genetics

摘要： Hepatocellular carcinoma(HCC)is the second cause of cancer-related mortality.The diagnosis of HCC depends mainly on-fetoprotein,which is limited in its diagnostic and screening capabilities.There is an urgent need for a biomarker that detects early HCC to give the patients a chance for curative treatment.New targets of therapy could enhance survival and create future alternative curative methods.In silico analysis provides both;discovery of biomarkers,and understanding of the molecular pathways,to pave the way for treatment development.This review discusses the role of in silico analysis in the discovery of biomarkers,molecular pathways,and the role the author has contributed to this area of research.It also discusses future aspirations and current limitations.A literature review was conducted on the topic using various databases(PubMed,Science Direct,and Wiley Online Library),searching in various reviews,and editorials on the topic,with overviewing the author’s own published and unpublished work.This review discussed the steps of the validation process from in silico analysis to in vivo validation,to incorporation into clinical practice guidelines.In addition,reviewing the recent lines of research of bioinformatic studies related to HCC.In conclusion,the genetic,molecular and epigenetic markers discoveries are hot areas for HCC research.Bioinformatics will enhance our ability to accomplish this understanding in the near future.We face certain limitations that we need to overcome.

摘要： The management of patients with liver metastases from colorectal cancer is still debated.Several therapeutic options and treatment strategies are available for an extremely heterogeneous clinical scenario.Adequate prediction of patients’outcomes and of the effectiveness of chemotherapy and loco-regional treatments are crucial to reach a precision medicine approach.This has been an unmet need for a long time,but recent studies have opened new perspectives.New morphological biomarkers have been identified.The dynamic evaluation of the metastases across a time interval,with or without chemotherapy,provided a reliable assessment of the tumor biology.Genetics have been explored and,thanks to their strong association with prognosis,have the potential to drive treatment planning.The liver-tumor interface has been identified as one of the main determinants of tumor progression,and its components,in particular the immune infiltrate,are the focus of major research.Image mining and analyses provided new insights on tumor biology and are expected to have a relevant impact on clinical practice.Artificial intelligence is a further step forward.The present paper depicts the evolution of clinical decision-making for patients affected by colorectal liver metastases,facing modern biomarkers and innovative opportunities that will characterize the evolution of clinical research and practice in the next few years.

摘要： As a result of the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)represents a global medical concern in childhood with a closely related increased cardiometabolic risk.Knowledge on NAFLD pathophysiology has been largely expanded over the last decades.Besides the well-known key NAFLD genes(including the I148M variant of the PNPLA3 gene,the E167K allele of the TM6SF2,the GCKR gene,the MBOAT7-TMC4 rs641738 variant,and the rs72613567:TA variant in the HSD17B13 gene),an intriguing pathogenic role has also been demonstrated for the gut microbiota.More interestingly,evidence has added new factors involved in the“multiple hits”theory.In particular,omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment.In fact,different branches of omics including metabolomics,lipidomics(in particular sphingolipids and ceramides),transcriptomics(including micro RNAs),epigenomics(such as DNA methylation),proteomics,and glycomics represent the most attractive pathogenic elements in NAFLD development,by providing insightful perspectives in this field.In this perspective,we aimed to provide a comprehensive overview of NAFLD pathophysiology in children,from the oldest pathogenic elements(including genetics)to the newest intriguing perspectives(such as omics branches).

摘要： BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control.CASE SUMMARY We describe a patient with MODY3 involving a novel splicing mutation,in whom low-dose gliclazide was sufficient to control clinically significant hyperglycemia.Sanger sequencing identified a splicing HNF1A mutation in 12q24 NM_000545.5 Intron5 c.1108-1G>A.Glycemic control has been maintained without insulin therapy for 28 mo after the diagnosis of diabetes.CONCLUSION This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy.

摘要： Early-onset colorectal cancer(EOCRC)has seen an alarming rise worldwide over the past two decades.The reason for this global trend is poorly understood.EOCRC appears to have its own unique clinical and molecular features when compared with late-onset colorectal cancer.Younger patients appear to have more distal or rectal disease,a more advanced stage of disease at presentation,and more unfavorable histological features.Identifying risk factors for EOCRC is the first step in mitigating the rising burden of this disease.Here we summarize several noteworthy biological factors and environmental exposures that are postulated to be responsible culprits.This can hopefully translate in clinical practice to the development of better risk stratification tool for identifying highrisk individuals for early colorectal cancer screening,and identifying areas needed for further research to curb this rising trend.

摘要： BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence.This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media.However,in recent years,the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease(CD)from obscurity to global prominence.These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD.Different scientific societies,mainly from Europe and America,have proposed guidelines based on CD's most recent evidence.AIM To identify the most recent scientific guidelines on CD,aiming to find and critically analyse the main differences.METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language.PubMed was lastly accessed on 1 March 2021.RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions.Differences were noted in the possibility of a no-biopsy diagnosis,HLA testing,follow-up protocols,and procedures.CONCLUSION We found a relatively high concordance between the guidelines for CD.Important modifications have occurred in the last years,especially about the possibility of a no-biopsy diagnosis in children.Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.

摘要： Since the pioneering work by Panksepp et al,the neurobiological bases of attachment behavior have been closely linked with opioid neurotransmission.Candidate gene studies of adult individuals have shown that variation in the muopioid receptor gene(OPRM1)influences attachment behavior.Early maternal care and the A/A genotype of the A118G polymorphism interact in modulating levels of fearful attachment.Compared to their counterparts carrying the A/A genotype,individuals expressing the minor 118G allele show lower levels of avoidant attachment and experience more pleasure in social situations.Brain imaging research has strengthened the biological plausibility of candidate gene studies.The avoidance dimension of attachment correlates negatively with muopioid receptor availability in the thalamus and anterior cingulate cortex,as well as the frontal cortex,amygdala,and insula.Overall,findings from human studies combined with those from animal models suggest that research on the genetic bases of attachment should include the endogenous opioid system among the investigated variables.

摘要： High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease(NAFLD).As a result,this condition has recently become one of the leading causes of hepatocellular carcinoma(HCC).Furthermore,the incidence of NAFLD-associated HCC(NAFLD-HCC)is expected to increase in the near future.Advanced liver fibrosis is the most common risk factor for NAFLD-HCC.However,up to 50%of NAFLDHCC cases develop without underlying liver cirrhosis.Epidemiological studies have revealed many other risk factors for this condition;including diabetes,other metabolic traits,obesity,old age,male sex,Hispanic ethnicity,mild alcohol intake,and elevated liver enzymes.Specific gene variants,such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3,transmembrane 6 superfamily member 2,and membrane-bound O-acyl-transferase domaincontaining 7,are also associated with an increased risk of HCC in patients with NAFLD.This clinical and genetic information should be interpreted together for accurate risk prediction.Alpha-fetoprotein(AFP)is the only biomarker currently recommended for HCC screening.However,it is not sufficiently sensitive in addressing this diagnostic challenge.The GALAD score can be calculated based on sex,age,lectin-bound AFP,AFP,and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC.In addition,emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential.However,further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.

摘要： Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

摘要： In this article,we calculate various topological invariants such as symmetric division degree index,redefined Zagreb index,VL index,first and second exponential Zagreb index,first and second multiplicative exponential Zagreb indices,symmetric division degree entropy,redefined Zagreb entropy,VL entropy,first and second exponential Zagreb entropies,multiplicative exponential Zagreb entropy.We take the chemical compound named Proanthocyanidins,which is a very useful polyphenol in human’s diet.They are very beneficial for one’s health.These chemical compounds are extracted from grape seeds.They are tremendously anti-inflammatory.A subdivision formof this compound is presented in this article.The compound named subdivided grape seed Proanthocyanidins is abbreviated as SGSP_(3).This network SGSP_(3),is converted and modeled into its mathematical graphical formation with the support of the latest mathematical tools.We have also developed many closed formulas for the measurement of entropy for the general chemical structure of the subdivided grape seed Proanthocyanidins network.The achieved outcomes can be correlated with the chemical version of SGSP_(3) to get a better understanding of its biological as well as physical features.