouse allografl tumor in vivo models. Furthermore, we also investigated the underlying molecular mechanisms, par- ticularly the involvement of anti-inflammation and anti-oxidation properties in its antitumor activity. Methods The proliferation of cancer cells was measured by MTT assay. The transplanted B16-F10 melanoma in C57BL/6 mice were established and used for the evaluation of in vivo antitumor effect of LQ. Tumor growth was monitored twice a week. Ki67 and CD31 were used to detect cancer cell proliferation and angiogenesis in tumor, respectively. The anti-oxidative property of LQ was determined by measuring the levels of ROS, MDA and GSH. The anti-inflamma- tory effect of LQ was evaluated by measuring TNF-α and IL-6 using ELISA kits. Other protein expression was deter- mined by Western Blot. Results LQ strongly inhibited the growth of B16-F10 cells in vitro and the tumor growth in vivo. The survival time of tumor-bearing mice was significantly prolonged by LQ. LQ inhibited cancer cell prolif- eration and angiogenesis in tumor as evidenced by decreased expressions of Ki67 and CD31. Levels of ROS, MDA TNF-α and IL-6 decreased, while GSH increased in LQ treatment group, indicating a strong anti-oxidative and an- ti-inflammatory activity of LQ. The expression of antioxidant proteins Nff-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by LQ treatment. Conclusions LQ exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of LQ in- volved the decreased oxidative stress and inflammation in tumor, which is closely related to the heat-clearing and detoxicating properties of LQ.

Anti-infective therapy durations predict psychological stress and laparoscopic surgery quality in pelvic abscess patients

BACKGROUND The degree of psychological stress and the difficulty and efficacy of laparoscopic surgery differ in patients with pelvic abscesses after different durations of antiinfection treatment.AIM To compare and analyse the effects of different durations of anti-infective therapy on patients’preoperative psychological stress level and the clinical efficacy of laparoscopic surgery in patients with pelvic abscesses to offer a reference for the selection of therapy plans.METHODS A total of 100 patients with pelvic abscesses who were admitted to the Department of Gynecology of Suzhou Ninth Hospital affiliated to Soochow University(Suzhou Ninth People's Hospital)from January 2018 to December 2022 were retrospectively enrolled.According to the different durations of antiinfective therapy,they were divided into Group S(50 patients,received antiinfective therapy for 24-48 h)and Group L(50 patients,received anti-infective therapy for 48-96 h).Baseline data,state-trait anxiety score at admission and before surgery,self-rating anxiety scale(SAS)+self-rating depression scale(SDS)score,surgery time,adhesion grading score,intraoperative blood loss,presence or absence of intraoperative intestinal injury,ureteral injury or bladder injury,postoperative body temperature,length of hospital stay,and presence or absence of recurrence within 3 mo after surgery,chronic pelvic pain,incision infection,dysmenorrhea,menstrual disorder or intestinal obstruction were compared between the S group and the L group.RESULTS There was no significant difference in the background data between the S group and the L group(P<0.05).There was no significant difference in the state-trait anxiety score or SAS+SDS score between the S group and the L group on admission(P<0.05).The state-trait anxiety score and SAS+SDS score of the S group were lower than those of Group L after receiving different durations of anti-infective therapy(P<0.05).There was no significant difference in the incidence of intestinal,ureteral or bladder injury between the S group and the L group(P<0.05).The surgery time of Group S was shorter than that of Group L,and the adhesion score and intraoperative blood loss volume were lower than those of Group L(P<0.05).There was no significant difference in the incidence of incision infection,dysmenorrhea,menstrual disorder or intestinal obstruction between the S group and the L group(P<0.05).The postoperative body temperature of Group S was lower than that of Group L(P<0.05),and the hospital stay was shorter than that of Group L(P<0.05).The incidences of recurrence and chronic pelvic pain within 3 mo after surgery were lower than that of Group L(P<0.05).CONCLUSION Twenty-four to forty-eight hours of anti-infective therapy is better than 48-96 h of anti-infective therapy for patients with pelvic abscesses because the degree of psychological stress is lower,which is more conducive to achieving better outcomes after laparoscopic surgery.

Marine natural products with anti-inflammation effects

The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition.During recent decades,the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases.Correspondingly,a myriad of marine bioactive molecules including terpenes,polypeptides,polysaccharides,sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects.And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases.Herein,the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed,to provide a basis for the research and development of anti-inflammatory marine drugs.

Transforming growth factor β1-mediated anti-inflammation slows progression of midbrain dopaminergic neurodegeneration in Parkinson's disease?

Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as muscle rigidity,bradykinesia and tremor.

Anti-inflammatory effects of Solanum procumbens on a low dose complete Freund's adjuvant-induced arthritis rat model

Objective:To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund’s adjuvantinduced arthritis rat models.Methods:We isolated and identified five compounds in the ethanolsoluble Solanum procumbens extract(SP)with anti-inflammatory effects,including ursolic acid,β-sitosterol,hexadecanoic acid,cisvaccenic acid,and vanillic acid.Additionally,we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms,including paw volumes,local temperatures,withdrawal latency,and mechanical withdrawal threshold at the hind paw and white blood cell(WBC)number from complete Freund’s adjuvant-induced arthritis rat models.Results:We have successfully established a complete Freund’s adjuvant-induced arthritis rat model at a low dose(1 mg/mL).SP extract significantly reduced paw volumes(P<0.05),prolonged withdrawal latencies(P<0.05),decreased local temperature,and increased the mechanical withdrawal threshold(P<0.05),but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers.Conclusions:SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis,but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.

Anti-inflammatory and anti-cancer potential of pterostilbene:A review

Pterostilbene is a natural compound that can be found in various food plants such as blueberries,grapes,and peanuts.It has also been reported to be extracted from Pterocarpus indicus,a tree species native to India and Southeast Asia.Pterostilbene exhibits various pharmacological activities such as antioxidants,anti-proliferation,anti-microbial,and anti-inflammatory activities with favorable pharmacokinetic properties,such as high oral bioavailability and longer half-life.The anti-inflammatory effect of pterostilbene has been reported to contribute to its therapeutic effects in many chronic inflammatory diseases.Besides,pterostilbene has anti-cancer activity on various types of cancers due to its ability to induce cell cycle arrest and apoptosis.Hence,in this review,we discuss the anti-inflammatory and anti-cancer activities of pterostilbene in preclinical studies.

Study of the anti-inflammatory effect of the Traditional Mongolian Medicine Hohgardi-9 in acute lung injury

Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism of action are unknown.In this study,we explored the bioactive compounds in Hohgardi-9 and the mechanism underlying its therapeutic effect against acute lung injury(ALI).Methods:We obtained the main components of Hohgardi-9 and analyzed the targets related to ALI by searching the traditional Chinese medicine systems pharmacology database and existing literature.Then,we constructed the compound-target network using Cytoscape 3.8.0 software to obtain the bioactive compounds in Hohgardi-9 against ALI.We used a string database to investigate the interaction between the possible protein targets of Hohgardi-9.We also performed Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict its anti-ALI mechanism.Further,to verify the therapeutical effects of Hohgardi-9,we used an ALI rat model and analyzed the components of Hohgardi-9 found in the rat plasma using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry.Results:The network pharmacology and plasma component analysis showed that Hohgardi-9 contained 31 potentially bioactive components,including quercetin,herbacetin,izoteolin,and columbinetin acetate,which affected the NF-κB,TLR,and TNF signaling pathways via key targets,such as RELA(p65)and TLR4.The in vivo experiments using hematoxylin and eosin staining revealed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats.Simultaneously,Hohgardi-9 significantly reduced the expression levels of genes encoding inflammatory factors,such as TRL4,TNF-α,IL-1β,and ICAM1,in the lungs of ALI rats.Conclusion:Hohgardi-9 alleviated ALI by inhibiting inflammation-related gene expression through its active ingredients,such as quercetin and herbacetin.

Nanozyme‑Engineered Hydrogels for Anti‑Inflammation and Skin Regeneration

Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.

An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis:an evidence-based review

Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunction of the endothelial cells(ECs)and vascular smooth muscle cells(VSMCs),which may eventually lead to the formation of plaques.Xanthophylls,one of the main groups of carotenoids,have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties.However,the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear,and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed.In this regard,we conducted a comprehensive literature search in four scientific databases(Pub Med,Google Scholar,Science Direct and Web of Science)and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects.Based on the evidence from in vitro and in vivo studies,we explored several potential mechanisms,including antioxidant effect,anti-inflammatory effect,regulation of lipid metabolism,and modulation of ECs and VSMCs dysfunction,and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking.In addition,epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls,high plasma/serum xanthophylls and a reduced risk of atherosclerosis.Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse,whilst indirect clinical evidence was only limited to astaxanthin and lutein.Therefore,well-designed long-term randomized controlled trials(RCTs)are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.

Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Resveratrol combats chronic diseases through enhancing mitochondrial quality

Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.