Dysregulated liver function in SARS-CoV-2 infection:Current understanding and perspectives

Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system,liver enzyme abnormalities exist in around half of the cases,which indicate liver injury,and raise clinical concern.At present,there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response.This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARSCoV-2 infection.

Link between dysregulated hypoxia signaling and aberrant methylation in clear cell renal cell carcinoma？

Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, apoptosis, adhesion, immune evasion, etc. （1）] are considered to be the two central driving pathogenic features in the progression of clear cell Renal Cell Carcinoma （ccRCC） （2,3）.

Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer

Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model

As the body’s internal clock,the circadian rhythm regulates the energy expenditure,appetite,and sleep.There exists a close relationship between the host circadian rhythm and gut microbiota.In this work,a circadian disorder mouse model induced by constant darkness(CD)was constructed to investigate the regulating effects of capsaicin(CAP)on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms.Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue.The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP.Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness,diversity and composition,and restored diurnal oscillations of gut microbes at the phylum and family level.These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice,providing theoretical basis for CAP to be used as a muti-functional ingredient with great healthpromoting effects.

Unveiling the silent link:Normal-tension glaucoma's enigmatic bond with cardiac blood flow

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.

Metabolomic changes in children with autism

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

Dysregulated immunity in PID patients with low GARP expression on Tregs due to mutations in LRRC32

Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses.The identification of the genetic causes of these diseases therefore has critical clinical implications.We performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32,which encodes glycoprotein A repetitions predominant(GARP).These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells(Tregs).Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor function.In a model of conditional Garp deficiency in mice,we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was decreased.Garp deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and stability.Our study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.

The anti-cancerous mechanism of licochalcone A on human hepatoma cell HepG2 based on the miRNA omics

To explore the function of licochalcone A as an anticancer phytochemical on HepG2 cells and investigate its potential mechanisms,we analyzed the microRNAs(miRNAs)expression profile of HepG2 cells in response to licochalcone A(70μmol/L)in vitro.102 dysregulated miRNAs were detected,and SP1 was expected as the transcription factor that regulates the functions of most screened miRNAs.A sum of 431 targets,the overlap of predicted mRNAs from TargetScan,miRDB,and miRtarbase were detected as the targets for these dysregulated miRNAs.FoxO signaling pathway was the hub pathway for the targets.A protein-protein interaction network was structured on the STRING platform to discover the hub genes.Among them,PIK3R1,CDC42,ESR1,SMAD4,SUMO1,KRAS,AGO1,etc.were screened out.Afterwards,the miRNA-target networks were established to screen key dysregulated miRNAs.Two key miRNAs(hsa-miR-133b and hsa-miR-145-5p)were filtered.Finally,the miRNA-target-transcription factor networks were constructed for these key miRNAs.The networks for these key miRNAs included three and two transcription factors,respectively.These identified miRNAs,transcription factors,targets,and regulatory networks may offer hints to understand the molecular mechanism of licochalcone A as a natural anticarcinogen.

Long noncoding RNAs in hepatocellular carcinoma: Novel insights into their mechanism

Hepatocellular carcinoma(HCC) is the predominant subject of liver malignancies which arouse global concern. Advanced studies have found that long noncoding RNAs(lnc RNAs) are differentially expressed in HCC and implicate they may play distinct roles in the pathogenesis and metastasis of HCC. However, the underlying mechanisms remain largely unclear. In this review, we summarized the functions and mechanisms of those known aberrantly expressed lncR NAs identified in human HCC tissues. We hope to enlighten more comprehensive researches on the detailed mechanisms of lncR NAs and their application in clinic, such as being used as diagnostic and prognostic biomarkers and the targets for potential therapy. Although studies on lncR NAs in HCC are still deficient, an improved understanding of the roles played by lncR NAs in HCC will lead to a much more effective utilization of those lnc RNAs as novel candidates in early detection, diagnosis, prevention and treatment of HCC.

Epigenetic dysregulation in Epstein-Barr virus-associated gastric carcinoma: Disease and treatments

Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.

Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature

Herein we report a case of acute liver failure(ALF) and hemophagocytic lymphohistiocytosis(HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient's condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction(PCR) amplifications of varicella-zoster virus(VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient's symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.

Study on gene expression patterns and functional pathways of peripheral blood monocytes reveals potential molecular mechanism of surgical treatment for periodontitis

BACKGROUND Periodontitis is a chronic inflammation of periodontal supporting tissue caused by local factors. Periodontal surgery can change the gene expression of peripheral blood mononuclear cells. However, little is known about the potential mechanism of surgical treatment for periodontitis. AIM To explore the potential molecular mechanism of surgical treatment for periodontitis. METHODS First, based on the expression profiles of genes related to surgical treatment for periodontitis, a set of expression disorder modules related to surgical treatment for periodontitis were obtained by enrichment analysis. Subsequently, based on crosstalk analysis, we proved that there was a significant crosstalk relationship between module 3 and module 5. Finally, based on predictive analysis of multidimensional regulators, we identified a series of regulatory factors, such as endogenous genes, non-coding RNAs (ncRNAs), and transcription factors, which have potential regulatory effects on periodontitis. RESULTS A total of 337 genes related to surgical treatment for periodontitis were obtained, and 3896 genes related to periodontitis were amplified. Eight expression modules of periodontitis were obtained, involving the aggregation of 2672 gene modules. These modules are mainly involved in G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger, and adenylate cyclasemodulating G-protein coupled receptor signaling pathway. In addition, eight endogenous genes (including EGF, RPS27A, and GNB3) were screened by network connectivity analysis. Finally, based on this set of potential dysfunction modules, 94 transcription factors (including NFKB1, SP1, and STAT3) and 1198 ncRNAs (including MALAT1, CRNDE, and ANCR) were revealed. These core regulators are thought to be involved in the potential molecular mechanism of periodontitis after surgical treatment. CONCLUSION Based on the results of this study, we can show biologists and pharmacists a new idea to reveal the potential molecular mechanism of surgical treatment for periodontitis, and provide valuable reference for follow-up treatment programs.

Roles of microRNAs in tumorigenesis and metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is the major subtype of esophageal cancer that is prevalent in Eastern Asia.Despite recent advances in therapy,the outcome of ESCC patients is still dismal.MicroRNAs(miRNAs)are non-coding RNAs which can negatively modulate gene expression at the post-transcriptional level.The involvement and roles of miRNAs have become one of the hot topics of cancer research in recent years.In ESCC,genetic variations within miRNA coding genes were found to have distinct epidemiological significance in different populations.Dysregulated expression of several miRNAs was reported to be associated with therapeutic response.Functionally,miRNAs can act either in an oncogenic or a tumor-suppressive manner during tumorigenesis of ESCC by interrupting signaling pathways associated with cell proliferation,metabolism,cancer stemness,and resistance to chemo-or radiotherapy.Moreover,miRNAs modulate metastasis of ESCC by targeting genes that regulate cytoskeleton dynamics,extracellular matrix remodeling,epithelial-mesenchymal transition,and tumor microenvironment.Most importantly,mounting evidence suggests that inhibiting oncogenic miRNAs or restoring the loss of tumor-suppressive miRNAs has therapeutic potential in the treatment of ESCC.Here,we review and discuss recent studies on the significance,biological functions,and therapeutic potential of miRNAs in tumorigenesis and metastasis of ESCC.

Electromagnetic Waves Collected by a Dental Amalgam Filling Induced Balance Dysregulation and Dizziness over a Period Exceeding 10 Years

This case report describes a woman aged approximately 50 years who has suffered from balance dysregulation and dizziness for more than 10 years. Although the subject underwent several examinations to confirm the etiology of her symptoms, the root cause remained unknown. The symptoms were thought to be caused by electromagnetic wave hypersensitivity because the subject experienced uneasiness and dizziness when a cell phone was held close to her body. A cell phone was used to diagnose the collection of harmful electromagnetic waves, and an amalgam filling was determined to be the cause. The amalgam filling was removed under strict protection, and the subject’s symptoms completely disappeared soon after the filling was removed.

Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions

Precise tuning of gene expression,accomplished by regulato ry networks of transcription factors,epigenetic modifiers,and microRNAs,is crucial for the proper neural development and function of the brain cells.The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis,such as maintaining the cell stemness,cell prolife ration,cell fate decisions,and terminal diffe rentiation into neurons and glial cells.MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression.Together with other gene regulatory factors,microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment.The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain.Deregulated SOX/mic roRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies,including neurodegenerative disorders,traumatic brain injury,and cancer.Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neuro restoration.N umerous studies have confirmed complex intera ctions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma.Keeping in mind the crucial roles of SOX genes and microRNAs in neural development,we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions.Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.

Closer look at white-coat hypertension

This review aims to clarify novel concepts regarding the clinical and laboratory aspects of white-coat hypertension(WCHT). Recent studies on the clinical and biological implications of WCHT were compared with existing knowledge. Studies were included if the WCHT patients were defined according to the 2013 European Society of Hypertension guidelines, i.e., an office blood pressure(BP) of ≥ 140/90 mm Hg, a home BP of ≤ 135/85 mm Hg, and a mean 24-h ambulatory BP of ≤ 130/80 mm Hg. WCHT studies published since 2000 were selected, although a few studies performed before 2000 were used for comparative purposes. True WCHT was defined as normal ABPM and home BP readings, and partial WCHT was defined as an abnormality in one of these two readings. The reported prevalence of WCHT was 15%-45%. The incidence of WCHT tended to be higher in females and in non-smokers. Compared with normotensive(NT) patients, WCHT was associated with a higher left ventricular mass index, higher lipid levels, impaired fasting glucose, and decreased arterial compliance. The circadian rhythm in WCHT patients was more variable than in NT patient's, with a higher pulse pressure and non-dipping characteristics. Compared with sustained hypertension patients, WCHT patients have a better 10-year prognosis; compared with NT patients, WCHT patients have a similar stroke risk, but receivemore frequent drug treatment. There are conflicting results regarding WCHT and markers of endothelial damage, oxidative stress and inflammation, and the data imply that WCHT patients may have a worse prognosis. Nitric oxide levels are lower, and oxidative stress parameters are higher in WCHT patients than in NT patients, whereas the antioxidant capacity is lower in WCHT patients than in NT patients. Clinicians should be aware of the risk factors associated with WCHT and patients should be closely monitored especially to identify target organ damage and metabolic syndrome.

Dysregulation of non-coding RNAs in gastric cancer

Gastric cancer(GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs(nc RNAs), primarily micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of noncoding RNAs, especially mi RNAs and lnc RNAs, in GC. We summarize instances of aberrant expression of the ncR NAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how nc RNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncR NAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncR NAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncR NAs have been identified as targets for the treatment of GC.

Modulating microRNAs in cancer: next-generation therapies

MicroRNAs(miRNAs)are a class of endogenously expressed non-coding regulators of the genome with an ability to mediate a variety of biological and pathological processes.There is growing evidence demonstrating frequent dysregulation of microRNAs in cancer cells,which is associated with tumor initiation,development,migration,invasion,resisting cell death,and drug resistance.Studies have shown that modulation of these small RNAs is a novel and promising therapeutic tool in the treatment of a variety of diseases,especially cancer,due to their broad influence on multiple cellular processes.However,suboptimal delivery of the appropriate miRNA to the cancer sites,quick degradation by nucleases in the blood circulation,and off target effects have limited their research and clinical applications.Therefore,there is a pressing need to improve the therapeutic efficacy of miRNA modulators,while at the same time reducing their toxicities.Several delivery vehicles for miRNA modulators have been shown to be effective in vitro and in vivo.In this review,we will discuss the role and importance of miRNAs in cancer and provide perspectives on currently available carriers for miRNA modulation.We will also summarize the challenges and prospects for the clinical translation of miRNAbased therapeutic strategies.

T helper cell dysregulation with hepatitis B and rebalance with glucocorticoids

AIM: To investigate T helper 17/regulatory T cell alterations in early severe hepatitis B and the effect of glucocorticoids.

Associations of physical activity, sedentary time, and physical fitness with mental health during pregnancy: The GESTAFIT project

Purpose:This study was aimed to analyze the associations of objectively measured physical activity(PA),sedentary time,and physical fitness with mental health in the early second trimester(16§2 gestational weeks)of pregnancy.Methods:From 229 women initially contacted,124 pregnant women participated in the present cross-sectional study.Data were collected between November 2015 and March 2017.The participants wore Actigraph GT3X+Triaxial accelerometers for 9 consecutive days to objectively measure their PA levels and sedentary time.A performance-based test battery was used to measure physical fitness.Self-report questionnaires assessed psychological ill-being(i.e.,negative affect,anxiety,and depression),and psychological well-being(i.e.,emotional intelligence,resilience,and positive affect).Linear regression analyses were adjusted for age,educational level,accelerometer wear time,miscarriages,and low back pain.Results:Moderate-to-vigorous PA was negatively associated with depression(b=0.222,adjusted R2=0.050,p=0.041).Higher levels of sedentary time were negatively associated with positive affect(b=0.260,adjusted R2=0.085,p=0.017).Greater upper-body flexibility was positively associated with better emotional regulation(b=0.195,adjusted R2=0.030,p=0.047).The remaining associations were not significant(all p>0.05).Conclusion:An active lifestyle characterized by higher levels of moderate-to-vigorous PA and lower levels of sedentary time during pregnancy might modestly improve the mental health of pregnant women.Although previous research has focused on the benefits of cardiorespiratory exercise,the present study shows that only upper-body flexibility is related to emotional regulation in early pregnant women.If the present findings are corroborated in further experimental research,physical exercise programs should focus on enhancing flexibility to promote improvements in emotional regulation during early second-trimester of pregnancy.