AIM To investigat the influence of hemochromatosis gene(Hfe) mutation on ^(59)Fe labelled duodenal heme absorption in mice.METHODS Heme absorption was measured in Hfe wild type and Hfe^((-/-)) mice by the duodenal tie...AIM To investigat the influence of hemochromatosis gene(Hfe) mutation on ^(59)Fe labelled duodenal heme absorption in mice.METHODS Heme absorption was measured in Hfe wild type and Hfe^((-/-)) mice by the duodenal tied loop and by oral gavage methods. The m RNA expression of heme oxygenase(HO-1), Abcg2 and Flvcr1 genes and levels were determined by quantitative polymerase chain reaction.RESULTS Heme absorption was significantly increased in homozygous Hfe^((-/-)) mice despite significant hepatic and splenic iron overload. While duodenal HO-1 mRNA was highly expressed in the wild type and Hfe^((-/-)) heme-treated group following 24 h heme administration, Flvcr1 a mRNA decreased. However, Abcg2 mRNA expression levels in duodenum remained unchanged. CONCLUSION Heme absorption was enhanced in Hfe^((-/-)) mice from both duodenal tied-loop segments and by oral gavage methods. HO-1 m RNA levels were enhanced in mice duodenum after 24 h of heme feeding and may account for enhanced heme absorption in Hfe^((-/-)) mice. Implications for dietary recommendations on heme intake by Hfe subjects to modulate iron loading are important clinical considerations.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorec...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.展开更多
DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expres...DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.展开更多
A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to ...A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori-associated diseases is determined by an array of ...Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori-associated diseases is determined by an array of virulence factors. Although extensive studies have been conducted globally, data on the distribution of Helicobacter pylori virulence genes in Libya remain limited, constraining insights into the pathogenicity of local strains and hindering the development of targeted interventions. This study aimed to evaluate the prevalence of H. pylori infection, characterize essential virulence genes [vacA variants (s1/s2, m1/m2), cagA, and iceA1], and examine their association with gastroduodenal diseases among Libyan patients. Gastric biopsies from 144 participants were analyzed using polymerase chain reaction (PCR) assays, and risk factor data were collected via questionnaires. H. pylori was detected in 63.2% of samples by PCR. The vacA gene was present in 84.6% of cases, cagA in 58.2%, and iceA1 in 29.7%. Among vacA variants, s1 allele was most common (53.2%), followed by m1 (42.9%), m2 (37.7%), and s2 (13%) alleles. Significant associations were identified between specific virulence genes and the development of gastroduodenal diseases, highlighting their role in pathogenicity. This investigation is one of Libya’s first comprehensive assessments of H. pylori virulence factors, addressing a critical epidemiological gap. The high prevalence of virulence genes suggests their potential as disease biomarkers. These findings contribute to a deeper understanding of H. pylori pathogenicity within the Libyan population and establish a basis for future clinical interventions and public health strategies to manage and prevent H. pylori-associated diseases in Libya and comparable regions.展开更多
BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine recept...BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.展开更多
Asian rice comprises two major subspecies:Xian(X)and Geng(G),and the diverged resistance genes(R)have provided a foundation for breeding improved cultivars to control rice blast disease.After conducting two-phase alle...Asian rice comprises two major subspecies:Xian(X)and Geng(G),and the diverged resistance genes(R)have provided a foundation for breeding improved cultivars to control rice blast disease.After conducting two-phase allele mining using six updated FNP marker systems,the functional haplotypes at Pit,Pib,and Pi63 strictly diverged into the X-populations and were defined as X-R loci,while those at Pi54,Pi37,and Pi36 into the G-populations as G-R loci.The genic diversity at the three X-R loci(16 alleles)was twofold higher than that at the three G-R loci(8 alleles),and the allelic diversity in the Southern region(21 alleles)was nearly double that in the Northeastern region(11 alleles).Both observations reflect a significant difference in genetic diversity between X-and G-populations,and indicate that the effective R-genes mainly originated from X-subspecies.Based on the allelic structures characterized by a set of 10 parameters,8 and 16 alleles were respectively recognized as favorable and promising ones for the regional breeding programs.The genotypic structures of the two regional populations were almost different,indicating that the diverged alleles have been further assembled into two series of regional genotypes through long-term breeding programs,despite the presence of one-third of region-common alleles.The genotypic diversity in the Southern region(55 genotypes)was nearly twice as high as that in the Northeastern region(28),which perfectly reflects the aforementioned differences in both genic and allelic diversities.After analyzing the genotypic structures using a set of 13 parameters,4 and 23 genotypes,respectively,can be recommended as the favorable and promising ones for the regional breeding programs.The case study serves as a concrete sample of how to identify the favorable and promising alleles and genotypes,and beneficial parents based their comprehensive population structures for gene-designed breeding.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat...Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS...BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune responses.As a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in HCC.However,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor cells.AIM To investigate the dual-regulation mechanism of cGAS-STING in HCC.METHODS This review was conducted according to the PRISMA guidelines.The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases.Through rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.RESULTS All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 studies.After removing duplicates,remaining 964 records were screened.Ultimately,55 articles met the inclusion criteria and were included in this review.CONCLUSION Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its progression.Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Mole...Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.展开更多
The color and pattern of watermelon rind are crucial external traits that directly affect consumer preferences.Watermelons with stripes having a stronger color than the background rind are ideal for studying stripe pa...The color and pattern of watermelon rind are crucial external traits that directly affect consumer preferences.Watermelons with stripes having a stronger color than the background rind are ideal for studying stripe patterns in plants,while there is still limited knowledge about the genetic mechanisms underlying stripe coloration due to the lack of germplasm resources.In this study,we focused on a watermelon germplasm with colorless stripes,and genetic analysis revealed that the trait is controlled by a single recessive gene.The gene Clsc(Citrullus lanatus stripe coloration),which is responsible for the colorless stripe,was localized into a 147.6 kb region on Chr9 by linkage analysis in a large F2 mapping population.Further analysis revealed that the Cla97C09G175170 gene encodes the APRR2 transcription factor,plays a crucial role in determining the watermelon colorless stripe phenotype and was deduced to be related to chlorophyll synthesis and chloroplast development.Physiological experiments indicated that Cla97C09G175170 may significantly influence chloroplast development and chlorophyll synthesis in watermelon.The results of this study provide a better understanding of the molecular mechanism of stripe coloration in watermelon and can be useful in the development of marker-assisted selection(MAS)for new watermelon cultivars.展开更多
The use of a stable reference gene is fundamental for achieving reliable quantitative qRT-PCR (qPCR) results. Developing and evaluating the stability of reference genes is necessary for studying the molecular mechanis...The use of a stable reference gene is fundamental for achieving reliable quantitative qRT-PCR (qPCR) results. Developing and evaluating the stability of reference genes is necessary for studying the molecular mechanisms of M. transitoria in response to drought stress. In this study, 18 candidate reference genes were selected from transcriptome sequencing data of M. transitoria according to their FPKM values under different drought stress degrees. Cluster-23533.34641 was identified as the most stable reference gene for M. transitoria under drought stress based on qPCR results and combined analysis of Genorm, NormFinder, BestKeeper, and Delta Ct algorithms. The reference genes identified in this research offer improved accuracy for quantifying target gene expression in both M. transitoria and Malus species under drought stress. This study could provide insights into the drought stress-related functional gene or factor in M. transitoria, even in Malus species.展开更多
Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving im...Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving immature follicles within living ovaries, has not been extensively explored. This study seeks to establish an efficient method for generating transgenic chickens through ovarian injection, potentially bypassing the challenges associated with primordial germ cell (PGC) manipulation and fertilized egg microinjection. Methods : Hens were anesthetized and underwent a surgical procedure to access the ovary for DNA injection into immature follicles. The study used liposomes to deliver GFP- expressing plasmids at various dosages. After injection, hens recovered, and their eggs were fertilized through artificial insemination. Results : Transgenic chickens were successfully generated in one generation without needing G0 founders. The injection of 20 μg plasmid yielded the highest transgenic efficiency at 12.1%. GFP- positive embryos were confirmed through microscopy, and successful transgene expression was validated at the tissue level using immunostaining. TERT and GFP elements introduced in the G1 generation resulted in 4.1% positive transgene rates, as confirmed by PCR and Southern blotting. Conclusion : This ovarian injection method offers a promising alternative for avian genetic manipulation, bypassing complex PGC procedures and enabling direct generation of G1 transgenic chickens. This technique simplifies the transgenic process for chickens and has the potential to be adapted for other avian species, especially those without established PGCs culture systems.展开更多
Productive tiller number(PTN)is a pivotal trait that significantly influences wheat grain yield.To date,there have been limited reports on the cloning of genes that regulate PTN in wheat.The quantitative trait locus(Q...Productive tiller number(PTN)is a pivotal trait that significantly influences wheat grain yield.To date,there have been limited reports on the cloning of genes that regulate PTN in wheat.The quantitative trait locus(QTL)QPtn.sau-4B,associated with PTN,was previously mapped between the markers KASP-1 and KASP-3 on the chromosome 4B.Here,utilizing 12 newly developed markers and phenotypic data of PTN from recombinants identified within this interval,QPtn.sau-4B was further fine-mapped to a 2.58 Mb interval on wheat chromosome arm 4BS.Within this interval,we identified 14 genes with high-confidence and 32 genes with low-confidence.A 0.17 Mb deletion fragment contained TraesCS4B03G0092600 and TraesCS4B03G0093100,which were assigned as candidate genes for QPtn.sau-4B.Additionally,QPtn.sau-4B had potential to enhance both PTN and grain yield in wheat.Cloning this locus would support the development of wheat cultivars with increased grain yield.展开更多
文摘AIM To investigat the influence of hemochromatosis gene(Hfe) mutation on ^(59)Fe labelled duodenal heme absorption in mice.METHODS Heme absorption was measured in Hfe wild type and Hfe^((-/-)) mice by the duodenal tied loop and by oral gavage methods. The m RNA expression of heme oxygenase(HO-1), Abcg2 and Flvcr1 genes and levels were determined by quantitative polymerase chain reaction.RESULTS Heme absorption was significantly increased in homozygous Hfe^((-/-)) mice despite significant hepatic and splenic iron overload. While duodenal HO-1 mRNA was highly expressed in the wild type and Hfe^((-/-)) heme-treated group following 24 h heme administration, Flvcr1 a mRNA decreased. However, Abcg2 mRNA expression levels in duodenum remained unchanged. CONCLUSION Heme absorption was enhanced in Hfe^((-/-)) mice from both duodenal tied-loop segments and by oral gavage methods. HO-1 m RNA levels were enhanced in mice duodenum after 24 h of heme feeding and may account for enhanced heme absorption in Hfe^((-/-)) mice. Implications for dietary recommendations on heme intake by Hfe subjects to modulate iron loading are important clinical considerations.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
基金Supported by Romanian Ministry of Research,Innovation and Digitization,No.PN23.16.02.04 and No.31PFE/30.12.2021.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.
文摘DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.
基金supported by the National Research Foundation of Korea(RS-2023-00245298)the Korea Healthcare Technology R&D(HI21C1795)grants,funded by the Korean government(to SRK).
文摘A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
文摘Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori-associated diseases is determined by an array of virulence factors. Although extensive studies have been conducted globally, data on the distribution of Helicobacter pylori virulence genes in Libya remain limited, constraining insights into the pathogenicity of local strains and hindering the development of targeted interventions. This study aimed to evaluate the prevalence of H. pylori infection, characterize essential virulence genes [vacA variants (s1/s2, m1/m2), cagA, and iceA1], and examine their association with gastroduodenal diseases among Libyan patients. Gastric biopsies from 144 participants were analyzed using polymerase chain reaction (PCR) assays, and risk factor data were collected via questionnaires. H. pylori was detected in 63.2% of samples by PCR. The vacA gene was present in 84.6% of cases, cagA in 58.2%, and iceA1 in 29.7%. Among vacA variants, s1 allele was most common (53.2%), followed by m1 (42.9%), m2 (37.7%), and s2 (13%) alleles. Significant associations were identified between specific virulence genes and the development of gastroduodenal diseases, highlighting their role in pathogenicity. This investigation is one of Libya’s first comprehensive assessments of H. pylori virulence factors, addressing a critical epidemiological gap. The high prevalence of virulence genes suggests their potential as disease biomarkers. These findings contribute to a deeper understanding of H. pylori pathogenicity within the Libyan population and establish a basis for future clinical interventions and public health strategies to manage and prevent H. pylori-associated diseases in Libya and comparable regions.
基金Supported by Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare,Republic of Korea,No.RS-2022-KH129889.
文摘BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.
基金funded by grants from the National Key R&D Project(2023YFD1400201-02,2023YFD1400203-02)the National Natural Science Foundation of China(31870137)+1 种基金the National Transgenic Research Project(2015ZX08001-002)the Key R&D Project of Guangdong Province(2022B0202060005).
文摘Asian rice comprises two major subspecies:Xian(X)and Geng(G),and the diverged resistance genes(R)have provided a foundation for breeding improved cultivars to control rice blast disease.After conducting two-phase allele mining using six updated FNP marker systems,the functional haplotypes at Pit,Pib,and Pi63 strictly diverged into the X-populations and were defined as X-R loci,while those at Pi54,Pi37,and Pi36 into the G-populations as G-R loci.The genic diversity at the three X-R loci(16 alleles)was twofold higher than that at the three G-R loci(8 alleles),and the allelic diversity in the Southern region(21 alleles)was nearly double that in the Northeastern region(11 alleles).Both observations reflect a significant difference in genetic diversity between X-and G-populations,and indicate that the effective R-genes mainly originated from X-subspecies.Based on the allelic structures characterized by a set of 10 parameters,8 and 16 alleles were respectively recognized as favorable and promising ones for the regional breeding programs.The genotypic structures of the two regional populations were almost different,indicating that the diverged alleles have been further assembled into two series of regional genotypes through long-term breeding programs,despite the presence of one-third of region-common alleles.The genotypic diversity in the Southern region(55 genotypes)was nearly twice as high as that in the Northeastern region(28),which perfectly reflects the aforementioned differences in both genic and allelic diversities.After analyzing the genotypic structures using a set of 13 parameters,4 and 23 genotypes,respectively,can be recommended as the favorable and promising ones for the regional breeding programs.The case study serves as a concrete sample of how to identify the favorable and promising alleles and genotypes,and beneficial parents based their comprehensive population structures for gene-designed breeding.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.
基金Supported by the National Natural Science Foundation of China,No.81973840the Sichuan Provincial Administration of Traditional Chinese Medicine Major Science and Technology projects,No.2021XYCZ004。
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune responses.As a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in HCC.However,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor cells.AIM To investigate the dual-regulation mechanism of cGAS-STING in HCC.METHODS This review was conducted according to the PRISMA guidelines.The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases.Through rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.RESULTS All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 studies.After removing duplicates,remaining 964 records were screened.Ultimately,55 articles met the inclusion criteria and were included in this review.CONCLUSION Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its progression.Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
基金Supported by National Natural Science Foundation of China,No.81770379 and 81470521.
文摘Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.
基金supported by grants from theKey Scientific and Technological Project of Henan Province,China(222102110124)the Joint Fund of Science and Technology Research and Development Plan,Henan Province,China(222103810009)+4 种基金the National Natural Science Foundation of China(32172574,3217180560)the Funding of Joint Research on Agricultural Varieties Improvement of Henan Province,China(2022010503)the Major Science and Technology Project of Henan Province,China(221100110400)the Natural Science Foundation of Henan,China(222300420050)the Science and Technology Innovation Talent Support Program of Henan Province,China(23HASTIT034).
文摘The color and pattern of watermelon rind are crucial external traits that directly affect consumer preferences.Watermelons with stripes having a stronger color than the background rind are ideal for studying stripe patterns in plants,while there is still limited knowledge about the genetic mechanisms underlying stripe coloration due to the lack of germplasm resources.In this study,we focused on a watermelon germplasm with colorless stripes,and genetic analysis revealed that the trait is controlled by a single recessive gene.The gene Clsc(Citrullus lanatus stripe coloration),which is responsible for the colorless stripe,was localized into a 147.6 kb region on Chr9 by linkage analysis in a large F2 mapping population.Further analysis revealed that the Cla97C09G175170 gene encodes the APRR2 transcription factor,plays a crucial role in determining the watermelon colorless stripe phenotype and was deduced to be related to chlorophyll synthesis and chloroplast development.Physiological experiments indicated that Cla97C09G175170 may significantly influence chloroplast development and chlorophyll synthesis in watermelon.The results of this study provide a better understanding of the molecular mechanism of stripe coloration in watermelon and can be useful in the development of marker-assisted selection(MAS)for new watermelon cultivars.
基金supported by the Natural Science Foundation of Qinghai Province(2022-ZJ-902).
文摘The use of a stable reference gene is fundamental for achieving reliable quantitative qRT-PCR (qPCR) results. Developing and evaluating the stability of reference genes is necessary for studying the molecular mechanisms of M. transitoria in response to drought stress. In this study, 18 candidate reference genes were selected from transcriptome sequencing data of M. transitoria according to their FPKM values under different drought stress degrees. Cluster-23533.34641 was identified as the most stable reference gene for M. transitoria under drought stress based on qPCR results and combined analysis of Genorm, NormFinder, BestKeeper, and Delta Ct algorithms. The reference genes identified in this research offer improved accuracy for quantifying target gene expression in both M. transitoria and Malus species under drought stress. This study could provide insights into the drought stress-related functional gene or factor in M. transitoria, even in Malus species.
基金National Key Research and Development Program of China,Grant/Award Number:2023YFF1000204National Natural Science Foundation of China,Grant/Award Number:32172715,32230105 and 32330103+2 种基金The Innovative Project of State Key Laboratory of Animal Biotech Breeding,Grant/Award Number:2024SKLAB1-2/9Chinese Universities Scientific Fund,Grant/Award Number:2024TC167The 2115 Talent Development Program of China Agricultural University。
文摘Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving immature follicles within living ovaries, has not been extensively explored. This study seeks to establish an efficient method for generating transgenic chickens through ovarian injection, potentially bypassing the challenges associated with primordial germ cell (PGC) manipulation and fertilized egg microinjection. Methods : Hens were anesthetized and underwent a surgical procedure to access the ovary for DNA injection into immature follicles. The study used liposomes to deliver GFP- expressing plasmids at various dosages. After injection, hens recovered, and their eggs were fertilized through artificial insemination. Results : Transgenic chickens were successfully generated in one generation without needing G0 founders. The injection of 20 μg plasmid yielded the highest transgenic efficiency at 12.1%. GFP- positive embryos were confirmed through microscopy, and successful transgene expression was validated at the tissue level using immunostaining. TERT and GFP elements introduced in the G1 generation resulted in 4.1% positive transgene rates, as confirmed by PCR and Southern blotting. Conclusion : This ovarian injection method offers a promising alternative for avian genetic manipulation, bypassing complex PGC procedures and enabling direct generation of G1 transgenic chickens. This technique simplifies the transgenic process for chickens and has the potential to be adapted for other avian species, especially those without established PGCs culture systems.
基金supported by National Key Research and Development Program of China(2023YFD1201900)National Nat-ural Science Foundation of China(32472078,31971937)+2 种基金Natural Science Foundation of Sichuan Province(2024NSFSC0312)Crop Characteristic Resources Creation and Utilization Key Laboratory of Sichuan Province(myzdsys24-01)the Key Laboratory of Exploitation and Study of Distinctive Plants in Education Department of Sichuan Province(TSZW2023ZB-10).
文摘Productive tiller number(PTN)is a pivotal trait that significantly influences wheat grain yield.To date,there have been limited reports on the cloning of genes that regulate PTN in wheat.The quantitative trait locus(QTL)QPtn.sau-4B,associated with PTN,was previously mapped between the markers KASP-1 and KASP-3 on the chromosome 4B.Here,utilizing 12 newly developed markers and phenotypic data of PTN from recombinants identified within this interval,QPtn.sau-4B was further fine-mapped to a 2.58 Mb interval on wheat chromosome arm 4BS.Within this interval,we identified 14 genes with high-confidence and 32 genes with low-confidence.A 0.17 Mb deletion fragment contained TraesCS4B03G0092600 and TraesCS4B03G0093100,which were assigned as candidate genes for QPtn.sau-4B.Additionally,QPtn.sau-4B had potential to enhance both PTN and grain yield in wheat.Cloning this locus would support the development of wheat cultivars with increased grain yield.
