Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.

Bowel function and inflammation: Is motility the other side of the coin?

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel.On the flip side,functions also arise from its role as an interface with the environment.Indeed,the gut houses microorganisms,collectively known as the gut microbiota,which interact with the host,and is the site of complex immune activities.Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut,especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems.This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

Synchronous gastric and colon cancers:Important to consider hereditary syndromes and chronic inflammatory disease associations

In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon cancers.Synchronous or metachronous primary malignancies at different sites of the gastrointestinal tract pose a unique diagnostic and therapeutic challenge.Multidisciplinary services and strategies are required for the management of multiple site primary malignancies,to provide the best oncological outcomes.Although this study highlights the dual cancers in 76 sporadic cases,the authors excluded 55 patients due to combination of factors which includes;incomplete clinical data,genetic syndrome,gastric stump cancers.In addition,the authors did not elaborate if any patients presented with signet ring cell morphology,E-cadherin mutations or presence of inflammatory bowel disease.Genetic and mutational errors and epithelial field defects from chronic inflammatory diseases of the gastrointestinal tract are important when considering synchronous gastric and colonic cancers.We will briefly discuss these in this editorial.

Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation

Several chronic disorders including type 2 diabetes(T2D),obesity,heart disease and cancer are preceded by a state of chronic lowgrade inflammation.Biomarkers for the early assessment of chronic disorders encompass acute phase proteins(APP),cytokines and chemokines,pro-inflammatory enzymes,lipids and oxidative stress mediators.These substances enter saliva through the blood flow and,in some cases。

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation

Chronic inflammation,through a variety of mechanisms,plays a key role in the occurrence and development of digestive system malignant tumors(DSMTs).In this study,we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation.The development and evaluation of cancer prevention strategies is a longstanding process.Cancer prevention,especially in the early stage of life,should be emphasized throughout the whole life course.Issues such as the time interval for colon cancer screening,the development of direct-acting antiviral drugs for liver cancer,and the Helicobacter pylori vaccine all need to be explored in long-term,large-scale experiments in the future.

Establishment and validation of a nomogram for predicting the risk of liver inflammation in chronic HBV infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant inflammation in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical College from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected,and to prevent overfitting of the model,131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization,to collect the clinic information,serological examination,liver elastography and liver histopathology results.The patients were divided into non-significant inflammation and significant inflammation groups in the modeling group.The R 4.1.1 package and the rms package were used to build the column line graph model,while the Bootstrap method was applied to repeat the sampling 1000 times for internal and external validation,and the H-L goodness of fit test and ROC curve were used to assess the calibration and discrimination of the column line graph model respectively.Results:A total of 180 patients with chronic HBV infection were included,and 92 patients(51.1%)had significant inflammation.In the modeling set,67 patients(51.1%)had significant inflammation.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,GGT,PAB,H.A,PⅢP,CⅣ,L.N,IL-6,LSM and HBeAg for non-significant inflammation and significant inflammation showed statistically significant differences(P<0.05).Nomogram were obtained using stepwise regression analysis to establish a predictive model for the risk of significant inflammation following chronic HBV infection.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 0.279 and 2.098,respectively,corresponding to P values of 0.87 and 0.35,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant inflammation after HBV infection for the modelling and validation groups was 0.895[95%CI(0.843-0.948)]and 0.760[95%CI(0.622-0.897)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that PLT,Ln(HBV-DNA),AST,C桇and LSM were more closely associated with the occurrence of significant inflammation after HBV infection,and a visualization of the occurrence of significant inflammation nomogram was established by comprehensive assessment,and the effectiveness was good.

Even low-grade inflammation impacts on small intestinal function

Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of reduced villus height and crypt depth,increased permeability,as well as altered sugar and peptide absorption in the small intestine after induction of inflammation in experimental models,which is supported by some clinical data.Identification of inflammatory factors which may promote the process of gastrointestinal dysfunction as well as clinical research to verify experimental observations of inflammatory modulation of gastrointestinal function are required.Moreover,nutritional strategies to support functional restitution are needed.

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.

Toxic stress,inflammation and symptomatology of chronic complications in diabetes

Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035.The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009.The effects of toxic stress,the culmination of biological and environmental interactions,on the development of diabetes complications is gaining attention.Stress impacts the hypothalamus-pituitaryadrenal axis and contributes to inflammation,a keybiological contributor to the pathogenesis of diabetes and its associated complications.This review provides an overview of common diabetic complications such as neuropathy,cognitive decline,depression,nephropathy and cardiovascular disease.The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes,associated symptomatology and importance of early identification of symptoms of depression,fatigue,exercise intolerance and pain.

Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea（OSA）.We used a well-described OSA rat model induced with simultaneous intermittent hypoxia.Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled.The rats were exposed to intermittent hypoxia 8 hours daily for 5weeks.The changes of cardiac structure and function were examined by ultrasound.The cardiac pathology,apoptosis,and fibrosis were analyzed by H＆E staining,TUNNEL assay,and picosirius staining,respectively.The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot.Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters（LVIDs）,endsystolic volume（ESV）,end-diastolic volume（EDV）,and blood lactate level and marked reduction in ejection fraction and fractional shortening.Chronic intermittent hypoxia increased TUNNEL-positive myocytes,disrupted normal arrangement of cardiac fibers,and increased Sirius stained collagen fibers.The expression levels of hypoxia induced factor（HIF）-l α,NF-κB,IL-6,and matrix metallopeptidase 2（MMP-2） were significantly increased in the heart of rats exposed to chronic intermittent hypoxia.In conclusion,the left ventricular function was adversely affected by chronic intermittent hypoxia,which is associated with increased expression of HIF-lα and NF-κB signaling molecules and development of cardiac inflammation,apoptosis and fibrosis.

A Clinical Study on the Treat ment of Chronic Pelvic Inflammation of Qi-stagnation with Blood Stasis Syndrome by Penyanqing Capsule (盆炎清胶囊)

Objective： To observe the clinical efficacy of Penyanqing Capsule （盆炎清胶囊, PYQC） in treating pelvic inflammation of Qi-stagnation with blood stasis syndrome. Methods： The randomized, single blinded, parallel positive drug controlled method was adopted, with 82 patients assigned into two groups by envelop method. The 42 patients in the treated group received PYQC 3 times a day, 4 capsules each time taken orally; the 40 patients in the control group were given orally Fuyankang tablets （妇炎康片, FYKT） 3 times a day, 6 tablets each time. The therapeutic course for both groups was 2 months, and 2 courses of treatment were given successively to observe the comprehensive effect, changes of symptoms and signs before and after treatment. The effects of PYQC on hemorrheological character in part of the patients and on the pathogenetic chlamydia and mycoplasma were also observed. Results： The total effective rate in the treated group was 83.3%, which was insignificantly different from that in the control group （77.5%, P〉0.05）. However, PYQC could significantly lower the hemorrheologic indexes in patients and showed definite influence on the pathogenetic chlamydia and mycoplasma. Conclusion： PYQC has good therapeutic effect in treating chronic pelvic inflammation of Qi-stagnation with blood stasis syndrome, and showed definite effect on chlamydia and mycoplasma.

Therapeutic potential of exosome-based personalized delivery platform in chronic inflammatory diseases

In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.

Xanthogranulomatous inflammation requiring small bowel anastomosis revision: A case report

BACKGROUND Xanthogranulomatous inflammation(XGI)is an uncommon process involving an accumulation of inflammatory cells,commonly lipid-laden macrophages.XGI has been described to occur throughout the body but only rarely in the lower gastrointestinal tract.We describe a case of XGI contributing to chronic obstructive symptoms in the terminal ileum,in which the patient had an initial diagnostic laparoscopy,continued to have symptoms,then proceeded to have the definitive treatment.To our knowledge,this is the first report of XGI associated with a prior small bowel anastomosis.CASE SUMMARY We report the case of a 42-year-old female who presented with intermittent epigastric pain and subjective fevers.She had undergone a laparoscopic small bowel resection for Meckel’s diverticulum five years prior.Her workup was notable for computed tomography scan demonstrating mild inflammation and surrounding stranding at the level of the prior anastomosis.She underwent a laparotomy,resection of the prior anastomosis and re-anastomosis,with final histopathological examination findings consistent with mural XGI.CONCLUSION XGI can occur at the site of a prior bowel anastomosis and cause chronic obstructive symptoms.

Antioxidant and anti-inflammatory agents in chronic liver diseases:Molecular mechanisms and therapy

Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral infection,and autoimmune hepatitis,which can lead to liver fibrosis,cirrhosis,and cancer.Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD.Molecular signaling pathways such as AMPactivated protein kinase(AMPK),C-Jun N-terminal kinase,and peroxisome proliferator-activated receptors(PPARs)are implicated in the pathogenesis of CLD.Therefore,antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD,NAFLD,and hepatocellular carcinoma(HCC).In this review,we summarize some powerful products that can be potential applied in all the stages of CLD,from ALD/NAFLD to HCC.The selected agents such asβ-sitosterol,curcumin,genistein,and silymarin can regulate the activation of several important molecules,including AMPK,Farnesoid X receptor,nuclear factor erythroid 2-related factor-2,PPARs,phosphatidylinositol-3-kinase,and lysyl oxidase-like proteins.In addition,clinical trials are undergoing to evaluate their efficacy and safety.

Endothelial injury and inflammation in patients with hyperuricemic nephropathy at chronic kidney disease stages 1-2 and 3-4

BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.

Prostate chronic inflammation type Ⅳ and prostate cancer risk in patients undergoing first biopsy set:Results of a large cohort study

Objective:In prostate specimens,chronic inflammatory infiltrate(CII)type Ⅳ has been detected,but its association with prostate cancer(PCa)is controversial.The aim of the present study is to investigate on associations of CII with PCa detection in patients undergoing prostate first biopsy set.Methods:Ultrasound transrectal-guided biopsies by the transperineal approach were retrospectively evaluated in 441 consecutive patients.The study excluded patients who were in active surveillance,prostate specific antigen(PSA)
30 ng/mL,re-biopsies,incidental PCa after transurethral resection of the prostate(TURP),less than 14 cores or metastatic.Analysis of population and subpopulations(with or without PCa)was performed by statistical methods which included ManneWhitney(U test),KruskaleWallis test,Chi-squared statistic,logistic regression.Multivariate logistic regression models predicting mean probability of PCa detection were established.Results:PCa detection rate was 46.03%.Age,PSA,prostate volume(PV),prostate intraepithelial neoplasia(PIN)and CII were the significant independent predictors of PCa detection.PV(OR Z 0.934)and CII(OR Z 0.192)were both negative independent predictors.CII was a significant negative independent predictor in multivariate logistic regression models predicting the mean probability of PCa detection by age,PSA and PV.The inverse association of CII with PCa does not necessary mean protection because of PSA confounding.Conclusion:In a population of patients undergoing prostate first biopsy set,CII was a strong negative independent predictor of PCa detection.CII type Ⅳ should be considered as an adjunctive parameter in re-biopsy or active surveillance protocols.

Novel Approach to Microbiological Study of Chronic Inflammations at Upper Respiratory Tract: Research of Blood L-Form Microbiota

Background: The recognition of human blood microbiota, consisting of cell wall-deficient microbes (L-forms), is a major challenge today in the field of microbiology. There are accumulating data confirming the concept of “internal” blood L-form microbiota and its significance for health and diseases. Finding out whether the blood microbiota can be of diagnostic and prognostic importance for detection and evaluation of chronic infections anywhere in the body is a major objective. In the context of chronically infected upper respiratory tract (URT), the aim of the current study was to understand whether a local infection can be a source for entry of bacteria and fungi in the blood. Methods: Blood samples from six persons with chronic inflammations in URT diagnosed with hypertrophied adenoids, chronic sinusitis, nasal polyps, chronic naso-pharyngitis and one control healthy person were studied. Blood microbiota assessment methodology that be used, included three phases: 1) isolation of L-form cultures from blood-development and propagation;2) cultivation directed to conversion of L-forms into bacterial and fungal cultures;3) isolation of pure classical bacterial and fungal cultures and their identification by MALDI-TOF method. Results: From the patients were isolated L-forms of opportunistic bacteria (Streptococcus mitis, Roseomonas mucosa, Dermacoccus nishinomiyaensis, Enterococcus faecalis, Acinetobacter johnsonii, Pseudomonas putida, Staphylococcus aureus, Pseudomonas luteola, Enterobacter cloacae) and fungi such as Rhodotorula mucilaginosa, Aspergillus niger, Aspergillus fumigatus and Mucorales. Conclusion: The novel innovative methodology for assessment of blood L-form microbiota was successfully applied for detection of microbes responsible for chronic infections at URT.

Atherosclerotic cardiovascular disease in inflammatory bowel disease:The role of chronic inflammation

Inflammatory bowel disease(IBD)causes systemic vascular inflammation.The increased risk of venous as well as arterial thromboembolic phenomena in IBD is well established.More recently,a relationship between IBD and atherosclerotic cardiovascular disease(ASCVD)has been postulated.Systemic inflammatory diseases,such as rheumatoid arthritis and systemic lupus erythematosus,have well characterized cardiac pathologies and treatments that focus on prevention of disease associated ASCVD.The impact of chronic inflammation on ASCVD in IBD remains poorly characterized.This manuscript aims to review and summarize the current literature pertaining to IBD and ASCVD with respect to its pathophysiology and impact of medications in order to encourage further research that can improve understanding and help develop clinical recommendations for prevention and management of ASCVD in patients with IBD.

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Sudden cardiac arrest in a patient with epilepsy induced by chronic inflammation on the cerebral surface

The present study analyzed a patient with epilepsy due to chronic inflammation on the cerebral surface underwent sudden cardiac arrest. Paradoxical brain discharge, which occurred prior to epileptic seizures, induced a sudden cardiac arrest. However, when the focal brain pressure was relieved, cardiac arrest disappeared. A 27-year-old male patient underwent pre-surgical ram monitoring for 160 hours. During monitoring, secondary tonic-clonic seizures occurred five times. A burst of paradoxical brain discharges occurred at 2-19 seconds （mean 8 seconds） prior to epileptic seizures. After 2-3 seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds （average 16 seconds）. The heart rate subsequently returned to a normal rate. Results revealed arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral surface, combined with poor circulation and increased pressure, lntracranial electrodes were placed using surgical methods. Following removal of the arachnoid adhesions and mucus on the local cerebral surface, paradoxical brain discharge and epileptic seizures occurred three times, but sudden cardiac arrest was not recorded during 150-hour monitoring. Post-surgical histological examination indicated meningitis. Experimental findings suggested that paradoxical brain discharge led to cardiac arrest instead of epileptic seizures; the insult was associated with chronic inflammation on the cerebral surface, which subsequently led to hypertension and poor blood circulation in focal cerebral areas.