Interleukins in liver disease treatment

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

Economic and Social Impact Assessment of Chronic Diseases Among the Low-Income Population in Southern Punjab,Pakistan

Introduction:Chronic diseases are becoming more prevalent worldwide.The effects of chronic illnesses are disastrous not only for the diagnosed person but also for their entire family.This study explores chronic diseases’social and economic impact on low-income families.The study aims to determine the economic and social implications of various chronic diseases and the loss of income due to these conditions among low-income individuals in Southern Punjab,Pakistan.Methodology:A sample of 424 patients was selected from different areas of Southern Punjab.Data were collected using a questionnaire that included questions about economic status,self-reported health status,social status,management strategies,and health insurance,among other factors.Results:The mean monthly income of the respondents was found to be 57,097.6 Pakistani rupee(PKR),and the mean monthly expenses for treatment were 8,256.1 PKR.The loss of income was calculated at 15%.Additionally,62%of patients spent more than 10%of their monthly income on managing their disease.Approximately 85%of the respondents reported that chronic diseases affected their social life.Furthermore,80%of patients lacked health insurance.Conclusion:Chronic diseases impose significant economic and social burdens on patients and their families in Southern Punjab.To reduce the burden of chronic diseases,the government should enhance healthcare services in this region and provide health insurance to low-income families.

Hospital Discharge Plan in Family Caregivers of Children with Coronary Artery Aneurysm in Kawasaki Disease: A Review

Objective:The study reviews status,main time nodes and hospital discharge services for family caregivers of children with Kawasaki disease complicated by coronary artery aneurysm to provide references for the development of hospital discharge preparation services for medical personnel and patients.Background:CAL of Kawasaki disease is the main cause of acquired heart disease in children,but there is not enough research on the readiness for hospital discharge.Design:Systematic review of observational and interventional studies.

Creutzfeldt-Jakob disease presenting as Korsakoff syndrome caused by E196A mutation in PRNP gene:A case report

BACKGROUND Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations.In humans,prion diseases result from mutations in the prion protein gene(PRNP).Only a limited number of cases involving a specific PRNP mutation at codon 196(E196A)have been reported.The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease(CJD)caused by E196A mutation has not been documented in the existing literature.CASE SUMMARY A 61-year-old Chinese man initially presented with Korsakoff syndrome,followed by rapid-onset dementia,visual hallucinations,akinetic mutism,myoclonus,and hyperthermia.The patient had no significant personal or familial medical history.Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex,while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism.Routine biochemical and microorganism testing of the cerebrospinal fluid(CSF)yielded normal results.Tests for thyroid function,human immunodeficiency virus,syphilis,vitamin B1 and B12 levels,and autoimmune rheumatic disorders were normal.Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results.A test for 14-3-3 protein in the CSF yielded negative results.Whole-genome sequencing revealed a diseasecausing mutation in PRNP.The patient succumbed to the illness 11 months after the initial symptom onset.CONCLUSION Korsakoff syndrome,typically associated with alcohol intoxication,also manifests in CJD patients.Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome.

Familial aggregation in inflammatory bowel disease:Is it genes or environment?

Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.

Similar clinical characteristics of familial and sporadic inflammatory bowel disease in South Korea

AIM: To investigate differences of clinical characteristics and disease courses between familial and sporadic inflammatory bowel disease (IBD) patients.

Ezetimibe Completely Replaced LDL-Apheresis for the Treatment of Familial Hypercholesterolemia and Coronary Artery Disease after CABG—A Case Report

Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.

The role of DJ-1 complexes and catecholamine metabolism： relevance for familial and idiopathic Parkinson＇s disease

Autosomal recessive mutations in the PARK7 gene,which encodes for the protein DJ-1,result in a loss of function and are a cause of familial Parkinson’s disease（PD）,while increased wild-type DJ-1protein levels are associated with some forms of cancer.Several functions of DJ-1 have been described,with the greatest evidence indicating that DJ-1 is a redox-sensitive protein involved in the regulation of oxidative stress and cell survival.

Treatment of Crohn's disease and familial Mediterranean fever by leukopheresis:Single shot for two targets

Coexistence of Crohn's disease(CD) and familial Mediterranean fever(FMF) is a rare condition and knowledge about this clinical situation is limited with a few case reports in the literature. The treatment of both diseases depends on their individual therapies. However, it is very hard to deal with this coexistence when CD is refractory to standard therapies. Ongoing activity of CD triggers the clinical attacks of FMF and the symptoms like abdominal pain interfere with both disease presentations which can cause problems about diagnostic and therapeutic approach. The main therapeutic agent for FMF is colchicine and diarrhea is the most common side effect of this drug. This side effect also causes problems about management of these diseases when both of them are clinically active. Here we report probably the first case in the literature with coexisting CD and FMF who was successfully treated by leukopheresis since he was refractory to conventional therapies for CD.

Polymorphism of Methionine Synthase Gene in Nuclear Families of Congenital Heart Disease

Objective To investigate the relation of methionine synthase (MS) gene variation with congenital heart disease (CHD) phenotype. Methods One hundred and ninety three CHD patients (94 males and 99 females) and their biological parents (nuclear families) in Liaoning Province were selected as the case group, and another 104 normal persons (60 males and 44 females) and their parents without family history of birth defects as the control group. For all subjects the polymorphism of MS gene A2756G locus was examined by PCR-RFLP method. Results In offspring of the control group the frequencies of MS genotype (+/ -) and allele (+) were 10.7% and 5.3%, without existence of homozygote. The MS genotype distribution and allele frequencies of CHD patients and their mothers were not significantly different from the control (P > 0.05). The frequency of allele (+) in case fathers (5.0 %) was apparently lower than that in the control (9.1%, P=0.060), and the odds ratio (OR) was 0.53 (95% CI: 0.25-1.09). There was no difference in parents' genotype combination between the two groups, and in genotype distribution among different types of CHD. Analysis of genetic transmission indicated that mutation allele (+) existed transmission disequilibrium in CHD nuclear families. The percentage of allele (+) transmitted from parents was lower than that allele (-) with OR 0.26 (95% CI: 0.11-0.60). Conclusion MS gene variation in parents is associated with occurrence of CHD in offspring, and mutation allele (+) in parents may be related with the decrease of CHD risk in offspring.

Relationship Between Polymorphism of Cystathionine beta Synthase Gene and Congenital Heart Disease in Chinese Nuclear Families

Objective To study the relationship between polymorphism of cystathionine beta synthase （CBS） gene and development of congenital heart disease （CHD）. Methods One hundred and twenty-seven CHD case-parent triads were recruited from Liaoning Province as patient group, and 129 healthy subjects without family history of birth defect were simultaneously recruited as control group together with their biological parents. For all subjects the polymorphism of CBS gene G919A locus was examined by PCR-ARMS method, Results The frequencies of three genotypes （w/w, w/m, and m/m） in control group were 27.2%, 58,4%, and 14.4%, respectively, with no significant difference in gender. A significant difference in the allele frequency was found between CHD patients and controls, the wild allele frequency was 67,9% in patients and 55.7% in controls CHD parents＇ genotype distribution was significantly different from that in controls. Further comparison of each type of CHD showed that genotype frequencies in several CHD subtypes were significantly different from those in their corresponding controls. The results of TDT analysis showed that no allele transmission disequilibrium existed in CHD nuclear families. Conclusions CBS gene G919A mutation is associated with the development of CHD, and the mutated allele may decrease the risk of CHD.

Evaluation of Attitudes of Family Physicians toward Occupational Health and Occupational Diseases in Türkiye

Background/Aim: This study evaluated family physicians’ attitudes toward occupational health and disease in Türkiye. Materials and Methods: The study is cross-sectional and descriptive in a quantitative research design. The “Attitude Scale for Physicians toward Occupational Health and Occupational Diseases” developed by Kolcu et al. was used in the study (Cronbach’s α 0.94). Our study aimed to sample the entire country using the stratified sample selection based on geographical region. 349 family physicians were included in the study according to sample size (n: 349). Results: The mean age of the participants in the study was 37.77 ± 8.96 (min: 27, max: 65 years). Of the participants, 65.2% were male. Of the physicians, 33.8% were family medicine specialists, and 38.8% had occupational physician certificates. It was determined that the level of attitude of family physicians toward occupational diseases was insufficient. It was also found that awareness increased as age increased, and awareness and attitude levels did not change according to gender. No significant difference was found in the scale total scores and subdimensions of family physicians’ occupational health and occupational disease attitudes according to the regions they worked in Türkiye. Conclusion: It has been concluded that there is no difference in awareness among family physicians in regions where it is much more important to diagnose an occupational disease, especially in industrial regions. The number of family physicians with occupational physician certificates was very insufficient, and a significant number of those who had occupational physician certificates did not practice occupational medicine.

The role of Interleukin-1 family in cardiovascular disease and its research progress

The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation.Moreover,accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases.Therefore,we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases,including atherosclerosis,myocardial infarction and heart failure.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection

Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Sporadic Creutzfeldt-Jakob Disease Presenting with Visual Disturbance—A Case Report in China

Creutzfeldt-Jakob disease (CJD) is a rare but fatal neurodegenerative prion disease. Classic CJD comprises a clinical triad of rapidly progressive dementia, myoclonus, and EEG abnormality. At initial presentation, this classic triad is present only in a minority of cases. Visual impairment is one of the predominant manifestations in the course of CJD, especially in Heidenhain variant phenotype. We reported a case presenting with progressive blurred vision, along with other neurological symptoms, who diagnosed as sporadic CJD with cortical blindness in China.

Rarely fast progressive memory loss diagnosed as Creutzfeldt-Jakob disease:A case report

BACKGROUND Creutzfeldt-Jakob disease(CJD)is a rare degenerative disease of the central nervous system that can be contagious or hereditary and is a rare cause of rapidly progressive dementia.It almost always results in death within 1-2 years from symptom onset.CASE SUMMARY Here,we report the case of a 57-year-old male who initially experienced dizziness followed by a 1-mo fast decline in memory function.He presented to the local hospital and underwent magnetic resonance imaging and cerebrospinal fluid(CSF)examination,with no definitive diagnosis.However,the symptoms of progressive forgetting worsened.In addition,he exhibited progressive involuntary tremor of the limbs.Then,he came to our hospital,and according to the results of CSF examination,electroencephalography(EEG)and magnetic resonance imaging(MRI)tests and clinical manifestations of cerebellar ataxia,dementia,and myoclonus that rapidly progressed,with a short duration of illness,he was finally diagnosed with sporadic CJD(sCJD).CONCLUSION This case report aims to create awareness among physicians to emphasize auxiliary examination,CSF examination,EEG and MRI tests and recognition of cerebellar ataxia,dementia,and myoclonus that rapidly progress to prompt pursuit of an early diagnosis and identification of sCJD and to reduce complications.

Creutzfeldt-Jakob disease presenting with bilateral hearing loss:A case report

BACKGROUND Sporadic Creutzfeldt-Jakob disease(s CJD)is a prion disease characterized as a fatal transmissible neurodegenerative disorder.Dizziness is often the first presenting symptom of s CJD,but hearing loss as an early manifestation is very rare.CASE SUMMARY A 76-year-old man presented with bilateral sudden hearing impairment and dizziness for 10 d.He was taking medications for hypertension and diabetes.He denied any difficulty with activities of daily living or hearing impairment before the onset of symptoms.Pure tone audiometry showed bilateral severe hearing impairment.Brain magnetic resonance imaging(MRI)and laboratory tests were within normal limits.Given his diagnosis of sudden sensory hearing loss,the patient received corticosteroid treatment but it was ineffective.Two weeks later,he complained of aggravated gait impairment,disorientation,and cognitive impairment.Repeat brain MRI showed diffuse cortical high signal intensities on diffusion-weighted imaging.In cerebrospinal fluid analysis,the real-time quaking-induced conversion assay was positive,and 14-3-3 protein was detected in the by western blotting.Considering all the data,we diagnosed probable s CJD,and the patient’s symptoms rapidly progressed into akinetic mutism.CONCLUSION For patients with abrupt bilateral hearing impairment,especially in the elderly,various differential diagnoses,including s CJD,should be considered.

Novel mutation in a Chinese patient with progressive familial intrahepatic cholestasis type 3

Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.

Clinical and Familial Characteristics of Ten Chinese Patients with Fatal Family Insomnia

Objective Fatal familial insomnia （FFI） is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and familial characteristics often Chinese Patients with FFI. Methods We identified ten FFI cases from the surveillance network for Creutafeldt- Jakob disease （CJD） in China.Final diagnosis of FFI cases was made in accordance with the WHO criteria for CJD.The main clinical features and family histories of these ten FFI cases were analyzed. Results The median age of ten cases at onset was 38 years （from 19 to 55）. The foremost symptoms seemed to be various, including sleep disturbances, vision disorder, dizziness and anorexia. Sleep disturbances appeared in all cases and lasted in the whole clinical courses. Progressive sympathetic symptoms, memory loss, movement disturbances, myoclonus and hypertension were also frequently observed. The median duration of the disease was 9.5 months. EEG and MRI did not figure out special abnormality. 14-3-3 protein in CSF was positive in five out of eight tested patients. Clear family histories were identified in 8 patients. Conclusion The data from our study confirm that the Chinese FFI cases have similar clinical characteristics as that of the Caucasian cases. Compared with other genetic CJD associated mutations, the genetic frequencies of D178N in PRNP are apparently high among the Chinese cases.