Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management

BACKGROUND Type 2 diabetes mellitus(DM)is an independent risk factor for hepatocellular carcinoma(HCC),while insulin is a potent mitogen.Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers.AIM To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control.METHODS We used data acquired from the Taiwan,Chinaese National Health Insurance research database between 2000 and 2017.We identified patients with DM who were prescribed insulin for>3 months.The herb user group was further defined as patients prescribed herbal medication for DM for>3 months per annum during RESULTS We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017.Among these,46849 patients had used a herbal treatment for DM,and 140547 patients were included as the matched control group.The baseline variables were similar between the herb users and nonusers.DM patients with regular herb use had a 12%decreased risk of HCC compared with the control group[adjusted hazard ratio(aHR)=0.88,95%CI=0.80–0.97].The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers.Patients with a herb use of>5 years cumulatively exhibited a protective effect against development of HCC(aHR=0.82,P<0.05).Of patients who developed HCC,herb users exhibited a longer survival time than nonusers(aHR=0.78,P=0.0001).Additionally,we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents.Our analysis indicated that Astragalus propinquus(Huang Qi)plus Salvia miltiorrhiza Bunge(Dan Shen),and Astragalus propinquus(Huang Qi)plus Trichosanthes kirilowii Maxim.(Tian Hua Fen)were the most frequent combination of single herbs.Meanwhile,Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas.CONCLUSION This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12%in DM patients with regular insulin use.

Inhibiting the formation of neutrophil extracellular trapping: a potential mechanism of Chinese medicine in the treatment of ischemic stroke

Ischemic stroke(IS)is the main killer that endangers the health and life of middle-aged and elderly people worldwide.Inflammatory response plays a key regulatory role in the pathogenesis of IS.After cerebral ischemia,leukocytes rapidly accumulate,penetrate blood vessels and infiltrate brain tissue,thereby activating pro-inflammatory factors in the infarct area to exacerbate nerve damage.Neutrophil extracellular traps(NETs)are fibrous mesh structures released by activated neutrophils outside the cell,which can clear pathogens and cell debris,induce inflammatory responses and exacerbate cerebral ischemia-reperfusion(CI/R)injury.Various traditional Chinese medicines and their main components can improve neurological function defects after IS,and inhibit the formation of NETs,which opens up a new direction for the study of traditional Chinese medicines in the prevention and treatment of IS.

Reduced risk of dementia in patients with type 2 diabetes mellitus using Chinese herbal medicine:A nested case-control study

BACKGROUND Dementia is a prevalent condition in type 2 diabetes mellitus(T2DM)patients.While Chinese herbal medicine(CHM)is often employed as complementary therapy for glycemic control,its effect in controlling likelihood of dementia has not yet been fully elucidated.AIM To compare the risk of dementia between T2DM patients with and without CHM treatment.METHODS We undertook a nested case-control study and obtained data on patients 20-70 years of age who received medical care for T2DM between 2001 and 2010 from the National Health Insurance Research database in Taiwan.Cases,defined as those with dementia that occurred at least one year after the diagnosis of T2DM,were randomly matched to controls without dementia from the study cohort at a 1:1 ratio.We applied conditional logistic regression to explore the associations between CHM treatment and dementia.RESULTS A total of 11699 dementia cases were matched to 11699 non-dementia controls.We found that adding CHM to conventional care was related to a lower risk of dementia[adjusted odds ratio(OR)=0.51],and high-intensity CHM treatment was associated with an adjusted OR of 0.22.CONCLUSION This study shows that the cumulative CHM exposure was inversely associated with dementia risk in an exposureresponse manner,implying that CHM treatment may be embraced as a disease management approach for diabetic patients to prevent dementia.

Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully clarified.Recently,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(S.maltophilia)was significantly increased in both the rumen and milk microbiota.Accordingly,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary gland.Therefore,this study investigated the mechanism by which enterogenic S.maltophilia induces mastitis.Results First,S.maltophilia was labelled with superfolder GFP and administered to mice via gavage.The results showed that treatment with S.maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal leakage.Furthermore,tracking of ingested S.maltophilia revealed that S.maltophilia could migrate from the gut to the mammary gland and induce mastitis.Subsequently,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S.maltophilia.Then,using mouse mammary epithelial cells(MMECs),we verified that S.maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusions In conclusion,the results showed that enterogenic S.maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis.Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

Clinical characteristics of acute non-varicose upper gastrointestinal bleeding and the effect of endoscopic hemostasis

BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.

Electroencephalogram findings in 10 patients with post-stroke epilepsy:A retrospective study

BACKGROUND Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular disease.Long-term seizures can seriously affect the prognosis and quality of life of patients.Electroencephalogram(EEG)is the simplest way to diagnose epilepsy,and plays an important role in predicting seizures and guiding medication.AIM To explore the EEG characteristics of patients with post-stroke epilepsy and improve the detection rate of inter-seizure epileptiform discharges.METHODS From January 2017 to June 2020,10 patients with post-stroke epilepsy in our hospital were included.The clinical,imaging,and EEG characteristics were collected.The stroke location,seizure type,and ictal and interictal EEG manifestations of the patients with post-stroke epilepsy were then retrospectively analyzed.RESULTS In all 10 patients,epileptiform waves occurred in the side opposite to the stroke lesion during the interictal stage;these manifested as sharp wave,sharp-wave complex,or spike discharges in the anterior head lead of the side opposite to the lesion.CONCLUSION In EEG,epileptiform waves can occur in the side opposite to the stroke lesion in patients with post-stroke epilepsy.

A nanobody-based blocking enzyme-linked immunosorbent assay for detecting antibodies against pseudorabies virus glycoprotein E

Pseudorabies(PR)is an acute infectious disease of pigs caused by the PR virus(PRV)and results in great economic losses to the pig industry worldwide.PRV glycoprotein E(gE)-based enzyme-linked immunosorbent assay(ELISA)has been used to distinguish gE-deleted vaccine-immunized pigs from wild-type virus-infected pigs to eradicate PR in some countries.Nanobody has the advantages of small size and easy genetic engineering and has been a promising diagnostic reagent.However,there were few reports about developing nanobody-based ELISA for detecting anti-PRV-gE antibodies.In the present study,the recombinant PRV-gE was expressed with a bacterial system and used to immunize the Bactrian camel.Then,two nanobodies against PRV-gE were screened from the immunized camel by phage display technique.Subsequently,two nanobody-HRP fusion proteins were expressed with HEK293T cells.The PRV-gE-Nb36-HRP fusion protein was selected as the probe for developing the blocking ELISA(bELISA)to detect anti-PRV-gE antibodies.Through optimizing the conditions of bELISA,the amount of coated antigen was 200 ng per well,and dilutions of the fusion protein and tested pig sera were separately 1:320 and 1:5.The cut-off value of bELISA was 24.20%,and the sensitivity and specificity were 96.43 and 92.63%,respectively.By detecting 233 clinical pig sera with the developed bELISA and a commercial kit,the results showed that the coincidence rate of two assays was 93.99%.Additionallly,epitope mapping showed that PRV-gE-Nb36 recognized a conserved conformational epitope in different reference PRV strains.Simple,great stability and low-cost nanobody-based bELISA for detecting anti-PRV-gE antibodies were developed.The bELISA could be used for monitoring and eradicating PR.

Understanding the molecular crossroads in acute liver failure:A pathway to new therapies

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Unveiling significant risk factors for intensive care unit-acquired weakness:Advancing preventive care

In this editorial,we discuss an article titled,“Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning,”published in a recent issue of the World Journal of Clinical Cases.Intensive care unit-acquired weakness(ICU-AW)is a debilitating condition that affects critically ill patients,with significant implications for patient outcomes and their quality of life.This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors.Data from a cohort of 1063 adult intensive care unit(ICU)patients were analyzed,with a particular emphasis on variables such as duration of ICU stay,duration of mechanical ventilation,doses of sedatives and vasopressors,and underlying comorbidities.A multilayer perceptron neural network model was developed,which exhibited a remarkable impressive prediction accuracy of 86.2%on the training set and 85.5%on the test set.The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Artificial intelligence for disease diagnostics still has a long way to go

Artificial intelligence(AI)can sometimes resolve difficulties that other advanced technologies and humans cannot.In medical diagnostics,AI has the advantage of processing figure recognition,especially for images with similar characteristics that are difficult to distinguish with the naked eye.However,the mechanisms of this advanced technique should be well-addressed to elucidate clinical issues.In this letter,regarding an original study presented by Takayama et al,we suggest that the authors should effectively illustrate the mechanism and detailed procedure that artificial intelligence techniques processing the acquired images,including the recognition of non-obvious difference between the normal parts and pathological ones,which were impossible to be distinguished by naked eyes,such as the basic constitutional elements of pixels and grayscale,special molecules or even some metal ions which involved into the diseases occurrence.

Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification

BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

Restenosis is a common complication following coronary angioplasty.The traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut dysbiosis.The aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured rats.As indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of vSMCs.It was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in vSMCs.Meanwhile,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured rats.In conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

Present situation of minimally invasive surgical treatment for early gastric cancer

Minimally invasive surgery is a kind of surgical operation,which is performed by using professional surgical instruments and equipment to inactivate,resect,repair or reconstruct the pathological changes,deformities and wounds in human body through micro-trauma or micro-approach,in order to achieve the goal of treatment,its surgical effect is equivalent to the traditional open surgery,while avoiding the morbidity of conventional surgical wounds.In addition,it also has the advantages of less trauma,less blood loss during operation,less psychological burden and quick recovery on patients,and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer patients.Surgical minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer(EGC):endoscopic mucosal resection(EMR),underwater EMR(UEMR),endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR),endoscopic submu-cosal excavation(ESE),submucosal tunnel endoscopic resection,laparoscopic and endoscopic cooperative surgery(LECS);Among them,EMR,EFTR and LECS technologies have a wide range of applications and different modific-ations have been derived from their respective surgical operations,such as band-assisted EMR(BA-EMR),conven-tional EMR(CEMR),over-the-scope clip-assisted EFTR,no-touch EFTR,the inverted LECS,closed LECS,and so on.These new and improved minimally invasive surgeries are more precise,specific and effective in treating different types of EGC.

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

Vanillylacetone attenuates cadmium chloride-induced hippocampal damage and memory loss through upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression

Memory loss and dementia are major public health concerns with a substantial economic burden.Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment.To investigate whether the antioxidant and anti-inflammatory compound vanillyla cetone(zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride(CdCl_(2)) administration in rats,we explo red the potential involvement of the nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway,which is known to modulate oxidative stress and inflammation.Sixty healt hy male Wistar rats were divided into five groups:vehicle-treated(control),vanillylacetone,CdCl_(2),vanillylacetone+ CdCl_(2),vanillylacetone+ CdCl_(2)+ brusatol(a selective pharmacological N rf2inhibitor) groups.Vanillylacetone effectively attenuated CdCl_(2)-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test.Additionally,vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers(interleukin-6,tumor necrosis factor-α,intracellular cell adhesive molecules) and apoptosis biomarkers(Bax and cleaved caspase-3).The control and CdCl_(2)-treated groups treated with va nillylacetone showed reduced generation of reactive oxygen species,decreased malondialdehyde levels,and increased superoxide dismutase and glutathione activities,along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue.All the protective effects of vanillylacetone we re substantially blocked by the co-administration of brusatol(a selective N rf2 inhibitor).Va nillylacetone mitigated hippocampal damage and memory loss induced by CdCl_(2),at least in part, by activating the nuclear transcription factor Nrf2.Additionally,vanillylacetone exerted its potent antioxidant and antiinflammatory actions.