Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein ...Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.展开更多
Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies.Histone modifications act as the key factors to modulate the chromatin accessibility.Different histo...Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies.Histone modifications act as the key factors to modulate the chromatin accessibility.Different histone modifications are strongly associated with the localization of chromatin.Heterochromatin primarily localizes at the nuclear periphery,where it interacts with lamina proteins to suppress gene expression.In this review,we summarize the potential bridges that have regulatory functions of histone modifications in chromatin organization and transcriptional regulation at the nuclear periphery.We use lamina-associated domains(LADs)as examples to elucidate the biological roles of the interactions between histone modifications and nuclear lamina in cell differentiation and development.In the end,we highlight the technologies that are currently used to identify and visualize histone modifications and LADs,which could provide spatiotemporal information for understanding their regulatory functions in gene expression and discovering new targets for diseases.展开更多
Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(P...Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.展开更多
The oral microenvironment plays a pivotal role in determining stem cell fate,driving both regeneration and pathological transformation.Emerging evidence suggests that post-translational modifications(PTMs)play a role ...The oral microenvironment plays a pivotal role in determining stem cell fate,driving both regeneration and pathological transformation.Emerging evidence suggests that post-translational modifications(PTMs)play a role as dynamic molecular signatures that regulate key signaling networks in dental-derived mesenchymal stem cells.These PTMs not only influence stem cell self-renewal and differentiation in periodontal tissue regeneration but also contribute to cancer stem cell plasticity and therapeutic resistance in oral squamous cell carcinoma(OSCC).At the pathway level,PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase(p38/c-Jun N-terminal kinase)→runt-related transcription factor 2 in regeneration,whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin,and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition.This review expounds on recent advances in PTM-mediated regulatory mechanisms in dentalderived mesenchymal stem cells,outlines their functional implications in inflammatory and tumor microenvironments,and discusses translational strategies-including localized,time-staged PTM modulation for regeneration and pathwayanchored combinations for OSCC-for regenerative medicine and targeted cancer therapies.Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.展开更多
Infections associated with titanium(Ti)-based implants present significant challenges in clinical treatments,especially when biofilms already form on the implant surface.Many antimicrobial agents,including antibiotics...Infections associated with titanium(Ti)-based implants present significant challenges in clinical treatments,especially when biofilms already form on the implant surface.Many antimicrobial agents,including antibiotics,metallic nanoparticles and antimicrobial peptides,have been extensively used to deal with Ti implant infections.However,these chemical approaches suffer from potential toxicity,antibiotic resistance and poor long-term antibacterial performance.Hence,physical antibacterial surfaces on Ti-based implants have attracted increasing attention.The antibacterial behavior of different surfaces on Ti-based biomaterials against various bacteria only by physical properties of the implants themselves(e.g.,nanotopography)or exogenous physical stimulus(e.g.,photocatalysis)was reviewed,as well as parameters influencing the physical antibacterial processes,such as size,shape and density of the surface nanotextures,and bacterial growth phases.Besides,mechanisms of different fabrication techniques for the physical antibacterial surfaces on Ti-based biomaterials were also summarized.展开更多
The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function a...The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.展开更多
RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.Howe...RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.However,to the best of our knowledge,RNA modifications in peripheral white blood cells(immune cells)have not been systematically investigated before.Here we utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS)for the quantification of 19 chemical modifications in total RNA and 17 chemical modifications in small RNA in peripheral white blood cells from breast cancer patients and healthy controls.We found out 13 RNA modifications were up-regulated in total RNA samples of breast cancer patients.For small RNA samples,only N6-methyladenosine(m^(6)A)was down-regulated in breast cancer patients(P<0.0001).Receiver operating characteristic(ROC)curves analysis showed that N4-acetylcytidine(ac^(4)C)in total RNA had an area under curve(AUC)value of 0.833,and m^(6)A in small RNA had an AUC value of 0.994.Our results further illustrated that RNA modifications may play vital roles in immune cell biology of breast cancer,and may act as novel biomarkers for the diagnosis of breast cancer.展开更多
Magnesium-based solid-state hydrogen storage materials(Mg-HSMs)exhibit significant potential for the global energy transition due to their large hydrogen capacity and energy density.However,their high operating temper...Magnesium-based solid-state hydrogen storage materials(Mg-HSMs)exhibit significant potential for the global energy transition due to their large hydrogen capacity and energy density.However,their high operating temperatures,low operating efficiencies,and short service life have severely hindered largescale applications.To address the above challenges,diverse modification strategies have been proposed.Catalytic modification,achieved by introducing catalysts to enable compositional compounding and structural refinement,enhances surface active site density and bulk hydrogen diffusion pathways,reduces hydrogen dissociation energy barriers,weakens Mg–H bonds,and significantly improves kinetic properties.This approach is considered one of the most effective strategies.However,as research advances,the structures,forms,and catalytic mechanisms of catalysts have become increasingly diverse.Despite progress,challenges such as fragmented research outcomes,inconsistent performance metrics,and an incomplete understanding of structure-property relationships remain unresolved.Therefore,this work systematically summarizes recent advances in catalytic modification strategies for Mg-HSMs,emphasizing the role of catalysts in enhancing reaction kinetics and structural stability,the diversity of catalyst types,forms,and the underlying mechanisms governing catalytic efficacy.Based on critical analysis,this work identifies the current key technical bottlenecks and proposes that the design of next-generation catalysts and the future development of Mg-HSMs should be guided by the principles of‘multiphase heterogeneous interfacial composites'and‘synergistic development',aiming to provide theoretical guidance for the optimization and advancement of their performance.展开更多
The unit cell configuration of lattice structures critically influences their load-bearing and energy absorption performance.In this study,three novel lattice structures were developed by modifying the conventional FB...The unit cell configuration of lattice structures critically influences their load-bearing and energy absorption performance.In this study,three novel lattice structures were developed by modifying the conventional FBCCZ unit cell through reversing,combining,and turning strategies.The designed lattices were fabricated via laser powder bed fusion(LPBF)using Ti-6Al-4V powder,and the mechanical properties,energy absorption capacity,and deformation behaviors were systematically investigated through quasi-static compression tests and finite element simulations.The results demonstrate that the three modified lattices exhibit superior performance over the conventional FBCCZ structure in terms of fracture strain,specific yield strength,specific ultimate strength,specific energy absorption,and energy absorption efficiency,thereby validating the efficacy of unit cell modifications in enhancing lattice performance.Notably,the CFBCCZ and TFBCCZ lattices significantly outperform both the FBCCZ and RFBCCZ lattice structures in load-bearing and energy absorption.While TFBCCZ shows marginally higher specific elastic modulus and energy absorption efficiency than CFBCCZ,the latter achieves superior energy absorption due to its highest ultimate strength and densification strain.Finite element simulations further reveal that the modified lattices,through optimized redistribution and adjustment of internal nodes and struts,effectively alleviate stress concentration during loading.This structural modification enhances the structural integrity and deformation stability under external loads,enabling a synergistic enhancement of load-bearing capacity and energy absorption performance.展开更多
Pectin is a natural polysaccharide with a complex structure consisting of linear and branched regions rich in galacturonic acid.The growing interest in orange peel pectin can be attributed to its abundant supply.Accor...Pectin is a natural polysaccharide with a complex structure consisting of linear and branched regions rich in galacturonic acid.The growing interest in orange peel pectin can be attributed to its abundant supply.According to statistics,about 10 million tons of orange peel waste are produced worldwide each year.Traditionally,the extraction and utilization of pectin have focused on its gelling,thickening,and stabilizing properties in food.However,as more and more research teams have found that pectin has good biocompatibility,biodegradability and easy chemical modification,its potential in drug delivery systems,tissue engineering,and wound healing is gradually being explored.This review focuses on orange peel pectin polysaccharides and discusses its traditional and modern extraction techniques,especially the advanced method of subcritical water extraction.This study also outlines the structural modifications of pectin such as methylation and acetylation,and introduces its antioxidant and anticancer biological activities and their emerging roles in the development of advanced biomaterials such as bone tissue engineering and fibre pad dressings.展开更多
Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologie...Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.展开更多
Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA...Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA methylation,histone modification,noncoding RNA regulation,and chromatin remodeling.Derived from the apical tissues of young permanent teeth,stem cells from apical papilla are odontogenic adult stem cells with high proliferation,self-renewal capacity,and differentiation potential.These cells play crucial roles in root formation and development.This article focuses on the two epigenetic regulatory mechanisms of histone modifications and non-coding RNA.This review summarizes,generalizes,and evaluates the status of research on the epigenetic regulation of the multidirectional differentiation of stem cells from the apical papilla,aiming to explore the mechanisms underlying the multidirectional differentiation process of these stem cells.展开更多
The basic unit of chromatin is the nucleosomal core particle, containing 147 bp of DNA that wraps twice around an octamer of core histones. The core histones bear a highly dynamic N-terminal amino acid tail around 20-...The basic unit of chromatin is the nucleosomal core particle, containing 147 bp of DNA that wraps twice around an octamer of core histones. The core histones bear a highly dynamic N-terminal amino acid tail around 20-35 residues in length and rich in basic amino acids. These tails extending from the surface of nucleosome play an important role in folding of nucleosomal arrays into higher order chromatin structure, which plays an important role in eukaryotic gene regulation. The amino terminal tails protruding from the nuclesomes get modified by the addition of small groups such as methyl, acetyl and phosphoryl groups. In this review, we focus on these complex modi- fication patterns and their biological functions. Moreover, these modifications seem to be part of a complex scheme where distinct histone modifications act in a sequential manner or in combination to form a ＂histone code＂ read by other proteins to control the structure and/or function of the chromatin fiber. Errors in this histone code may be involved in many human diseases especially cancer, the nature of which could be therapeutically exploited. Increasing evidence suggests that many proteins bear multiple, distinct modifications, and the ability of one modification to antagonize or synergize the deposition of another can have significant biological consequences.展开更多
Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at ma...Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and deficiencies.Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease pathogenesis.Notably,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene transcription.This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD.The review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.展开更多
The biosynthesis of prostanoids is involved in both physiological and pathological processes.The expression of prostaglandin-endoperoxide synthase 2(PTGS2;also known as COX-2)has been traditionally associated to the o...The biosynthesis of prostanoids is involved in both physiological and pathological processes.The expression of prostaglandin-endoperoxide synthase 2(PTGS2;also known as COX-2)has been traditionally associated to the onset of several pathologies,from inflammation to cardiovascular,gastrointestinal and oncologic events.For this reason,the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions.In addition to the classic non-steroidal anti-inflammatory drugs,selective and specific PTGS2 inhibitors,termed coxibs,have been generated and widely used.PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1,and it accounts for the elevated prostanoid synthesis that accompanies several pathologies.The main regulation of PTGS2 occurs at the transcription level.In addition to this,the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements,ranging from specificmicroR NAs to proteins that control mR NA degradation.Moreover,the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms.Among these modifications,phosphorylation,glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes.Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress.Finally,these modifications can be used as biomarkers to establish correlations with other parameters,including the immunomodulation dependent on molecular pathological epidemiology determinants,which may provide a better frame for potential therapeutic interventions.展开更多
Single-crystal cathodes(SCCs)are promising substitute materials for polycrystal cathodes(PCCs)in lithium-ion batteries(LIBs),because of their unique ordered structure,excellent cycling stability and high safety perfor...Single-crystal cathodes(SCCs)are promising substitute materials for polycrystal cathodes(PCCs)in lithium-ion batteries(LIBs),because of their unique ordered structure,excellent cycling stability and high safety performance.Cathode materials with layered(LiCoO_(2),LiNi_xCo_yMnzO_(2),LiNi_xCo_yAl_(2)O_(2))and spinel structure(LiMn_(2)O_(4),LiNi_(0.5)Mn_(1.5)O_(4))show a relatively stable electrochemical performance,but still lack of sufficient attention in research field.In this review,we begin with the definition,structural features and electrochemical advantages of SCCs.Common SCCs synthesis methods and the thermodynamic growth mechanism of SCCs with oriented facet exposure are summarized in the following part.Then we introduce the problems and challenges of SCCs faced and the corresponding modification strategies.Finally,the industrialization progress of SCCs is brifly outlined.We intend to tease out the difficulties and advances of SCCs to provide insights for future development of high-performance SCCs for practical LIBs.展开更多
Alzheimer＇s disease （AD）, a fatal, progressive, neurodegener- ative disorder, is the most common cause of old-age demen- tia, accounting for 50-75% of dementia patients. Early stages of AD are marked by vocabulary ...Alzheimer＇s disease （AD）, a fatal, progressive, neurodegener- ative disorder, is the most common cause of old-age demen- tia, accounting for 50-75% of dementia patients. Early stages of AD are marked by vocabulary shrinkage, spatial disori- entation, depression, apraxia, and deterioration of recent forms of declarative memory. In course of time, the patients require close supervision due to the loss of cognitive and functional abilities, and at the terminal stages of the disease, all forms of memory are severely impaired with the patients needing nursing home care （World Alzheimer Report, 2013）.展开更多
Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and b...Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.展开更多
The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain f...The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.展开更多
BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognos...BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.展开更多
基金supported by Applied Basic Research Joint Fund Project of Yunnan Province,No.202301AY070001-200Middle-aged Academic and Technical Training Project for High-Level Talents,No.202105AC160065+1 种基金Yunnan Clinical Medical Center for Neurological and Cardiovascular Diseases,No.YWLCYXZX2023300077Key Clinical Specialty of Neurology in Yunnan Province,No.300064(all to CL)。
文摘Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.
基金financially supported by the National Natural Science Foundation of China(32100450 and 32471370 to Q.P.,12372302 to J.Q.)the Guangdong Pearl River Talent Program(2021QN02Y781 to Q.P.)the Evident&Shenzhen Bay Laboratory Joint Optical Microscopic Imaging Technology Development Program(S234602004-1 to Q.P.).
文摘Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies.Histone modifications act as the key factors to modulate the chromatin accessibility.Different histone modifications are strongly associated with the localization of chromatin.Heterochromatin primarily localizes at the nuclear periphery,where it interacts with lamina proteins to suppress gene expression.In this review,we summarize the potential bridges that have regulatory functions of histone modifications in chromatin organization and transcriptional regulation at the nuclear periphery.We use lamina-associated domains(LADs)as examples to elucidate the biological roles of the interactions between histone modifications and nuclear lamina in cell differentiation and development.In the end,we highlight the technologies that are currently used to identify and visualize histone modifications and LADs,which could provide spatiotemporal information for understanding their regulatory functions in gene expression and discovering new targets for diseases.
文摘Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.
文摘The oral microenvironment plays a pivotal role in determining stem cell fate,driving both regeneration and pathological transformation.Emerging evidence suggests that post-translational modifications(PTMs)play a role as dynamic molecular signatures that regulate key signaling networks in dental-derived mesenchymal stem cells.These PTMs not only influence stem cell self-renewal and differentiation in periodontal tissue regeneration but also contribute to cancer stem cell plasticity and therapeutic resistance in oral squamous cell carcinoma(OSCC).At the pathway level,PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase(p38/c-Jun N-terminal kinase)→runt-related transcription factor 2 in regeneration,whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin,and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition.This review expounds on recent advances in PTM-mediated regulatory mechanisms in dentalderived mesenchymal stem cells,outlines their functional implications in inflammatory and tumor microenvironments,and discusses translational strategies-including localized,time-staged PTM modulation for regeneration and pathwayanchored combinations for OSCC-for regenerative medicine and targeted cancer therapies.Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.
基金National Natural Science Foundation of China(52171114)。
文摘Infections associated with titanium(Ti)-based implants present significant challenges in clinical treatments,especially when biofilms already form on the implant surface.Many antimicrobial agents,including antibiotics,metallic nanoparticles and antimicrobial peptides,have been extensively used to deal with Ti implant infections.However,these chemical approaches suffer from potential toxicity,antibiotic resistance and poor long-term antibacterial performance.Hence,physical antibacterial surfaces on Ti-based implants have attracted increasing attention.The antibacterial behavior of different surfaces on Ti-based biomaterials against various bacteria only by physical properties of the implants themselves(e.g.,nanotopography)or exogenous physical stimulus(e.g.,photocatalysis)was reviewed,as well as parameters influencing the physical antibacterial processes,such as size,shape and density of the surface nanotextures,and bacterial growth phases.Besides,mechanisms of different fabrication techniques for the physical antibacterial surfaces on Ti-based biomaterials were also summarized.
文摘The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.
基金supported by National Natural Science Foundation of China(Nos.21927810,22336004 and 22176167).
文摘RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.However,to the best of our knowledge,RNA modifications in peripheral white blood cells(immune cells)have not been systematically investigated before.Here we utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS)for the quantification of 19 chemical modifications in total RNA and 17 chemical modifications in small RNA in peripheral white blood cells from breast cancer patients and healthy controls.We found out 13 RNA modifications were up-regulated in total RNA samples of breast cancer patients.For small RNA samples,only N6-methyladenosine(m^(6)A)was down-regulated in breast cancer patients(P<0.0001).Receiver operating characteristic(ROC)curves analysis showed that N4-acetylcytidine(ac^(4)C)in total RNA had an area under curve(AUC)value of 0.833,and m^(6)A in small RNA had an AUC value of 0.994.Our results further illustrated that RNA modifications may play vital roles in immune cell biology of breast cancer,and may act as novel biomarkers for the diagnosis of breast cancer.
基金financially supported by the Key Research and Development Projects of Shaanxi Province(Grant Nos.2025CYYBXM-154 and 2024GX-YBXM-213)the Yulin Science and Technology Bureau(Grant Nos.2023-CXY-202 and 2024-CXY-154)+2 种基金the Scientific Research Program Funded by Shaanxi Provincial Education Department(Grant No.23JP008)the Natural Science Foundation of Qinghai Province for Distinguished Young Scholars(Grant No.2025-ZJ-966J)the Talent youth project of Chinese Academy of Sciences(Grant No.E410GC03)。
文摘Magnesium-based solid-state hydrogen storage materials(Mg-HSMs)exhibit significant potential for the global energy transition due to their large hydrogen capacity and energy density.However,their high operating temperatures,low operating efficiencies,and short service life have severely hindered largescale applications.To address the above challenges,diverse modification strategies have been proposed.Catalytic modification,achieved by introducing catalysts to enable compositional compounding and structural refinement,enhances surface active site density and bulk hydrogen diffusion pathways,reduces hydrogen dissociation energy barriers,weakens Mg–H bonds,and significantly improves kinetic properties.This approach is considered one of the most effective strategies.However,as research advances,the structures,forms,and catalytic mechanisms of catalysts have become increasingly diverse.Despite progress,challenges such as fragmented research outcomes,inconsistent performance metrics,and an incomplete understanding of structure-property relationships remain unresolved.Therefore,this work systematically summarizes recent advances in catalytic modification strategies for Mg-HSMs,emphasizing the role of catalysts in enhancing reaction kinetics and structural stability,the diversity of catalyst types,forms,and the underlying mechanisms governing catalytic efficacy.Based on critical analysis,this work identifies the current key technical bottlenecks and proposes that the design of next-generation catalysts and the future development of Mg-HSMs should be guided by the principles of‘multiphase heterogeneous interfacial composites'and‘synergistic development',aiming to provide theoretical guidance for the optimization and advancement of their performance.
基金supported by National Key Lab of Aerospace Power System and Plasma Technology Foundation of China(Grant No.APSPT202301002)National Natural Science Foundation of China(Grant No.52001038)Natural Science Foundation of Chongqing,China(Grant Nos.cstc2019jcyj-msxm X0787 and cstc2021jcyj-msxm X0011)。
文摘The unit cell configuration of lattice structures critically influences their load-bearing and energy absorption performance.In this study,three novel lattice structures were developed by modifying the conventional FBCCZ unit cell through reversing,combining,and turning strategies.The designed lattices were fabricated via laser powder bed fusion(LPBF)using Ti-6Al-4V powder,and the mechanical properties,energy absorption capacity,and deformation behaviors were systematically investigated through quasi-static compression tests and finite element simulations.The results demonstrate that the three modified lattices exhibit superior performance over the conventional FBCCZ structure in terms of fracture strain,specific yield strength,specific ultimate strength,specific energy absorption,and energy absorption efficiency,thereby validating the efficacy of unit cell modifications in enhancing lattice performance.Notably,the CFBCCZ and TFBCCZ lattices significantly outperform both the FBCCZ and RFBCCZ lattice structures in load-bearing and energy absorption.While TFBCCZ shows marginally higher specific elastic modulus and energy absorption efficiency than CFBCCZ,the latter achieves superior energy absorption due to its highest ultimate strength and densification strain.Finite element simulations further reveal that the modified lattices,through optimized redistribution and adjustment of internal nodes and struts,effectively alleviate stress concentration during loading.This structural modification enhances the structural integrity and deformation stability under external loads,enabling a synergistic enhancement of load-bearing capacity and energy absorption performance.
文摘Pectin is a natural polysaccharide with a complex structure consisting of linear and branched regions rich in galacturonic acid.The growing interest in orange peel pectin can be attributed to its abundant supply.According to statistics,about 10 million tons of orange peel waste are produced worldwide each year.Traditionally,the extraction and utilization of pectin have focused on its gelling,thickening,and stabilizing properties in food.However,as more and more research teams have found that pectin has good biocompatibility,biodegradability and easy chemical modification,its potential in drug delivery systems,tissue engineering,and wound healing is gradually being explored.This review focuses on orange peel pectin polysaccharides and discusses its traditional and modern extraction techniques,especially the advanced method of subcritical water extraction.This study also outlines the structural modifications of pectin such as methylation and acetylation,and introduces its antioxidant and anticancer biological activities and their emerging roles in the development of advanced biomaterials such as bone tissue engineering and fibre pad dressings.
基金supported by the National Natural Science Foundation of China(Nos.82271158,82301312,82071045,82101219,82071048).
文摘Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.
文摘Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA methylation,histone modification,noncoding RNA regulation,and chromatin remodeling.Derived from the apical tissues of young permanent teeth,stem cells from apical papilla are odontogenic adult stem cells with high proliferation,self-renewal capacity,and differentiation potential.These cells play crucial roles in root formation and development.This article focuses on the two epigenetic regulatory mechanisms of histone modifications and non-coding RNA.This review summarizes,generalizes,and evaluates the status of research on the epigenetic regulation of the multidirectional differentiation of stem cells from the apical papilla,aiming to explore the mechanisms underlying the multidirectional differentiation process of these stem cells.
文摘The basic unit of chromatin is the nucleosomal core particle, containing 147 bp of DNA that wraps twice around an octamer of core histones. The core histones bear a highly dynamic N-terminal amino acid tail around 20-35 residues in length and rich in basic amino acids. These tails extending from the surface of nucleosome play an important role in folding of nucleosomal arrays into higher order chromatin structure, which plays an important role in eukaryotic gene regulation. The amino terminal tails protruding from the nuclesomes get modified by the addition of small groups such as methyl, acetyl and phosphoryl groups. In this review, we focus on these complex modi- fication patterns and their biological functions. Moreover, these modifications seem to be part of a complex scheme where distinct histone modifications act in a sequential manner or in combination to form a ＂histone code＂ read by other proteins to control the structure and/or function of the chromatin fiber. Errors in this histone code may be involved in many human diseases especially cancer, the nature of which could be therapeutically exploited. Increasing evidence suggests that many proteins bear multiple, distinct modifications, and the ability of one modification to antagonize or synergize the deposition of another can have significant biological consequences.
基金Supported by The National Institute of Alcohol Abuse and Alcoholism grants AA014371 (to Joshi-Barve S),AA015970 (to McClain CJ), and Office of Dietary Supplements, NIH
文摘Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and deficiencies.Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease pathogenesis.Notably,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene transcription.This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD.The review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.
基金Supported by Ministerio de Ciencia Innovación y Universidades,No.SAF2017-82436R and SAF2016-75004RComunidad de Madrid,No.S2017/BMD-3686+2 种基金Fundación Ramón Areces,No.2016/CIVP18A3864Instituto de Salud CarlosⅢby Fondos FEDER,No.Cibercv and Ciberehd
文摘The biosynthesis of prostanoids is involved in both physiological and pathological processes.The expression of prostaglandin-endoperoxide synthase 2(PTGS2;also known as COX-2)has been traditionally associated to the onset of several pathologies,from inflammation to cardiovascular,gastrointestinal and oncologic events.For this reason,the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions.In addition to the classic non-steroidal anti-inflammatory drugs,selective and specific PTGS2 inhibitors,termed coxibs,have been generated and widely used.PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1,and it accounts for the elevated prostanoid synthesis that accompanies several pathologies.The main regulation of PTGS2 occurs at the transcription level.In addition to this,the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements,ranging from specificmicroR NAs to proteins that control mR NA degradation.Moreover,the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms.Among these modifications,phosphorylation,glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes.Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress.Finally,these modifications can be used as biomarkers to establish correlations with other parameters,including the immunomodulation dependent on molecular pathological epidemiology determinants,which may provide a better frame for potential therapeutic interventions.
基金supported by the National Natural Science Foundation of China(52001171,21835004,51901104,22020102002,51801105 and 52101226)the National Key R&D Program of China(2017YFA0206700 and 2018YFB1502101)+1 种基金the NCC Fund(NCC2020FH03)the 111 Project from the Ministry of Education of China(B12015)。
文摘Single-crystal cathodes(SCCs)are promising substitute materials for polycrystal cathodes(PCCs)in lithium-ion batteries(LIBs),because of their unique ordered structure,excellent cycling stability and high safety performance.Cathode materials with layered(LiCoO_(2),LiNi_xCo_yMnzO_(2),LiNi_xCo_yAl_(2)O_(2))and spinel structure(LiMn_(2)O_(4),LiNi_(0.5)Mn_(1.5)O_(4))show a relatively stable electrochemical performance,but still lack of sufficient attention in research field.In this review,we begin with the definition,structural features and electrochemical advantages of SCCs.Common SCCs synthesis methods and the thermodynamic growth mechanism of SCCs with oriented facet exposure are summarized in the following part.Then we introduce the problems and challenges of SCCs faced and the corresponding modification strategies.Finally,the industrialization progress of SCCs is brifly outlined.We intend to tease out the difficulties and advances of SCCs to provide insights for future development of high-performance SCCs for practical LIBs.
基金in part supported by the German Ministry for Education and Research (BMBF) special network program KMU-Innovativ-2
文摘Alzheimer＇s disease （AD）, a fatal, progressive, neurodegener- ative disorder, is the most common cause of old-age demen- tia, accounting for 50-75% of dementia patients. Early stages of AD are marked by vocabulary shrinkage, spatial disori- entation, depression, apraxia, and deterioration of recent forms of declarative memory. In course of time, the patients require close supervision due to the loss of cognitive and functional abilities, and at the terminal stages of the disease, all forms of memory are severely impaired with the patients needing nursing home care （World Alzheimer Report, 2013）.
基金supported by the National Natural Science Foundation of China(32061143005,32170313,and 32100266)Shandong Provincial Natural Science Foundation(ZR2021QC022 and ZR2022QC059).
文摘Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.
基金supported by the Natural Science Foundation Project of China(81820108015,82201683)China Postdoctoral Science Foundation(2021M693926,2020TQ0393,2020M683634XB)+1 种基金Chongqing Science&Technology Commission(cstc2021jcyj-bshX0150,cstc2021jcyj-bshX0201)Special Funding for Chongqing Postdoctoral Research Projects(2021XMT001)。
文摘The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.
文摘BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.
